Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology

Strebhardt, 2008, Paul Ehrlich's magical bullet concept: 100years of progress, Nat. Rev. Cancer, 8, 473, 10.1038/nrc2394 Davis, 2010, Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles, Nature (London), 464, 1067, 10.1038/nature08956 Tabernero, 2013, First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement, Cancer Discov., 3, 406, 10.1158/2159-8290.CD-12-0429 Hrkach, 2012, Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile, Sci. Transl. Med., 4, 128, 10.1126/scitranslmed.3003651 Scheinberg, 2010, Conscripts of the infinite armada: systemic cancer therapy using nanomaterials, Nat. Rev. Clin. Oncol., 7, 266, 10.1038/nrclinonc.2010.38 Peer, 2007, Nanocarriers as an emerging platform for cancer therapy, Nat. Nanotechnol., 2, 751, 10.1038/nnano.2007.387 Kim, 2010, Nanomedicine, New. Engl. J. Med., 363, 2434, 10.1056/NEJMra0912273 Kipp, 2004, The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs, Int. J. Pharm., 284, 109, 10.1016/j.ijpharm.2004.07.019 Zhang, 2008, Self-assembled lipid–polymer hybrid nanoparticles: a robust drug delivery platform, ACS Nano, 2, 1696, 10.1021/nn800275r Whitehead, 2009, Knocking down barriers: advances in siRNA delivery, Nat. Rev. Drug Discov., 8, 129, 10.1038/nrd2742 Alexis, 2008, Factors affecting the clearance and biodistribution of polymeric nanoparticles, Mol. Pharm., 5, 505, 10.1021/mp800051m 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 O'Brien, 2004, Reduced cardiotoxicity and comparable efficacy in a phase III trial of PEGylated liposomal doxorubicin HCl (CAELYX™/Doxil(R)) versus conventional doxorubicin for first-line treatment of metastatic breast cancer, Ann. Oncol., 15, 440, 10.1093/annonc/mdh097 Geisberg, 2010, Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage, Curr. Hypertens. Rep., 12, 404, 10.1007/s11906-010-0146-y Cortes, 2010, Nanoparticle albumin-bound (nab™)-paclitaxel: improving efficacy and tolerability by targeted drug delivery in metastatic breast cancer, Eur. J. Cancer, 8, 1, 10.1016/S1359-6349(10)70002-1 van 't Veer, 2008, Enabling personalized cancer medicine through analysis of gene-expression patterns, Nature, 452, 564, 10.1038/nature06915 Basu, 2009, Targeting oncogenic signaling pathways by exploiting nanotechnology, Cell Cycle, 8, 3480, 10.4161/cc.8.21.9851 Baselga, 2006, Targeting tyrosine kinases in cancer: the second wave, Science, 312, 1175, 10.1126/science.1125951 Martini, 2012, Targeted therapies: how personal should we go?, Nat. Rev. Clin. Oncol., 9, 87, 10.1038/nrclinonc.2011.164 Zhang, 2009, Targeting cancer with small molecule kinase inhibitors, Nat. Rev. Cancer, 9, 28, 10.1038/nrc2559 Valencia, 2012, Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles, Nanomedicine, 8, 687, 10.2217/nnm.12.134 Xu, 2013, Enhancing tumor cell response to chemotherapy through nanoparticle-mediated co-delivery of siRNA and cisplatin prodrug, Proc. Natl. Acad. Sci. U S A, 110, 18638, 10.1073/pnas.1303958110 Yu, 2002, Effect of p53 status on tumor response to antiangiogenic therapy, Science, 295, 1526, 10.1126/science.1068327 Sun, 2012, Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B, Nat. Med., 18, 1359, 10.1038/nm.2890 Sengupta, 2005, Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system, Nature, 436, 568, 10.1038/nature03794 Tuma, 2013, Pancreatic cancer: gemcitabine plus nab-paclitaxel prolongs survival in patients with metastatic disease, Oncol. Times, 35, 6, 10.1097/01.COT.0000427826.53087.1a Prabhakar, 2013, Challenges and key considerations of the enhanced permeability and retention effect (EPR) for nanomedicine drug delivery in oncology, Cancer Res., 73, 2412, 10.1158/0008-5472.CAN-12-4561 Carmeliet, 2011, Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases, Nat. Rev. Drug Discov., 10, 417, 10.1038/nrd3455 Leserman, 1980, Receptor-mediated endocytosis of antibody-opsonized liposomes by tumor cells, Proc. Natl. Acad. Sci., 77, 4089, 10.1073/pnas.77.7.4089 Leserman, 1980, Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein, Nature, 288, 602, 10.1038/288602a0 Heath, 1980, Antibody targeting of liposomes: cell specificity obtained by conjugation of F(ab′)2 to vesicle, surface, Science, 210, 539, 10.1126/science.7423203 Warenius, 1981, Attempted targeting of a monoclonal-antibody in a human-tumor xenograft system, Eur. J. Cancer