Nanoparticles and targeted drug delivery in cancer therapy

Immunology Letters - Tập 190 - Trang 64-83 - 2017
Behdokht Bahrami1,2, Mohammad Hojjat-Farsangi3,4, Hamed Mohammadi5,6, Enayat Anvari7, Ghasem Ghalamfarsa8, Mehdi Yousefi6,9, Farhad Jadidi-Niaragh5,6,10
1Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3Department of Oncology-Pathology, Immune and Gene therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden
4Department of Immunology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
5Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
7Department of physiology, Faculty of Medicine, Ilam University Of Medical Sciences, Ilam, Iran
8Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
9Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
10Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Tài liệu tham khảo

Farokhzad, 2009, Impact of nanotechnology on drug delivery, ACS Nano, 3, 16, 10.1021/nn900002m Petros, 2010, Strategies in the design of nanoparticles for therapeutic applications, Nat. Rev. Drug Discov., 9, 615, 10.1038/nrd2591 Zhang, 2010, Host- guest interaction mediated polymeric assemblies: multifunctional nanoparticles for drug and gene delivery, ACS Nano, 4, 1049, 10.1021/nn901213a Bombelli, 2014, The scope of nanoparticle therapies for future metastatic melanoma treatment, Lancet Oncol., 15, e22, 10.1016/S1470-2045(13)70333-4 Qi, 2014, Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor, Nanoscale Res. Lett., 9, 1, 10.1186/1556-276X-9-595 2008, Nanoparticles for Drug Delivery in Cancer Treatment. Urologic Oncology: Seminars and Original Investigations Jadidi-Niaragh, 2017, CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice, J. Control. Release, 246, 46, 10.1016/j.jconrel.2016.12.012 Choi, 2007, Renal clearance of quantum dots, Nat. Biotechnol., 25, 1165, 10.1038/nbt1340 Najafi-Hajivar, 2016, Overview on experimental models of interactions between nanoparticles and the immune system, Biomed. Pharmacother., 83, 1365, 10.1016/j.biopha.2016.08.060 Davis, 2008, Nanoparticle therapeutics: an emerging treatment modality for cancer, Nat. Rev. Drug Discov., 7, 771, 10.1038/nrd2614 Decuzzi, 2009, Intravascular delivery of particulate systems: does geometry really matter?, Pharm. Res., 26, 235, 10.1007/s11095-008-9697-x Perrault, 2009, Mediating tumor targeting efficiency of nanoparticles through design, Nano Lett., 9, 1909, 10.1021/nl900031y Kim, 2010, In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages, ACS Nano, 4, 4559, 10.1021/nn100736c Hawker, 2005, The convergence of synthetic organic and polymer chemistries, Science, 309, 1200, 10.1126/science.1109778 Johnson, 1969, Potassium permeability of single compartment liposomes with and without valinomycin, Biochim. et Biophys. Acta (BBA): Biomembr., 193, 82, 10.1016/0005-2736(69)90061-3 Malam, 2009, Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer, Trends Pharmacol. Sci., 30, 592, 10.1016/j.tips.2009.08.004 Torchilin, 2005, Recent advances with liposomes as pharmaceutical carriers, Nat. Rev. Drug Discov., 4, 145, 10.1038/nrd1632 Hu, 2010, Half-antibody functionalized lipid- polymer hybrid nanoparticles for targeted drug delivery to carcinoembryonic antigen presenting pancreatic cancer cells, Mol. Pharm., 7, 914, 10.1021/mp900316a Misra, 2010, Cancer nanotechnology: application of nanotechnology in cancer therapy, Drug Discov. Today, 15, 842, 10.1016/j.drudis.2010.08.006 Doktorovova, 2014, Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers–a systematic review of in vitro data, Eur. J. Pharm. Biopharm., 87, 1, 10.1016/j.ejpb.2014.02.005 Selvamuthukumar, 2012, Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy, Lipids Health Dis., 11, 159, 10.1186/1476-511X-11-159 Shao, 2015, Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA, Int. J. Nanomed., 10, 1223, 10.2147/IJN.S77837 Müller, 1995, Solid lipid nanoparticles (SLN): an alternative colloidal carrier system for controlled drug delivery, Eur. J. Pharm. Biopharm., 41, 62 Wong, 2007, Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles, Adv. Drug Deliv. Rev., 59, 491, 10.1016/j.addr.2007.04.008 Acharya, 2011, PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect, Adv. Drug Deliv. Rev., 63, 170, 10.1016/j.addr.2010.10.008 Astruc, 2010, Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine, Chem. Rev., 110, 1857, 10.1021/cr900327d Tomalia, 1998 Hawker, 1990, Preparation of polymers with controlled molecular architecture: a new convergent approach to dendritic macromolecules, J. Am. Chem. Soc., 112, 7638, 10.1021/ja00177a027 Svenson, 2005, Dendrimers in biomedical applications—reflections on the field, Adv. Drug Deliv. Rev., 57, 2106, 10.1016/j.addr.2005.09.018 Turrin, 2011, Dendrimers for imaging. dendrimers: towards catalytic, Mater. Biomed. Uses, 393 Menjoge, 2010, Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications, Drug Discov. Today, 15, 171, 10.1016/j.drudis.2010.01.009 Peng, 2008, Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy, Int. J. Nanomed., 3, 311 Yu, 2008, Drug-loaded superparamagnetic iron oxide nanoparticles for combined cancer imaging and therapy in vivo, Angew. Chem. Int. Ed., 47, 5362, 10.1002/anie.200800857 Sun, 2010, PEG-mediated synthesis of highly dispersive multifunctional superparamagnetic nanoparticles: their physicochemical properties and function in vivo, ACS Nano, 4, 2402, 10.1021/nn100190v Kievit, 2011, Surface engineering of iron oxide nanoparticles for targeted cancer therapy, Acc. Chem. Res., 44, 853, 10.1021/ar2000277 Eigler, 1990, Positioning single atoms with a scanning tunnelling microscope, Nature, 344, 524, 10.1038/344524a0 Park, 2008, Micellar hybrid nanoparticles for simultaneous magnetofluorescent imaging and drug delivery, Angew. Chem., 120, 7394, 10.1002/ange.200801810 Libutti, 2009 Blasiak, 2013, Applications of nanoparticles for MRI cancer diagnosis and therapy, J. Nanomater., 2013, 12, 10.1155/2013/148578 Yameen, 2014, Insight into nanoparticle cellular uptake and intracellular targeting, J. Control. Release, 190, 485, 10.1016/j.jconrel.2014.06.038 Xiang, 