Clin. Oncol., 17, 1009, 10.1016/S0277-5379(81)80006-5 Kamaly, 2012, Targeted polymeric therapeutic nanoparticles: design, development and clinical translation, Chem. Soc. Rev., 41, 2971, 10.1039/c2cs15344k Idris, 2012, In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers, Nat. Med., 18, 1580, 10.1038/nm.2933 Huang, 2010, Remote control of ion channels and neurons through magnetic-field heating of nanoparticles, Nat. Nanotechnol., 5, 602, 10.1038/nnano.2010.125 Cho, 2012, A magnetic switch for the control of cell death signalling in in vitro and in vivo systems, Nat. Mater., 11, 1038, 10.1038/nmat3430 Burke, 2012, Markedly enhanced skeletal muscle transfection achieved by the ultrasound-targeted delivery of non-viral gene nanocarriers with microbubbles, J. Control. Release, 162, 414, 10.1016/j.jconrel.2012.07.005 Burke, 2011, Inhibition of glioma growth by microbubble activation in a subcutaneous model using low duty cycle ultrasound without significant heating, J. Neurosurg., 114, 1654, 10.3171/2010.11.JNS101201 Matsumura, 1986, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res., 46, 6387 Maeda, 2001, SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy, Adv. Drug Deliv. Rev., 46, 169, 10.1016/S0169-409X(00)00134-4 Kobayashi, 1988, Protein binding of macromolecular anticancer agent SMANCS: characterization of poly(styrene-co-maleic acid) derivatives as an albumin binding ligand, J. Bioact. Compat. Polym., 3, 319, 10.1177/088391158800300401 Bates, 2002, Regulation of microvascular permeability by vascular endothelial growth factors*, J. Anat., 200, 581, 10.1046/j.1469-7580.2002.00066.x Jain, 1998, The next frontier of molecular medicine: delivery of therapeutics, Nat. Med., 4, 655, 10.1038/nm0698-655 Jain, 2010, Delivering nanomedicine to solid tumors, Nat. Rev. Clin. Oncol., 7, 653, 10.1038/nrclinonc.2010.139 Hobbs, 1998, Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment, Proc. Natl. Acad. Sci. U. S. A., 95, 4607, 10.1073/pnas.95.8.4607 Swartz, 2007, Interstitial flow and its effects in soft tissues, Annu. Rev. Biomed. Eng., 9, 229, 10.1146/annurev.bioeng.9.060906.151850 Padera, 2004, Pathology: cancer cells compress intratumour vessels, Nature, 427, 695, 10.1038/427695a Jain, 1987, Transport of molecules across tumor vasculature, Cancer Metastsis Rev., 6, 559, 10.1007/BF00047468 Swartz, 2001, The physiology of the lymphatic system, Adv. Drug Deliv. Rev., 50, 3, 10.1016/S0169-409X(01)00150-8 Noguchi, 1998, Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues, Jpn. J. Cancer Res., 89, 307, 10.1111/j.1349-7006.1998.tb00563.x Rabanel, 2012, Drug-loaded nanocarriers: passive targeting and crossing of biological barriers, Curr. Med. Chem., 19, 3070, 10.2174/092986712800784702 Stacker, 2002, Metastasis: lymphangiogenesis and cancer metastasis, Nat. Rev. Cancer, 2, 573, 10.1038/nrc863 Stylianopoulos, 2013, Cationic nanoparticles have superior transvascular flux into solid tumors: insights from a mathematical model, Ann. Biomed. Eng., 41, 68, 10.1007/s10439-012-0630-4 Dellian, 2000, Vascular permeability in a human tumour xenograft: molecular charge dependence, Br. J. Cancer, 82, 1513 Schmitt-Sody, 2003, Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy, Clin. Cancer Res., 9, 2335 Krasnici, 2003, Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels, Int. J. Cancer, 105, 561, 10.1002/ijc.11108 Zamboni, 2011, Tumor disposition of pegylated liposomal CKD-602 and the reticuloendothelial system in preclinical tumor models, J. Liposome Res., 21, 70, 10.3109/08982101003754385 Hashizume, 2000, Openings between defective endothelial cells explain tumor vessel leakiness, Am. J. Pathol., 156, 1363, 10.1016/S0002-9440(10)65006-7 Netti, 1999, Enhancement of fluid filtration across tumor vessels: implication for delivery of macromolecules, Proc. Natl. Acad. Sci. U. S. A., 96, 3137, 10.1073/pnas.96.6.3137 Lieleg, 2009, Selective filtering of particles by the extracellular matrix: an electrostatic bandpass, Biophys. J., 97, 1569, 10.1016/j.bpj.2009.07.009 Alexandrakis, 2004, Two-photon fluorescence correlation microscopy reveals the two-phase nature of transport in tumors, Nat. Med., 10, 203, 10.1038/nm981 Netti, 2000, Role of extracellular matrix assembly in interstitial transport in solid tumors, Cancer Res., 60, 2497 McKee, 2006, Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic Herpes Simplex virus vector, Cancer Res., 66, 2509, 10.1158/0008-5472.CAN-05-2242 Caron, 2012, Interpatient pharmacokinetic and pharmacodynamic variability of carrier-mediated anticancer agents, Clin. Pharmacol. Ther., 91, 802, 10.1038/clpt.2012.12 Zamboni, 2011, Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors, J. Liposome Res., 21, 158, 10.3109/08982104.2010.496085 Sano, 2013, Markedly enhanced permeability and retention effects induced by photo-immunotherapy of tumors, ACS Nano, 7, 717, 10.1021/nn305011p Diop-Frimpong, 2011, Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors, Proc. Natl. Acad. Sci., 108, 2909, 10.1073/pnas.1018892108 Noguchi, 1992, Enhanced tumor localization of monoclonal antibody by treatment with kininase II inhibitor and angiotensin II, Jpn. J. Cancer Res., 83, 240, 10.1111/j.1349-7006.1992.tb00093.x Maeda, 2010, Nitroglycerin enhances vascular blood flow and drug delivery in hypoxic tumor tissues: analogy between angina pectoris and solid tumors and enhancement of the EPR effect, J. Control. Release, 142, 296, 10.1016/j.jconrel.2010.01.002 Maeda, 2012, Macromolecular therapeutics in cancer treatment: the EPR effect and beyond, J. Control. Release, 164, 138, 10.1016/j.jconrel.2012.04.038 Fang, 2012, Carbon monoxide, generated by heme oxygenase-1, mediates the enhanced permeability and retention effect in solid tumors, Cancer Sci., 103, 535, 10.1111/j.1349-7006.2011.02178.x Chauhan, 2012, Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner, Nat. Nanotechnol., 7, 384, 10.1038/nnano.2012.45 Kano, 2009, Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-β receptor inhibitor on extravasation of nanoparticles from neovasculature, Cancer Sci., 100, 173, 10.1111/j.1349-7006.2008.01003.x Cabral, 2011, Accumulation of sub-100nm polymeric micelles in poorly permeable tumours depends on size, Nat. Nanotechnol., 6, 815, 10.1038/nnano.2011.166 Kano, 2007, Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-β signaling, Proc. Natl. Acad. Sci. U. S. A., 104, 3460, 10.1073/pnas.0611660104 Maeda, 2001, The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting, Adv. Enzyme Regul., 41, 189, 10.1016/S0065-2571(00)00013-3 Dreher, 2006, Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers, JNCI, J. Natl. Cancer Inst., 98, 335, 10.1093/jnci/djj070 Murakami, 1997, Tumor accumulation of poly(ethylene glycol) with different molecular weights after intravenous injection, Drug Deliv., 4, 23, 10.3109/10717549709033184 Fox, 2009, Soluble polymer carriers for the treatment of cancer: the importance of the molecular architecture, Acc. Chem. Res., 42, 1141, 10.1021/ar900035f Allen, 1995, Pharmacokinetics and anti-tumor activity of vincristine encapsulated in sterically stabilized liposomes, Int. J. Cancer, 62, 199, 10.1002/ijc.2910620215 Torchilin, 2005, Recent advances with liposomes as pharmaceutical carriers, Nat. Rev. Drug Discov., 4, 145, 10.1038/nrd1632 Perrault, 2009, Mediating tumor targeting efficiency of nanoparticles through design, Nano Lett., 9, 1909, 10.1021/nl900031y Huo, 2013, Superior penetration and retention behavior of 50nm gold nanoparticles in tumors, Cancer Res., 73, 319, 10.1158/0008-5472.CAN-12-2071 Wong, 2011, Multistage nanoparticle delivery system for deep penetration into tumor tissue, Proc. Natl. Acad. Sci. U. S. A., 108, 2426, 10.1073/pnas.1018382108 Takakura, 1998, Extravasation of macromolecules, Adv. Drug Deliv. Rev., 34, 93, 10.1016/S0169-409X(98)00006-4 Scherphof, 2001, The role of hepatocytes in the clearance of liposomes from the blood circulation, Prog. Lipid Res., 40, 149, 10.1016/S0163-7827(00)00020-5 Nishida, 1991, Hepatic disposition characteristics of electrically charged macromolecules in rat in vivo and in the perfused liver, Pharm. Res., 8, 437, 10.1023/A:1015886708598 Salvador-Morales, 2009, Immunocompatibility properties of lipid–polymer hybrid nanoparticles with heterogenous surface functional groups, Biomaterials, 30, 2231, 10.1016/j.biomaterials.2009.01.005 Chonn, 1991, The role of surface charge in the activation of the classical and alternative pathways of complement by liposomes, J. Immunol., 146, 4234, 10.4049/jimmunol.146.12.4234 He, 2010, Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles, Biomaterials, 31, 3657, 10.1016/j.biomaterials.2010.01.065 Xiao, 