2012, Uptake mechanisms of non-viral gene delivery, J. Control. Release, 158, 371, 10.1016/j.jconrel.2011.09.093 Zappavigna, 2016, Nanocarriers conjugated with cell penetrating peptides: new trojan horses by modern ulysses, Curr. Pharm. Biotechnol., 17, 700, 10.2174/1389201017666160415155145 Sahay, 2010, Endocytosis of nanomedicines, J. Control. Release, 145, 182, 10.1016/j.jconrel.2010.01.036 Rappoport, 2008, Focusing on clathrin-mediated endocytosis, Biochem. J, 412, 415, 10.1042/BJ20080474 Pucadyil, 2009, Conserved functions of membrane active GTPases in coated vesicle formation, Science, 325, 1217, 10.1126/science.1171004 Vogel, 1998, Expression of caveolin-1 and polarized formation of invaginated caveolae in Caco-2 and MDCK II cells, J. Cell Sci., 111, 825, 10.1242/jcs.111.6.825 Qaddoumi, 2004, The characteristics and mechanisms of uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell layers, Pharm. Res., 21, 641, 10.1023/B:PHAM.0000022411.47059.76 Nan, 2008, Cellular uptake and cytotoxicity of silica nanotubes, Nano Lett., 8, 2150, 10.1021/nl0802741 Ma, 2003, Uptake of chitosan and associated insulin in Caco-2 cell monolayers: a comparison between chitosan molecules and chitosan nanoparticles, Pharm. Res., 20, 1812, 10.1023/B:PHAM.0000003379.76417.3e Tekle, 2008, Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands, Nano Lett., 8, 1858, 10.1021/nl0803848 Medina-Kauwe, 2007, Alternative endocytic mechanisms exploited by pathogens: new avenues for therapeutic delivery?, Adv. Drug Deliv. Rev., 59, 798, 10.1016/j.addr.2007.06.009 Parton, 2007, The multiple faces of caveolae, Nat. Rev. Mol. Cell Biol., 8, 185, 10.1038/nrm2122 Perumal, 2008, The effect of surface functionality on cellular trafficking of dendrimers, Biomaterials, 29, 3469, 10.1016/j.biomaterials.2008.04.038 Benmerah, 2007, Clathrin‐Coated Pits: Vive La Différence?, Traffic, 8, 970, 10.1111/j.1600-0854.2007.00585.x Haigler, 1979, Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor, J. Cell Biol., 83, 82, 10.1083/jcb.83.1.82 Kou, 2013, The endocytosis and intracellular fate of nanomedicines: implication for rational design, Asian J. Pharm. Sci., 8, 1, 10.1016/j.ajps.2013.07.001 Mayor, 2007, Pathways of clathrin-independent endocytosis, Nat. Rev. Mol. Cell Biol., 8, 603, 10.1038/nrm2216 Mercer, 2009, Virus entry by macropinocytosis, Nat. Cell Biol., 11, 510, 10.1038/ncb0509-510 Nam, 2009, Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles, J. Control. Release, 135, 259, 10.1016/j.jconrel.2009.01.018 Bertrand, 2012, The journey of a drug-carrier in the body: an anatomo-physiological perspective, J. Control. Release, 161, 152, 10.1016/j.jconrel.2011.09.098 Prabhu, 2015, Polymeric nanoparticles for targeted treatment in oncology: current insights, Int. J. Nanomed., 10, 1001 Sinha, 2006, Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery, Mol. Cancer Ther., 5, 1909, 10.1158/1535-7163.MCT-06-0141 Smith, 2008, Bioconjugated quantum dots for in vivo molecular and cellular imaging, Adv. Drug Deliv. Rev., 60, 1226, 10.1016/j.addr.2008.03.015 Ferreira, 2013, pH-sensitive liposomes for drug delivery in cancer treatment, Therap. Deliv., 4, 1099, 10.4155/tde.13.80 Bae, 2011, Targeted drug delivery to tumors: myths, reality and possibility, J. Control. Release, 153, 198, 10.1016/j.jconrel.2011.06.001 Danhier, 2010, To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery, J. Control. Release, 148, 135, 10.1016/j.jconrel.2010.08.027 Choi, 2010, Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles, Proc. Natl. Acad. Sci., 107, 1235, 10.1073/pnas.0914140107 Georgieva, 2014, Smuggling drugs into the brain: an overview of ligands targeting transcytosis for drug delivery across the blood–brain barrier, Pharmaceutics, 6, 557, 10.3390/pharmaceutics6040557 Li, 2010, Binding and uptake of H-ferritin are mediated by human transferrin receptor-1, Proc. Natl. Acad. Sci., 107, 3505, 10.1073/pnas.0913192107 Trinder, 2003, Transferrin receptor 2: a new molecule in iron metabolism, Int. J. Biochem. Cell Biol., 35, 292, 10.1016/S1357-2725(02)00258-3 Gray, 2013, From phage display to nanoparticle delivery: functionalizing liposomes with multivalent peptides improves targeting to a cancer biomarker, Bioconjugate Chem., 24, 85, 10.1021/bc300498d Daniels, 2012, The transferrin receptor and the targeted delivery of therapeutic agents against cancer, Biochim. et Biophys. Acta (BBA): Gen. Subj., 1820, 291, 10.1016/j.bbagen.2011.07.016 Qian, 2002, Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway, Pharmacol. Rev., 54, 561, 10.1124/pr.54.4.561 Zhao, 2014, Transferrin conjugated poly (γ-glutamic acid-maleimide-co-l-lactide)-1, 2-dipalmitoylsn-glycero-3-phosphoethanolamine copolymer nanoparticles for targeting drug delivery, Colloids Surf. B: Biointerfaces, 123, 787, 10.1016/j.colsurfb.2014.10.024 Ren, 2010, Development of transferrin functionalized poly (ethylene glycol)/poly (lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma, J. Mater. Sci., 21, 2673 Ding, 2013, Immobilized transferrin Fe3O4@ SiO2 nanoparticle with high doxorubicin loading for dual-targeted tumor drug delivery, Int. J. Nanomed., 8, 4631 Malarvizhi, 2014, Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma, Nanomed.: Nanotechnol. Biol. Med., 10, 1649, 10.1016/j.nano.2014.05.011 Guo, 2015, Transferrin-conjugated doxorubicin-loaded lipid-coated nanoparticles for the targeting and therapy of lung cancer, Oncol. Lett., 9, 1065, 10.3892/ol.2014.2840 Bao, 2015, Plga-Pll-Peg-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway, Int. J. Nanomed., 10, 557 Koppu, 2010, Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA, J. Control. Release, 143, 215, 10.1016/j.jconrel.2009.11.015 Han, 2010, Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors, Mol. Pharm., 7, 2156, 10.1021/mp100185f Ghalamfarsa, 2016, Application of nanomedicine for crossing the blood–brain barrier: theranostic opportunities in multiple sclerosis, J. Immunotoxicol., 13, 603, 10.3109/1547691X.2016.1159264 Jiang, 2012, Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model, PLoS