2011, The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles, Biomaterials, 32, 3435, 10.1016/j.biomaterials.2011.01.021 Levchenko, 2002, Liposome clearance in mice: the effect of a separate and combined presence of surface charge and polymer coating, Int. J. Pharm., 240, 95, 10.1016/S0378-5173(02)00129-1 Arvizo, 2011, Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles, PLoS ONE, 6, e24374, 10.1371/journal.pone.0024374 Gabizon, 1988, Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors, Proc. Natl. Acad. Sci. U. S. A., 85, 6949, 10.1073/pnas.85.18.6949 Roux, 2003, On the characterization of pH-sensitive liposome/polymer complexes, Biomacromolecules, 4, 240, 10.1021/bm025651x Peer, 2004, Tumor-targeted hyaluronan nanoliposomes increase the antitumor activity of liposomal doxorubicin in syngeneic and human xenograft mous tumor models, Neoplasia, 6, 343, 10.1593/neo.03460 Yamamoto, 2001, Long-circulating poly(ethylene glycol)-poly(d, l-lactide) block copolymer micelles with modulated surface charge, J. Control. Release, 77, 27, 10.1016/S0168-3659(01)00451-5 Campbell, 2002, Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors, Cancer Res., 62, 6831 Strieth, 2008, Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with cisplatin, Clin. Cancer Res., 14, 4603, 10.1158/1078-0432.CCR-07-4738 Löhr, 2012, Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial, Ann. Oncol., 23, 1214, 10.1093/annonc/mdr379 Fasol, 2012, Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis, Ann. Oncol., 23, 1030, 10.1093/annonc/mdr300 Meng, 2011, Use of size and a copolymer design feature to improve the biodistribution and the enhanced permeability and retention effect of doxorubicin-loaded mesoporous silica nanoparticles in a murine xenograft tumor model, ACS Nano, 5, 4131, 10.1021/nn200809t Ho, 2010, Characterization of cationic liposome formulations designed to exhibit extended plasma residence times and tumor vasculature targeting properties, J. Pharm. Sci., 99, 2839, 10.1002/jps.22043 Han, 2013, Spatial charge configuration regulates nanoparticle transport and binding behavior in vivo, Angew. Chem. Int. Ed., 52, 1414, 10.1002/anie.201208331 Nomura, 1998, Effect of particle size and charge on the disposition of lipid carriers after intratumoral injection into tissue-isolated tumors, Pharm. Res., 15, 128, 10.1023/A:1011921324952 Nomura, 1998, Pharmacokinetic characteristics and therapeutic effects of mitomycin C-dextran conjugates after intratumoural injection, J. Control. Release, 52, 239, 10.1016/S0168-3659(97)00185-5 Champion, 2009, Shape induced inhibition of phagocytosis of polymer particles, Pharm. Res., 26, 244, 10.1007/s11095-008-9626-z Champion, 2006, Role of target geometry in phagocytosis, Proc. Natl. Acad. Sci. U. S. A., 103, 4930, 10.1073/pnas.0600997103 Geng, 2007, Shape effects of filaments versus spherical particles in flow and drug delivery, Nat. Nanotechnol., 2, 249, 10.1038/nnano.2007.70 Ruggiero, 2010, Paradoxical glomerular filtration of carbon nanotubes, Proc. Natl. Acad. Sci. U. S. A., 107, 12369, 10.1073/pnas.0913667107 Chauhan, 2011, Fluorescent nanorods and nanospheres for real-time in vivo probing of nanoparticle shape-dependent tumor penetration, Angew. Chem. Int. Ed., 50, 11417, 10.1002/anie.201104449 Shukla, 2013, Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle potato virus X, Mol. Pharm., 10, 33, 10.1021/mp300240m Lammers, 2012, Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress, J. Control. Release, 161, 175, 10.1016/j.jconrel.2011.09.063 Taurin, 2012, Anticancer nanomedicine and tumor vascular permeability; where is the missing link?, J. Control. Release, 164, 265, 10.1016/j.jconrel.2012.07.013 Liu, 2012, Biodistribution studies of nanoparticles using fluorescence imaging: a qualitative or quantitative method?, Pharm. Res., 29, 3273, 10.1007/s11095-012-0818-1 Gabizon, 1994, Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes, Cancer Res., 54, 987 Northfelt, 1996, Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma, J. Clin. Pharmacol., 36, 55, 10.1002/j.1552-4604.1996.tb04152.x Symon, 1999, Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes, Cancer, 86, 72, 10.1002/(SICI)1097-0142(19990701)86:1<72::AID-CNCR12>3.0.CO;2-1 Harrington, 2001, Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled PEGylated liposomes, Clin. Cancer Res., 7, 243 Koukourakis, 2000, High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas: rationale for combination with radiotherapy, Acta Oncol., 39, 207, 10.1080/028418600430789 Koukourakis, 2000, High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx(r)) in glioblastomas and in metastatic brain tumours, Br. J. Cancer, 83, 1281, 10.1054/bjoc.2000.1459 Han, 2006, In vivo distribution and antitumor activity of heparin-stabilized doxorubicin-loaded liposomes, Int. J. Pharm., 313, 181, 10.1016/j.ijpharm.2006.02.007 Harrington, 2001, The effect of irradiation on the biodistribution of radiolabeled pegylated liposomes, Int. J. Radiat. Oncol. Biol. Phys., 50, 809, 10.1016/S0360-3016(01)01508-5 La-Beck, 2012, Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients, Cancer Chemother. Pharmacol., 69, 43, 10.1007/s00280-011-1664-2 Schroeder, 2012, Treating metastatic cancer with nanotechnology, Nat. Rev. Cancer, 12, 39, 10.1038/nrc3180 Gabizon, 2003, Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies, Clin. Pharmacokinet., 42, 419, 10.2165/00003088-200342050-00002 Caron, 2011, Allometric scaling of pegylated liposomal anticancer drugs, J. Pharmacokinet. Pharmacodyn., 38, 653, 10.1007/s10928-011-9213-5 Zamboni, 2012, Best practices in cancer nanotechnology: perspective from NCI nanotechnology alliance, Clin. Cancer Res., 18, 3229, 10.1158/1078-0432.CCR-11-2938 Kummar, 2008, Phase 0 clinical trials: conceptions and misconceptions, Cancer J., 14, 133, 10.1097/PPO.0b013e318172d6f3 Karathanasis, 2009, Imaging nanoprobe for prediction of outcome of nanoparticle chemotherapy by using mammography, Radiology, 250, 398, 10.1148/radiol.2502080801 Daldrup-Link, 2011, MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles, Clin. Cancer Res., 17, 5695, 10.1158/1078-0432.CCR-10-3420 Harisinghani, 2003, Noninvasive detection of clinically occult lymph-node metastases in prostate cancer, N. Engl. J. Med., 348, 2491, 10.1056/NEJMoa022749 Gaglia, 2011, Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients, J. Clin. Invest., 121, 442, 10.1172/JCI44339 Zhang, 2012, Interactions of nanomaterials and biological systems: implications to personalized nanomedicine, Adv. Drug Deliv. Rev., 64, 1363, 10.1016/j.addr.2012.08.005 Karnik, 2008, Microfluidic platform for controlled synthesis of polymeric nanoparticles, Nano Lett., 8, 2906, 10.1021/nl801736q Kolishetti, 2010, Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy, Proc Natl Acad Sci U S A, 107, 17939-1744, 10.1073/pnas.1011368107 Aryal, 2010, Combinatorial drug conjugation enables nanoparticle dual-drug delivery, Small, 6, 1442, 10.1002/smll.201000631 Bertrand, 2009, Pharmacokinetics and biodistribution of N-isopropylacrylamide copolymers for the design of pH-sensitive liposomes, Biomaterials, 30, 2598, 10.1016/j.biomaterials.2008.12.082 Gao, 2010, Poly(ethylene glycol) with observable shedding, Angew. Chem. Int. Ed., 49, 6567, 10.1002/anie.201001868 Bissery, 1995, Docetaxel (Taxotere(R)) a review of preclinical and clinical experience, Part I: preclinical experience, Anti-Cancer Drugs, 6, 339, 10.1097/00001813-199506000-00001 Ullal, 2011, Nanoparticle-Mediated measurement of target–drug binding in cancer cells, ACS Nano, 5, 9216, 10.1021/nn203450p Shi, 2011, Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation, Acc. Chem. Res., 44, 1123, 10.1021/ar200054n Cheng, 2012, Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities, Science, 338, 903, 10.1126/science.1226338 Koshkaryev, 2013, Immunoconjugates and long circulating systems: origins, current state of the art and future directions, Adv. Drug Deliv. Rev., 65, 24, 10.1016/j.addr.2012.08.009 Byrne, 2008, Active targeting schemes for nanoparticle systems in cancer therapeutics, Adv. Drug Deliv. Rev., 60, 1615, 10.1016/j.addr.2008.08.005 Alexis, 2008, Factors affecting the clearance and biodistribution of polymeric nanoparticles, Mol. Pharm., 5, 505, 10.1021/mp800051m Monopoli, 2012, Biomolecular coronas provide the biological identity of nanosized materials, Nat. Nanotechnol., 7, 779, 10.1038/nnano.2012.207 Gu, 2008, Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers, Proc. Natl. Acad. Sci. U. S. A., 105, 2586, 10.1073/pnas.0711714105 Jiang, 2008, Nanoparticle-mediated cellular response is size-dependent, Nat. Nanotechnol., 3, 145, 10.1038/nnano.2008.30 Valencia, 2011, Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles, Biomaterials, 