One, 7, e37376, 10.1371/journal.pone.0037376 Porru, 2014, Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid, Oncotarget, 5, 10446, 10.18632/oncotarget.2182 Kopecka, 2016, Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors, Oncotarget, 7, 20753, 10.18632/oncotarget.8012 Salzano, 2011, Self-assembly nanoparticles for the delivery of bisphosphonates into tumors, Int. J. Pharm., 403, 292, 10.1016/j.ijpharm.2010.10.046 Agrati, 2011, Multicompartment vectors as novel drug delivery systems: selective activation of Tγδ lymphocytes after zoledronic acid delivery, Nanomed. Nanotechnol. Biol. Med., 7, 153, 10.1016/j.nano.2010.10.003 Kopecka, 2015, Self-assembling nanoparticles encapsulating zoledronic acid revert multidrug resistance in cancer cells, Oncotarget, 6, 31461, 10.18632/oncotarget.5058 Marra, 2012, New self-assembly nanoparticles and stealth liposomes for the delivery of zoledronic acid: a comparative study, Biotechnol. Adv., 30, 302, 10.1016/j.biotechadv.2011.06.018 Dixit, 2015, Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors, Nanoscale, 7, 1782, 10.1039/C4NR04853A Ulbrich, 2009, Transferrin-and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood?brain barrier (BBB), Eur. J. Pharm. Biopharm., 71, 251, 10.1016/j.ejpb.2008.08.021 Korkusuz, 2013, Transferrin-coated gadolinium nanoparticles as MRI contrast agent, Mol. Imaging Biol., 15, 148, 10.1007/s11307-012-0579-6 Eavarone, 2000, Targeted drug delivery to C6 glioma by transferrin-coupled liposomes, J. Biomed. Mater. Res., 51, 10, 10.1002/(SICI)1097-4636(200007)51:1<10::AID-JBM2>3.0.CO;2-R Gupta, 2007, Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain, J. Pharm. Pharmacol., 59, 935, 10.1211/jpp.59.7.0004 Xu, 2002, Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery, Hum. Gene Ther., 13, 469, 10.1089/10430340252792594 Zhang, 2009, Transferrin receptor targeted lipopolyplexes for delivery of antisense oligonucleotide g3139 in a murine k562 xenograft model, Pharm. Res., 26, 1516, 10.1007/s11095-009-9864-8 Chiu, 2014, Improving the systemic drug delivery efficacy of nanoparticles using a transferrin variant for targeting, J. Control. Release, 180, 33, 10.1016/j.jconrel.2014.01.027 Yoon, 2009, Genetically engineering transferrin to improve its in vitro ability to deliver cytotoxins, J. Control. Release, 133, 178, 10.1016/j.jconrel.2008.10.006 Yoon, 2010, Intratumoral therapy of glioblastoma multiforme using genetically engineered transferrin for drug delivery, Cancer Res., 70, 4520, 10.1158/0008-5472.CAN-09-4311 Hu, 2009, Lactoferrin-conjugated PEG–PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations, J. Control. Release, 134, 55, 10.1016/j.jconrel.2008.10.016 Davis, 2009, The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic, Mol. Pharm., 6, 659, 10.1021/mp900015y Elliott, 1997, Intercellular trafficking and protein delivery by a herpesvirus structural protein, Cell, 88, 223, 10.1016/S0092-8674(00)81843-7 Frankel, 1988, Cellular uptake of the tat protein from human immunodeficiency virus, Cell, 55, 1189, 10.1016/0092-8674(88)90263-2 Koren, 2012, Cell-penetrating peptides: breaking through to the other side, Trends Mol. Med., 18, 385, 10.1016/j.molmed.2012.04.012 Milletti, 2012, Cell-penetrating peptides: classes, origin, and current landscape, Drug Discov. Today, 17, 850, 10.1016/j.drudis.2012.03.002 Madani, 2011, Mechanisms of cellular uptake of cell-penetrating peptides, J. Biophys., 2011, 10.1155/2011/414729 Vasconcelos, 2015, Conjugation of cell-penetrating peptides with poly (lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery, Int. J. Nanomed., 10, 609 Derossi, 1994, The third helix of the Antennapedia homeodomain translocates through biological membranes, J. Biol. Chem., 269, 10444, 10.1016/S0021-9258(17)34080-2 Torchilin, 2008, Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers, Adv. Drug Deliv. Rev., 60, 548, 10.1016/j.addr.2007.10.008 Josephson, 1999, High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates, Bioconjugate Chem., 10, 186, 10.1021/bc980125h Heitz, 2009, Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics, Br. J. Pharmacol., 157, 195, 10.1111/j.1476-5381.2009.00057.x Kaufman, 2003, Superparamagnetic iron oxide particles transactivator protein-fluorescein isothiocyanate particle labeling for in vivo magnetic resonance imaging detection of cell migration: uptake and durability, Transplantation, 76, 1043, 10.1097/01.TP.0000090164.42732.47 Harris, 2008, Protease-triggered unveiling of bioactive nanoparticles, Small, 4, 1307, 10.1002/smll.200701319 Wen, 2014 Asai, 2014, Cell-penetrating peptide-conjugated lipid nanoparticles for siRNA delivery, Biochem. Biophys. Res. Commun., 444, 599, 10.1016/j.bbrc.2014.01.107 Torchilin, 2003, Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes, Proc. Natl. Acad. Sci., 100, 1972, 10.1073/pnas.0435906100 Pappalardo, 2014, In vitro transfection of bone marrow-derived dendritic cells with TATp-liposomes, Int. J. Nanomed., 9, 963, 10.2147/IJN.S53432 Fu, 2015, Tumor-targeted paclitaxel delivery and enhanced penetration using TAT-decorated liposomes comprising redox-responsive poly (Ethylene glycol), J. Pharm. Sci., 104, 1160, 10.1002/jps.24291 Jiang, 2012, Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery, Biomaterials, 33, 9246, 10.1016/j.biomaterials.2012.09.027 Balzeau, 2013, The effect of functionalizing lipid nanocapsules with NFL-TBS: 40–63 peptide on their uptake by glioblastoma cells, Biomaterials, 34, 3381, 10.1016/j.biomaterials.2013.01.068 Yang, 2015, Photo-responsive and NGR-mediated multifunctional nanostructured lipid carrier for tumor-specific therapy, J. Pharm. Sci., 104, 1328, 10.1002/jps.24333 Cryan, 2006, Increased intracellular targeting to airway cells using octaarginine-coated liposomes: in vitro assessment of their suitability for inhalation, Mol. Pharm., 3, 104, 10.1021/mp050070i Patlolla, 2010, Translocation of cell penetrating peptide engrafted nanoparticles across skin layers, Biomaterials, 31, 5598, 10.1016/j.biomaterials.2010.03.010 Sethuraman, 2008, A biodegradable pH-sensitive micelle system for targeting acidic solid tumors, Pharm. Res., 25, 657, 10.1007/s11095-007-9480-4 Torchilin, 2001, TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors, Proc. Natl. Acad. Sci., 98, 8786, 10.1073/pnas.151247498 Rudolph, 2012, Formation of solid lipid nanoparticle (SLN)–gene vector complexes for transfection of mammalian cells in vitro, Cold Spring Harb. Protoc., 2012, 10.1101/pdb.prot068122 Liu, 2015, Multifunctional tandem peptide modified paclitaxel loaded liposomes for the treatment of vasculogenic mimicry and cancer stem cells in malignant glioma, ACS Appl. Mater. Interfaces Yuan, 2015, Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma, Drug Deliv., 1, 10.3109/10717544.2015.1040527 Zheng, 2015, Transferrin and cell-penetrating peptide dual-functioned liposome for targeted drug delivery to glioma, Int. J. Clin. Exp. Med., 8, 1658 Liu, 2010, Cellular internalization of quantum dots noncovalently conjugated with arginine-rich cell-penetrating peptides, J. Nanosci. Nanotechnol., 10, 6534, 10.1166/jnn.2010.2637 Liu, 2013, Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides, Colloids Surf. B: Biointerfaces, 111, 162, 10.1016/j.colsurfb.2013.05.038 Stroh, 2005, Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo, Nat. Med., 11, 678, 10.1038/nm1247 Li, 2014, Enzyme-responsive cell-penetrating peptide conjugated mesoporous silica quantum dot nanocarriers for controlled release of nucleus-targeted drug molecules and real-time intracellular fluorescence imaging of tumor cells, Adv. Healthcare Mater., 3, 1230, 10.1002/adhm.201300613 Park, 2014, Cell-selective intracellular drug delivery using doxorubicin and α-helical peptides conjugated to gold nanoparticles, Biomaterials, 35, 3480, 10.1016/j.biomaterials.2013.12.094 Dekiwadia, 2012, Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes, J. Pept. Sci., 18, 527, 10.1002/psc.2430 de la Fuente, 2005, Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus, Bioconjugate Chem., 16, 1176, 10.1021/bc050033+ Yuan, 2012, TAT peptide-functionalized gold nanostars: enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance, J. Am. Chem. Soc., 134, 11358, 10.1021/ja304180y Winer, 2010, F3-targeted cisplatin-hydrogel nanoparticles as an effective therapeutic that targets both murine and human ovarian tumor endothelial cells in vivo, Cancer Res., 70, 8674, 10.1158/0008-5472.CAN-10-1917 Lee, 2011, Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy, Int. J. Cancer, 128, 2470, 10.1002/ijc.25578 Malhotra, 2013, Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA delivery targeting neurodegenerative diseases, Biomaterials, 34, 1270, 10.1016/j.biomaterials.2012.10.013 Egusquiaguirre, 2015, Development of surface modified biodegradable polymeric nanoparticles to deliver GSE24: 2 peptide to cells: a promising approach for the treatment of defective telomerase disorders, Eur. J. Pharm. Biopharm., 91, 91, 10.1016/j.ejpb.2015.01.028 Siahmansouri, 2016, Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line, J. Pharm. Pharmacol., 68, 1119, 10.1111/jphp.12593 Qin, 2011, Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery, Int. J. Pharm., 419, 85, 10.1016/j.ijpharm.2011.07.021 Cheng, 2014, Blood-Brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging, Small, 10, 5137 Lee, 2011, A gene delivery system for human cells mediated by both a cell-penetrating peptide and a piggyBac transposase, Biomaterials, 32, 6264, 10.1016/j.biomaterials.2011.05.012 Shin, 2014, Cell-penetrating peptides: achievements and challenges in application for cancer treatment, J. Biomed. Mater. Res. A, 102, 575, 10.1002/jbm.a.34859 Meade, 2007, Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides, Adv. Drug Deliv. Rev., 59, 134, 10.1016/j.addr.2007.03.004 Park, 2005, Nontoxic membrane translocation peptide from protamine, low molecular weight protamine (LMWP), for enhanced intracellular protein delivery: in vitro and in vivo study, FASEB J., 19, 1555, 10.1096/fj.04-2322fje Järver, 2010, In vivo biodistribution and efficacy of peptide mediated delivery, Trends Pharmacol. Sci., 31, 528, 10.1016/j.tips.2010.07.006 Rousselle, 2001, Enhanced delivery of doxorubicin into the brain via a peptide-vector-mediated strategy: saturation kinetics and specificity, J. Pharmacol. Exp. Ther., 296, 124 Prassl, 2009, Molecular structure of low density lipoprotein: current status and future challenges, Eur. Biophys. J., 38, 145, 10.1007/s00249-008-0368-y Firestone, 1994, Low-density lipoprotein as a vehicle for targeting antitumor compounds to cancer cells, Bioconjugate Chem., 5, 105, 10.1021/bc00026a002 Zheng, 2005, Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents, Proc. Natl. Acad. Sci. U. S. A., 102, 17757, 10.1073/pnas.0508677102 Harisa, 2014, Low density lipoprotein bionanoparticles: from cholesterol transport to delivery of anti-cancer drugs, Saudi Pharm. J., 22, 504, 10.1016/j.jsps.2013.12.015 Shaw, 1991 Glickson, 2008, Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents, Mol. Imaging, 7, 101, 10.2310/7290.2008.0012 Corbin, 2007, Mimicking nature's nanocarrier: synthetic low-density lipoprotein-like nanoparticles for cancer-drug delivery, Nanomedicine (Lond.), 10.2217/17435889.2.3.375 Chu, 2001, Low density lipoprotein as a targeted carrier for doxorubicin in nude mice bearing human hepatoma HepG2 cells, Life Sci., 70, 591, 10.1016/S0024-3205(01)01441-2 Berg, 2005, Porphyrin-related photosensitizers for cancer imaging and therapeutic applications, J. Microsc., 218, 133, 10.1111/j.1365-2818.2005.01471.x Chang, 2014, Anticancer efficacy of photodynamic therapy with hematoporphyrin-modified, doxorubicin-loaded nanoparticles in liver cancer, J. Photochem. Photobiol. B, 140, 49, 10.1016/j.jphotobiol.2014.07.005 Okamoto, 2005, Chemical aspects of coumarin compounds for the prevention of hepatocellular carcinomas, Curr. Med. Chem. Anti-Cancer Agents, 5, 47, 10.2174/1568011053352622 Zhang, 2014, N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors, Int. J. Nanomed., 9, 2919, 10.2147/IJN.S59799 Zhu, 2014, Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy, Biomaterials, 