32, 6226, 10.1016/j.biomaterials.2011.04.078 Saha, 2010, Nanoparticulate drug delivery systems for cancer chemotherapy, Mol. Membr. Biol., 27, 215, 10.3109/09687688.2010.510804 Yu, 2010, Receptor-targeted nanocarriers for therapeutic delivery to cancer, Mol. Membr. Biol., 27, 286, 10.3109/09687688.2010.521200 Rieux, 2013, Targeted nanoparticles with novel non-peptidic ligands for oral delivery, Adv. Drug Deliv. Rev., 65, 833, 10.1016/j.addr.2013.01.002 Wang, 2010, The complex role fo multivalency in nanoparticles targeting the transferrin receptor for cancer therapies, J. Am. Chem. Soc., 132, 11306, 10.1021/ja1043177 Wu, 2013, Water insoluble cationic poly(ester amide)s: synthesis, characterization and applications, J. Math. Chem. B, 1, 353, 10.1039/C2TB00070A Florence, 2012, “Targeting” nanoparticles: the constraints of physical laws and physical barriers, J. Control. Release, 164, 115, 10.1016/j.jconrel.2012.03.022 Pirollo, 2008, Does a targeting ligand influence nanoparticle tumor localization or uptake?, Trends Biotechnol., 26, 552, 10.1016/j.tibtech.2008.06.007 Kirpotin, 2006, Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models, Cancer Res., 66, 6732, 10.1158/0008-5472.CAN-05-4199 Bartlett, 2007, Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging, Proc. Natl. Acad. Sci. U. S. A., 104, 15549, 10.1073/pnas.0707461104 Farokhzad, 2009, Impact of nanotechnology on drug delivery, ACS Nano, 3, 16, 10.1021/nn900002m Farokhzad, 2006, Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo, Proc. Natl. Acad. Sci. U. S. A., 103, 6315, 10.1073/pnas.0601755103 Sahay, 2010, Endocytosis of nanomedicines, J. Control. Release, 145, 182, 10.1016/j.jconrel.2010.01.036 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 Bareford, 2007, Endocytic mechanisms for targeted drug delivery, Adv. Drug Deliv. Rev., 59, 748, 10.1016/j.addr.2007.06.008 Bhattacharyya, 2011, Efficient delivery of gold nanoparticles by dual receptor targeting, Adv. Mater., 23, 5034, 10.1002/adma.201102287 Li, 2011, Enhancement of cell recognition in vitro by dual-ligand cancer targeting gold nanoparticles, Biomaterials, 32, 2540, 10.1016/j.biomaterials.2010.12.031 Papademetriou, 2013, In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors, Biomaterials, 34, 3459, 10.1016/j.biomaterials.2013.01.069 Gao, 2010, Antibody engineering promotes nanomedicine for cancer treatment, Nanomedicine, 5, 1141, 10.2217/nnm.10.94 Duncan, 2005, Polymer–drug conjugates: towards a novel approach for the treatment of endrocine-related cancer, Endocrinol. Relat. Cancer, 12, S189, 10.1677/erc.1.01045 Ghosh, 2008, Gold nanoparticles in delivery applications, Adv. Drug Deliv. Rev., 60, 1307, 10.1016/j.addr.2008.03.016 Zhang, 2011, The application of carbon nanotubes in target drug delivery systems for cancer therapies, Nanoscale Res. Lett., 6, 555, 10.1186/1556-276X-6-555 Liong, 2008, Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery, ACS Nano, 2, 889, 10.1021/nn800072t Veiseh, 2010, Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging, Adv. Drug Deliv. Rev., 62, 284, 10.1016/j.addr.2009.11.002 Wu, 2012, Cationic hybrid hydrogels from amino-acid-based poly(ester amide): fabrication, characterization, and biological properties, Adv. Funct. Mater., 22, 3815, 10.1002/adfm.201103147 Barrera, 1993, Synthesis and RGD peptide modification of a new biodegradable copolymer: poly(lactic acid-co-lysine), J. Am. Chem. Soc., 115, 11010, 10.1021/ja00076a077 Heller, 2002, Poly(ortho esters): synthesis, characterization, properties and uses, Adv. Drug Deliv. Rev., 54, 1015, 10.1016/S0169-409X(02)00055-8 Silvius, 1993, Interbilayer transfer of phospholipid-anchored macromolecules via monomer diffusion, Biochemistry, 32, 3153, 10.1021/bi00063a030 Uhrich, 1999, Polymeric systems for controlled drug release, Chem. Rev., 99, 3181, 10.1021/cr940351u Delehanty, 2010, Peptides for specific intracellular delivery and targeting of nanoparticles: implications for developing nanoparticle-mediated drug delivery, Ther. Deliv., 1, 411, 10.4155/tde.10.27 Yu, 2012, Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy, Theranostics, 2, 3, 10.7150/thno.3463 Singh, 1996, Formation of N-substituted 2-iminothiolanes when amino groups in proteins and peptides are modified by 2-iminothiolane, Anal. Biochem., 236, 114, 10.1006/abio.1996.0139 Kumar, 