35, 5965, 10.1016/j.biomaterials.2014.03.088 Kim, 2015, Tumor-targeted delivery of paclitaxel using low density lipoprotein-Mimetic solid lipid nanoparticles, Mol. Pharm., 12, 1230, 10.1021/mp500737y Michaelis, 2006, Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain, J. Pharmacol. Exp. Ther., 317, 1246, 10.1124/jpet.105.097139 Nikanjam, 2007, Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme, J. Control. Release, 124, 163, 10.1016/j.jconrel.2007.09.007 Liao, 2005, Pleiotropic effects of statins, Annu. Rev. Pharmacool. Toxicol., 45, 89, 10.1146/annurev.pharmtox.45.120403.095748 Pinzón‐Daza, 2014, The association of statins plus LDL receptorótargeted liposomeóencapsulated doxorubicin increases in vitro drug delivery across blood?brain barrier cells, Br. J. Pharmacol., 167, 1431, 10.1111/j.1476-5381.2012.02103.x Kreuter, 2001, Nanoparticulate systems for brain delivery of drugs, Adv. Drug Deliv. Rev., 47, 65, 10.1016/S0169-409X(00)00122-8 Kreuter, 2002, Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier, J. Drug Target., 10, 317, 10.1080/10611860290031877 Friese, 2000, Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly (butylcyanoacrylate) nanoparticles as a parenteral controlled release system, Eur. J. Pharm. Biopharm., 49, 103, 10.1016/S0939-6411(99)00073-9 Zhang, 2013, LDLR-mediated peptide-22-conjugated nanoparticles for dual-targeting therapy of brain glioma, Biomaterials, 34, 9171, 10.1016/j.biomaterials.2013.08.039 Shrivastava, 2014, Low density lipid nanoparticles for solid tumor targeting, Sci. Pharm., 82, 10.3797/scipharm.1401-10 Reynolds, 2014, Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells, Nanomedicine, 9, 2123, 10.2217/nnm.13.187 Zheng, 2002, Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer, Bioconjugate Chem., 13, 392, 10.1021/bc025516h Chu, 2013, Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/amphiphilic materials, ACS Appl. Mater. Interfaces, 5, 7509, 10.1021/am401808e Barczyk, 2010, Integrins, Cell Tissue Res., 339, 269, 10.1007/s00441-009-0834-6 Ramage, 2012, Integrins and extracellular matrix in mechanotransduction, Cell Health Cytoskel., 4, 1 Rathinam, 2010, Important role of integrins in the cancer biology, Cancer Metastasis Rev., 29, 223, 10.1007/s10555-010-9211-x Desgrosellier, 2010, Integrins in cancer: biological implications and therapeutic opportunities, Nat. Rev. Cancer, 10, 9, 10.1038/nrc2748 Humphries, 2006, Integrin ligands at a glance, J. Cell Sci., 119, 3901, 10.1242/jcs.03098 Koivunen, 1995, Phage libraries displaying cyclic peptides with different ring sizes: ligand specificities of the RGD-directed integrins, Nat. Biotechnol., 13, 265, 10.1038/nbt0395-265 Guan, 2008, Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of αvβ6-positive cancers, Bioconjugate Chem., 19, 1813, 10.1021/bc800154f Wang, 2014, RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer, J. Control. Release, 196, 222, 10.1016/j.jconrel.2014.10.012 Ji, 2012, RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy, Cancer. Biol. Ther., 13, 206, 10.4161/cbt.13.4.18692 Dubey, 2011, RGD modified albumin nanospheres for tumour vasculature targeting, J. Pharm. Pharmacol., 63, 33, 10.1111/j.2042-7158.2010.01180.x Temming, 2006, Evaluation of RGD-targeted albumin carriers for specific delivery of auristatin E to tumor blood vessels, Bioconjugate Chem., 17, 1385, 10.1021/bc060087z Xiao, 2012, Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging, Biomaterials, 33, 3071, 10.1016/j.biomaterials.2011.12.030 Miura, 2013, Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood?brain tumor barrier, ACS Nano, 7, 8583, 10.1021/nn402662d Zhan, 2010, conjugated poly (ethylene glycol)-co-poly (lactic acid) micelle enhances paclitaxel anti-glioblastoma effect, J. Control. Release, 143, 136, 10.1016/j.jconrel.2009.12.020 Yang, 2011, cRGD-functionalized, DOX-conjugated, and 64 Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging, Biomaterials, 32, 4151, 10.1016/j.biomaterials.2011.02.006 Ding, 2011, Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers, Nanotechnology, 22, 165101, 10.1088/0957-4484/22/16/165101 Eldar-Boock, 2011, Integrin-assisted drug delivery of nano-scaled polymer therapeutics bearing paclitaxel, Biomaterials, 32, 3862, 10.1016/j.biomaterials.2011.01.073 Chen, 2005, Synthesis and biological evaluation of dimeric RGD peptide-paclitaxel conjugate as a model for integrin-targeted drug delivery, J. Med. Chem., 48, 1098, 10.1021/jm049165z Cao, 2008, Enhancement of antitumor properties of TRAIL by targeted delivery to the tumor neovasculature, Mol. Cancer Ther., 7, 851, 10.1158/1535-7163.MCT-07-0533 Bertilaccio, 2008, Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer, Prostate, 68, 1105, 10.1002/pros.20775 Wang, 2008, Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein, Mol. Cancer Ther., 7, 1044, 10.1158/1535-7163.MCT-07-2084 Arosio, 2011, Cyclic RGD functionalized gold nanoparticles for tumor targeting, Bioconjugate Chem., 22, 664, 10.1021/bc100448r Gormley, 2011, Biological evaluation of RGDfK-gold nanorod conjugates for prostate cancer treatment, J. Drug Target., 19, 915, 10.3109/1061186X.2011.623701 Garg, 2009, Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide, Int. J. Pharm., 366, 201, 10.1016/j.ijpharm.2008.09.016 Shroff, 2012, PEGylated liposomal doxorubicin targeted to α5β1-expressing MDA-MB-231 breast cancer cells, Langmuir, 28, 4729, 10.1021/la204466g Pangburn, 2012, Targeted polymersome delivery of siRNA induces cell death of breast cancer cells dependent upon Orai3 protein expression, Langmuir, 28, 12816, 10.1021/la300874z Marelli, 2013, Tumor targeting via integrin ligands, Front. Oncol., 3, 10.3389/fonc.2013.00222 Guthi, 2009, MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells, Mol. Pharm., 7, 32, 10.1021/mp9001393 DiCara, 2007, Structure-function analysis of Arg-Gly-Asp helix motifs in αvβ6 integrin ligands, J. Biol. Chem., 282, 9657, 10.1074/jbc.M610461200 Ragelle, 2015, Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly (ethylene imine) hybrid nanoparticles: a mechanistic insight, J. Control. Release, 211, 1, 10.1016/j.jconrel.2015.05.274 Schiffelers, 2004, Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle, Nucleic Acids Res., 32, e149, 10.1093/nar/gnh140 Wang, 2014, Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer, ACS Nano, 8, 6620, 10.1021/nn501652j Guo, 2014, Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin α vβ 3 clustering, Biomaterials, 35, 6106, 10.1016/j.biomaterials.2014.04.031 Morlieras, 2013, Functionalization of small rigid platforms with cyclic RGD peptides for targeting tumors overexpressing α vβ 3-integrins, Bioconjugate Chem., 24, 1584, 10.1021/bc4002097 Bolley, 2013, Optimized multimodal nanoplatforms for targeting α vβ 3 integrins, Nanoscale, 5, 11478, 10.1039/c3nr03763k Morales-Avila, 2011, Multimeric system of 99mTc-labeled gold nanoparticles conjugated to c [RGDfK (C)] for molecular imaging of tumor α (v) β (3) expression, Bioconjugate Chem., 22, 913, 10.1021/bc100551s Zhang, 2007, Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner, Cancer Res., 67, 1555, 10.1158/0008-5472.CAN-06-1668 Melemenidis, 2015, Molecular magnetic resonance imaging of angiogenesis In vivo using polyvalent cyclic RGD-Iron oxide microparticle conjugates, Theranostics, 5, 515, 10.7150/thno.10319 Vilchis-Juárez, 2014, Molecular targeting radiotherapy with cyclo-RGDFK (C) peptides conjugated to 177Lu-labeled gold nanoparticles in tumor-bearing mice, J. Biomed. Nanotechnol., 10, 393, 10.1166/jbn.2014.1721 Varki, 1994, Selectin ligands, Proc. Natl. Acad. Sci., 91, 7390, 10.1073/pnas.91.16.7390 Hakomori, 1989, Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens, Adv. Cancer Res., 52, 270 Muramatsu, 1993, Carbohydrate signals in metastasis and prognosis of human carcinomas, Glycobiology, 3, 291, 10.1093/glycob/3.4.291 Liu, 2005, Galectins as modulators of tumour progression, Nat. Rev. Cancer, 5, 29, 10.1038/nrc1527 Gupta, 2009, Targeting cells for drug and gene delivery: emerging applications of mannans and mannan binding lectins, J. Sci. Ind. Res., 68, 465 Seymour, 1995, Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier, Eur. J. Cancer, 31, 766, 10.1016/0959-8049(94)00514-6 Smart, 2004, Lectin-mediated drug delivery in the oral cavity, Adv. Drug Deliv. Rev., 56, 481, 10.1016/j.addr.2003.10.016 David, 2010, Carbohydrate-based biomedical copolymers for targeted delivery of anticancer drugs, Isr. J. Chem., 50, 204, 10.1002/ijch.201000021 Lee, 2000, Affinity enhancement by multivalent lectin–carbohydrate interaction, Glycoconj. J., 17, 543, 10.1023/A:1011070425430 Cho, 2007, Therapeutic nanoparticles for drug delivery in cancer, Kor. J. Otorhinolaryngol. Head Neck Surg., 50, 562 Seymour, 2002, Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin, J. Clin. Oncol., 20, 1668, 10.1200/JCO.2002.20.6.1668 D’Souza, 2013, Comparative in silico–in vivo evaluation of ASGP-R ligands for hepatic targeting of curcumin gantrez nanoparticles, AAPS J., 15, 696, 10.1208/s12248-013-9474-6 Guhagarkar, 2010, Polyethylene sebacate–doxorubicin nanoparticles for hepatic targeting, Int. J. Pharm., 401, 113, 10.1016/j.ijpharm.2010.09.012 Sahu, 2015, Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel, Drug Dev. Ind. Pharm., 41, 640, 10.3109/03639045.2014.891130 Jain, 2010, Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug, J. Control. Release, 148, 359, 10.1016/j.jconrel.2010.09.003 Andrade, 2013, Evaluation of glycophenotype in breast cancer by quantum dot-lectin histochemistry, Int. J. Nanomed., 8, 4623 Ocampo-García, 2011, 99m Tc-labelled gold nanoparticles capped with HYNIC-peptide/mannose for sentinel lymph node detection, Nucl. Med. Biol., 38, 1, 10.1016/j.nucmedbio.2010.07.007 Higuchi, 2008, Mannosylated semiconductor quantum dots for the labeling of macrophages, J. Control. Release, 125, 131, 10.1016/j.jconrel.2007.10.007 Li, 2014, Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells, Front. Mater. Sci., 8, 363, 10.1007/s11706-014-0262-8 Pereira, 2014, Galactodendritic phthalocyanine targets carbohydrate-binding proteins enhancing photodynamic therapy, PLoS One, 9, e95529, 10.1371/journal.pone.0095529 Kluza, 2012, Dual-targeting of α vβ 3 and galectin-1 improves the specificity of paramagnetic/fluorescent liposomes to tumor endothelium in vivo, J. Control. Release, 158, 207, 10.1016/j.jconrel.2011.10.032 Ley, 2003, The role of selectins in inflammation and disease, Trends Mol. Med., 9, 263, 10.1016/S1471-4914(03)00071-6 Banquy, 2008, Selectins ligand decorated drug carriers for activated endothelial cell targeting, Bioconjugate Chem., 19, 2030, 10.1021/bc800257m Obaid, 2015, Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles, Photochem. Photobiol. Sci., 14, 737, 10.1039/C4PP00312H He, 2014, Lectin-conjugated Fe2O3@ Au core@ shell nanoparticles as dual mode contrast agents for in vivo detection of tumor, Mol. Pharm., 11, 738, 10.1021/mp400456j Peer, 2004, Tumor-targeted hyaluronan nanoliposomes increase the antitumor activity of liposomal doxorubicin in syngeneic and human xenograft mouse tumor models, Neoplasia (New York NY), 6, 343, 10.1593/neo.03460 Shen, 2015, Coating solid lipid nanoparticles with hyaluronic acid enhances antitumor activity against melanoma stem-like cells, Theranostics, 5, 755, 10.7150/thno.10804 Maiolino, 2015, Biodegradable nanoparticles sequentially decorated with Polyethyleneimine and Hyaluronan for the targeted delivery of docetaxel to airway cancer cells, J. Nanobiotechnology, 13, 29, 10.1186/s12951-015-0088-2 Yang, 2015, MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer, Sci. Rep., 5 Hall, 1995, Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation, Cell, 82, 19, 10.1016/0092-8674(95)90048-9 Murthy, 2007, Nanoparticles in modern medicine: state of the art and future challenges, Int. J. Nanomed., 2, 129 Mansoori, 2010, A comparative study of two folate-conjugated gold nanoparticles for cancer nanotechnology applications, Cancers, 2, 1911, 10.3390/cancers2041911 Bahrami, 2015, Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy, Tumor Biol., 36, 5727, 10.1007/s13277-015-3706-6 Ye, 2014, Cellular uptake and antitumor activity of DOX-hyd-PEG-FA, Nanoparticles Prabaharan, 2009, Thermosensitive micelles based on folate-conjugated poly (N-vinylcaprolactam)-block-Poly (ethylene glycol) for tumor-targeted drug delivery, Macromol. Biosci., 9, 744, 10.1002/mabi.200800366 Gao, 2011, Prevention of metastasis in a 4T1 murine breast cancer model by doxorubicin carried by folate conjugated pH sensitive polymeric micelles, J. Control. Release, 152, 84, 10.1016/j.jconrel.2011.01.021 Syu, 2012, Improved photodynamic cancer treatment by folate-conjugated polymeric micelles in a KB xenografted animal model, Small, 8, 2060, 10.1002/smll.201102695 Zhang, 2014, Preparation, characterization, and in vitro targeted delivery of folate-conjugated 2-methoxyestradiol-loaded bovine serum albumin nanoparticles, J. Nanopart. Res., 16, 1, 10.1007/s11051-014-2390-6 Zhao, 2010, Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles, Int. J. Nanomed., 5, 669 Liang, 2013, Folate-functionalized nanoparticles for controlled ergosta-4, 6, 8 (14), 22-tetraen-3-one delivery, Int. J. Pharm., 441, 1, 10.1016/j.ijpharm.2012.12.018 Su, 2014, Carboxymethyl-β-cyclodextrin conjugated nanoparticles facilitate therapy for folate receptor-positive tumor with the mediation of folic acid, Int. J. Pharm., 474, 202, 10.1016/j.ijpharm.2014.08.026 Shen, 2011, Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres, Pharmacol. Res., 63, 51, 10.1016/j.phrs.2010.10.012 Hao, 2013, Preparation, characterization, and in vivo evaluation of doxorubicin loaded BSA nanoparticles with folic acid modified dextran surface, Int. J. Pharm., 444, 77, 10.1016/j.ijpharm.2013.01.041 Zu, 2009, Optimization of the preparation process of vinblastine sulfate (VBLS)-loaded folateconjugated bovine serum albumin (BSA) nanoparticles for tumor-targeted drug delivery using response surface methodology (RSM), Int. J. Nanomed., 4, 321, 10.2147/IJN.S8501 Martínez, 2014, Targeting tamoxifen to breast cancer xenograft tumours: preclinical efficacy of folate-attached nanoparticles based on alginate-cysteine/disulphide-bond-reduced albumin, Pharm. Res., 31, 1264, 10.1007/s11095-013-1247-5 Yang, 2014, Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo, Int. J. Nanomed., 9, 4231, 10.2147/IJN.S67210 Shakeri-Zadeh, 2010, Cancerous cells targeting and destruction using folate conjugated gold nanoparticles, Dyn. Biochem. Process Biotechnol. Mol. Biol., 4, 06 Lin, 2013, Biomimetic one-pot synthesis of gold nanoclusters/nanoparticles for targeted tumor cellular dual-modality imaging, Nanoscale Res. Lett., 8, 1, 10.1186/1556-276X-8-170 Cheng, 2013, Surface functionalized gold nanoparticles for drug delivery, J. Biomed. Nanotechnol., 9, 1362, 10.1166/jbn.2013.1536 Pandey, 2013, Biogenic gold nanoparticles as fotillas to fire berberine hydrochloride using folic acid as molecular road map, Mater. Sci. Eng.: C, 33, 3716, 10.1016/j.msec.2013.05.007 Prabaharan, 2009, Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery, Biomaterials, 30, 6065, 10.1016/j.biomaterials.2009.07.048 Lu, 2010, Tumor site?specific silencing of NF-κB p65 by targeted hollow gold nanosphere?mediated photothermal transfection, Cancer Res., 70, 3177, 10.1158/0008-5472.CAN-09-3379 Mehdizadeh, 2014, The effects of folate-conjugated gold nanorods in combination with plasmonic photothermal therapy on mouth epidermal carcinoma cells, Lasers Med. Sci., 29, 939, 10.1007/s10103-013-1414-2 Majd, 2013, Targeted fluoromagnetic nanoparticles for imaging of breast cancer mcf-7 cells, Adv. Pharm. Bull., 3, 189 Varshosaz, 2013, Use of magnetic folate-dextran-retinoic acid micelles for dual targeting of doxorubicin in breast cancer, BioMed Res. Int., 2013, 10.1155/2013/680712 Fazilati, 2014, Folate decorated magnetite nanoparticles: synthesis and targeted therapy against ovarian cancer, Cell Biol. Int., 38, 154, 10.1002/cbin.10167 Wang, 2012, Folate-targeting magnetic core–shell nanocarriers for selective drug release and imaging, Int. J. Pharm., 430, 342, 10.1016/j.ijpharm.2012.04.009 Carpenter, 1979, Epidermal growth factor, Annu. Rev. Biochem, 48, 193, 10.1146/annurev.bi.48.070179.001205 Wieduwilt, 2008, The epidermal growth factor receptor family: biology driving targeted therapeutics, Cell. Mol. Life Sci., 65, 1566, 10.1007/s00018-008-7440-8 Thompson, 1984, receptor: structure, regulation and potential role in malignancy, Cancer Surv., 4, 767 Acharya, 2009, Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy, Biomaterials, 30, 5737, 10.1016/j.biomaterials.2009.07.008 Scaltriti, 2006, The epidermal growth factor receptor pathway: a model for targeted therapy, Clin. Cancer Res., 12, 5268, 10.1158/1078-0432.CCR-05-1554 Nicholson, 2001, EGFR and cancer prognosis, Eur. J. Cancer, 37, 9, 10.1016/S0959-8049(01)00231-3 Ursini-Siegel, 2007, Insights from transgenic mouse models of ERBB2-induced breast cancer, Nat. Rev. Cancer, 7, 389, 10.1038/nrc2127 Lurje, 2009, EGFR signaling and drug discovery, Oncology, 77, 400, 10.1159/000279388 Mendelsohn, 2001, The epidermal growth factor receptor as a target for cancer therapy, Endocr. Relat. Cancer, 8, 3, 10.1677/erc.0.0080003 Gridelli, 2010, Erlotinib in the treatment of non-small cell lung cancer: current status and future developments, Anticancer Res., 30, 1301 Tseng, 2008, Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer, Biomaterials, 29, 3014, 10.1016/j.biomaterials.2008.03.033 Tseng, 2007, Development of gelatin nanoparticles with biotinylated EGF conjugation for lung cancer targeting, Biomaterials, 28, 3996, 10.1016/j.biomaterials.2007.05.006 Shimada, 2009, Development of targeted therapy with paclitaxel incorporated into EGF-conjugated nanoparticles, Anticancer Res., 29, 1009 Tam, 2011 Yuan, 2010, Dendrimer-triglycine-EGF nanoparticles for tumor imaging and targeted nucleic acid and drug delivery, Oral Oncol., 46, 698, 10.1016/j.oraloncology.2010.07.001 Li, 2015, EGF-coated nano-dendriplexes for tumor-targeted nucleic acid delivery in vivo, Drug Deliv., 2015, 1 Sandoval, 2012, EGFR-targeted stearoyl gemcitabine nanoparticles