1991, A simple method for introducing a thiol group at the 5′-end of synthetic oligonucleotides, Nucleic Acids Res., 19, 4561, 10.1093/nar/19.16.4561 Shi, 2009, Organic nanoscale drug carriers coupled with ligands for targeted drug delivery in cancer, J. Math. Chem., 19, 5485, 10.1039/b822319j Fischer, 2010, Amine coupling through EDC/NHS: a practical approach, 55 Park, 2011, Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates, J. Control. Release, 156, 109, 10.1016/j.jconrel.2011.06.025 Fahmy, 2005, Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting, Biomaterials, 26, 5727, 10.1016/j.biomaterials.2005.02.025 Yumura, 2013, Mutations for decreasing the immunogenicity and maintaining the function of core streptavidin, Protein Sci., 22, 213, 10.1002/pro.2203 Rao, 1998, A trivalent system from vancomycin·d-Ala-d-Ala with higher affinity than avidin·biotin, Science, 280, 708, 10.1126/science.280.5364.708 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 Bartlett, 2007, Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles, Bioconjug. Chem., 18, 456, 10.1021/bc0603539 Mammen, 1998, Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors, Angew. Chem. Int. Ed., 37, 2754, 10.1002/(SICI)1521-3773(19981102)37:20<2754::AID-ANIE2754>3.0.CO;2-3 Wu, 2008, Carbon nanotubes protect DNA strands during cellular delivery, ACS Nano, 2, 2023, 10.1021/nn800325a Seferos, 2008, Polyvalent DNA nanoparticle conjugates stabilize nucleic acids, Nano Lett., 9, 308, 10.1021/nl802958f Bertrand, 2013, Designing polymeric binders for pharmaceutical applications, 483 Mukherjee, 1997, Endocytosis, Physiol. Rev., 77, 759, 10.1152/physrev.1997.77.3.759 Weissleder, 2005, Cell-specific targeting of nanoparticles by multivalent attachment of small molecules, Nat. Biotechnol., 23, 1418, 10.1038/nbt1159 Stefanick, 2013, A systematic analysis of peptide linker length and liposomal polyethylene glycol coating on cellular uptake of peptide-targeted liposomes, ACS Nano, 7, 2935, 10.1021/nn305663e Elias, 2013, Effect of ligand density, receptor density, and nanoparticle size on cell targeting, Nanomedicine, 9, 194, 10.1016/j.nano.2012.05.015 Poon, 2010, Ligand-clustered “patchy” nanoparticles for modulated cellular uptake and in vivo tumor targeting, Angew. Chem. Int. Ed., 49, 7266, 10.1002/anie.201003445 Allen, 2002, Ligand-targeted therapeutics in anticancer therapy, Nat. Rev. Cancer, 2, 750, 10.1038/nrc903 Fujimori, 1989, Modeling Analysis of the global and microscopic distribution of immunoglobulin G, F(ab′)2, and Fab in tumors, Cancer Res., 49, 5656 Rudnick, 2009, Affinity and avidity in antibody-based tumor targeting, Cancer Biother. Radiopharm., 24, 155, 10.1089/cbr.2009.0627 Thurber, 2011, Quantitating antibody uptake in vivo: conditional dependence on antigen expression levels, Mol. Imaging Biol., 13, 623, 10.1007/s11307-010-0397-7 Fujimori, 1990, A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier, J. Nucl. Med., 31, 1191 van Osdol, 1991, An analysis of monoclonal antibody distribution in microscopic tumor nodules: consequences of a “binding site barrier”, Cancer Res., 51, 4776 Juweid, 1992, Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier, Cancer Res., 52, 5144 Weinstein, 1992, The macroscopic and microscopic pharmacology of monoclonal antibodies, Int. J. Immunopharmacol., 14, 457, 10.1016/0192-0561(92)90176-L Primeau, 2005, The distribution of the anticancer drug doxorubicin in relation to blood vessels in solid tumors, Clin. Cancer Res., 11, 8782, 10.1158/1078-0432.CCR-05-1664 Lee, 2010, The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles, Mol. Pharm., 7, 1195, 10.1021/mp100038h Ghitescu, 1990, Immunolabeling efficiency of protein A-gold complexes, J. Histochem. Cytochem., 38, 1523, 10.1177/38.11.2212613 Gratton, 2008, The effect of particle design on cellular internalization pathways, Proc. Natl. Acad. Sci. U. S. A., 105, 11613, 10.1073/pnas.0801763105 Moradi, 2012, Ligand density and clustering effects on endocytosis of folate modified nanoparticles, RSC Adv., 2, 3025, 10.1039/c2ra01168a Petros, 2010, Strategies in the design of nanoparticles for therapeutic applications, Nat. Rev. Drug Discov., 9, 615, 10.1038/nrd2591 Wang, 2010, The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies, J. Am. Chem. Soc., 132, 11306, 10.1021/ja1043177 Barua, 2013, Particle shape enhances specificity