show enhanced anti-tumor activity, J. Control. Release, 157, 287, 10.1016/j.jconrel.2011.08.015 Nikolaev, 2013, Magnetic epidermal growth factor conjugate for targeted delivery to grafted tumor in mouse model, IEEE Trans. Magnet., 49, 429, 10.1109/TMAG.2012.2223203 Shevtsov, 2014, Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors, Int. J. Nanomed., 9, 273, 10.2147/IJN.S55118 Han, 2013, A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro, Int. J. Nanomed., 8, 1541 Kim, 2012, Nanoparticle delivery of a peptide targeting EGFR signaling, J. Control. Release, 157, 279, 10.1016/j.jconrel.2011.08.014 Xu, 2012, Therapeutic gene delivery and transfection in human pancreatic cancer cells using epidermal growth factor receptor-targeted gelatin nanoparticles, J. Visual. Exp.: JoVE, 10.3791/3612 Song, 2009, Novel peptide ligand directs liposomes toward EGF-R high-expressing cancer cells in vitro and in vivo, FASEB J., 23, 1396, 10.1096/fj.08-117002 Chen G-CL, T-S. Jaw, Y-T. Kuo, C-Y. Chen, Y-M. Wang, Targeted new peptide based nanoparticles toward high EGFR expressing cancer cells for MRI 2010. Klutz, 2011, Epidermal growth factor receptor-targeted 131I-therapy of liver cancer following systemic delivery of the sodium iodide symporter gene, Mol. Ther., 19, 676, 10.1038/mt.2010.296 Ren, 2014, EGFR-targeted poly (ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization and in vitro evaluation, Drug Deliv., 1 Master, 2012, EGFR-mediated intracellular delivery of Pc 4 nanoformulation for targeted photodynamic therapy of cancer: in vitro studies, Nanomed.: Nanotechnol. Biol. Med., 8, 655, 10.1016/j.nano.2011.09.012 Chariou, 2015, Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle, Bioconjugate Chem., 26, 262, 10.1021/bc500545z Magadala, 2008, Epidermal growth factor receptor-targeted gelatin-based engineered nanocarriers for DNA delivery and transfection in human pancreatic cancer cells, AAPS J., 10, 565, 10.1208/s12248-008-9065-0 Keefe, 2010, Aptamers as therapeutics, Nat. Rev. Drug Discov., 9, 537, 10.1038/nrd3141 Li, 2010, Directed evolution of gold nanoparticle delivery to cells, Chem. Commun., 46, 392, 10.1039/B920865H Kazemi, 2016, Immunotherapeutic approaches for cancer therapy: an updated review, Artif. Cells Nanomed. Biotechnol., 44, 769 Jadidi-Niaragh, 2016, Downregulation of CD73 in 4T1 breast cancer cells through siRNA-loaded chitosan-lactate nanoparticles, Tumor Biol., 37, 8403, 10.1007/s13277-015-4732-0 Frasco, 2014, Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells, J. Biomed. Mater. Res. A Wang, 2015, Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer, Int. J. Nanomed., 10, 4479, 10.2147/IJN.S84930 Xia, 2013, Activatable cell penetrating peptide-conjugated nanoparticles with enhanced permeability for site-specific targeting delivery of anticancer drug, Bioconjugate Chem., 24, 419, 10.1021/bc300520t Yang, 2012, Skin-permeable quaternary nanoparticles with layer-by-layer structure enabling improved gene delivery, J. Mater. Chem., 22, 10029, 10.1039/c2jm00121g Tseng, 2002, Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study, Mol. Pharmacol., 62, 864, 10.1124/mol.62.4.864 Xia, 2012, Penetratin-functionalized PEG?PLA nanoparticles for brain drug delivery, Int. J. Pharm., 436, 840, 10.1016/j.ijpharm.2012.07.029 Goldammer, 2013 El-Andaloussi, 2005, TP10, a delivery vector for decoy oligonucleotides targeting the Myc protein, J. Control. Release, 110, 189, 10.1016/j.jconrel.2005.09.012 Lehto, 2011, A peptide-based vector for efficient gene transfer in vitro and in vivo, Mol. Ther., 19, 1457, 10.1038/mt.2011.10 MacKay, 2009, Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection, Nat. Mater., 8, 993, 10.1038/nmat2569 McDaniel, 2012, Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild hyperthermia, J. Control. Release, 159, 362, 10.1016/j.jconrel.2012.02.030 Myrberg, 2007, Design of a tumor-homing cell-penetrating peptide, Bioconjugate Chem., 19, 70, 10.1021/bc0701139 Oehlke, 2004, Enhancement of intracellular concentration and biological activity of PNA after conjugation with a cell-penetrating synthetic model peptide, Eur. J. Biochem., 271, 3043, 10.1111/j.1432-1033.2004.04236.x Gao, 2015, Tumor homing cell penetrating peptide decorated nanoparticles used for enhancing tumor targeting delivery and therapy, Int. J. Pharm., 478, 240, 10.1016/j.ijpharm.2014.11.029 Lewin, 2000, Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells, Nat. Biotechnol., 18, 410, 10.1038/74464 Dodd, 2001, Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles, J. Immunol. Methods, 256, 89, 10.1016/S0022-1759(01)00433-1 Goswami, 2015, Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery, Pept. Sci., 104, 712, 10.1002/bip.22672 Tiwari, 2014, Enhanced intracellular translocation and biodistribution of gold nanoparticles functionalized with a cell-penetrating peptide (VG-21) from vesicular stomatitis virus, Biomaterials, 35, 9484, 10.1016/j.biomaterials.2014.07.032 Suk, 2006, Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles, Biomaterials, 27, 5143, 10.1016/j.biomaterials.2006.05.013 Juliano, 2006, Intracellular delivery of oligonucleotide conjugates and dendrimer complexes, Ann. N. Y. Acad. Sci., 1082, 18, 10.1196/annals.1348.011 Reynolds, 2012, Nanoparticle based galectin-1 gene silencing, implications in methamphetamine regulation of HIV-1 infection in monocyte derived macrophages, J. Neuroimmune Pharmacol., 7, 673, 10.1007/s11481-012-9379-7 Hami, 2014, Doxorubicin-conjugated PLA-PEG-Folate based polymeric micelle for tumor-targeted delivery: synthesis and in vitro evaluation, DARU J. Pharm. Sci., 22, 30, 10.1186/2008-2231-22-30 Wu, 2014, Dual-sensitive and folate-conjugated mixed polymeric micelles for controlled and targeted drug delivery, React. Funct. Polym., 81, 82, 10.1016/j.reactfunctpolym.2014.05.003 Guo, 2013, pH-triggered intracellular release from actively targeting polymer micelles, Biomaterials, 34, 4544, 10.1016/j.biomaterials.2013.02.071 Kim, 2008, Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH, Small, 4, 2043, 10.1002/smll.200701275