of antibody-displaying nanoparticles, Proc. Natl. Acad. Sci., 110, 3270, 10.1073/pnas.1216893110 Vincent, 2009, Protonated nanoparticle surface governing ligand tethering and cellular targeting, ACS Nano, 3, 1203, 10.1021/nn9000148 Kocbek, 2007, Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody, J. Control. Release, 120, 18, 10.1016/j.jconrel.2007.03.012 Patil, 2009, Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery, Biomaterials, 30, 859, 10.1016/j.biomaterials.2008.09.056 Zhao, 2011, Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials, Small, 7, 1322, 10.1002/smll.201100001 Sun, 2013, Functionalization of quantum dots with multidentate zwitterionic ligands: impact on cellular interactions and cytotoxicity, J. Mater. Chem. B, 1, 6137, 10.1039/c3tb20894j Hongwei, 2013, ‘Living’ PEGylation on gold nanoparticles to optimize cancer cell uptake by controlling targeting ligand and charge densities, Nanotechnology, 24, 355101, 10.1088/0957-4484/24/35/355101 Wu, 2012, Block copolymer of poly(ester amide) and polyesters: synthesis, characterization, and in vitro cellular response, Acta Biomater., 8, 4314, 10.1016/j.actbio.2012.07.027 Salvati, 2013, Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface, Nat. Nanotechnol., 8, 137, 10.1038/nnano.2012.237 Mori, 1991, Influence of the steric barrier activity of amphiphatic poly(ethylene glycol) and ganglioside GM1 on the circulation time of the liposomes and on the target binding of immunoliposomes in vivo, FEBS Lett., 284, 263, 10.1016/0014-5793(91)80699-4 Hak, 2012, The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging, ACS Nano, 6, 5648, 10.1021/nn301630n Gao, 2004, In vivo cancer targeting and imaging with semiconductor quantum dots, Nat. Biotechnol., 22, 969, 10.1038/nbt994 Hamaguchi, 2004, Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts, Cancer Sci., 95, 608, 10.1111/j.1349-7006.2004.tb02495.x Park, 2002, Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery, Clin. Cancer Res., 8, 1172 Winkler, 2009, EpCAM-targeted delivery of nanocomplexed siRNA to tumor cells with designed ankyrin repeat proteins, Mol. Cancer Ther., 8, 2674, 10.1158/1535-7163.MCT-09-0402 Alexis, 2008, HER-2-targeted nanoparticle–affibody bioconjugates for cancer therapy, ChemMedChem, 3, 1839, 10.1002/cmdc.200800122 Karmali, 2009, Targeting of albumin-embedded paclitaxel nanoparticles to tumors, Nanomedicine, 5, 73, 10.1016/j.nano.2008.07.007 Park, 2008, Magnetic iron oxide nanoworms for tumor targeting and imaging, Adv. Mater., 20, 1630, 10.1002/adma.200800004 Sugahara, 2009, Tissue-penetrating delivery of compounds and nanoparticles into tumors, Cancer Cell, 16, 510, 10.1016/j.ccr.2009.10.013 Graf, 2012, αVβ3 Integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug, ACS Nano, 6, 4530, 10.1021/nn301148e Kamaly, 2013, Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles, Proc Natl Acad Sci U S A, 110, 6506, 10.1073/pnas.1303377110 Chan, 2010, Spatiotemporal controlled delivery of nanoparticles to injured vasculature, Proc. Natl. Acad. Sci. U. S. A., 107, 2213, 10.1073/pnas.0914585107 Chan, 2011, In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid-polymeric nanoparticles, Proc. Natl. Acad. Sci., 108, 19347, 10.1073/pnas.1115945108 Saw, 2013, Aptide-conjugated liposome targeting tumor-associated fibronectin for glioma therapy, J. Math. Chem. B, 1, 4723, 10.1039/c3tb20815j Cheng, 2007, Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery, Biomaterials, 28, 869, 10.1016/j.biomaterials.2006.09.047 Kim, 2010, A drug-loaded aptamer–gold nanoparticle bioconjugate for combined ct imaging and therapy of prostate cancer, ACS Nano, 4, 3689, 10.1021/nn901877h Xiao, 2012, DNA self-assembly of targeted near-infrared-responsive gold nanoparticles for cancer thermo-chemotherapy, Angew. Chem. Int. Ed., 51, 11853, 10.1002/anie.201204018 Werner, 2011, Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis, Biomaterials, 32, 8548, 10.1016/j.biomaterials.2011.07.067 Marrache, 2012, Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics, Proc. Natl. Acad. Sci. U. S. A., 109, 16288, 10.1073/pnas.1210096109 Kirpotin, 2006, Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models, Cancer Res., 66, 6732, 10.1158/0008-5472.CAN-05-4199 Brennan, 2004, Preclinical safety testing of biotechnology-derived pharmaceuticals — understanding the issues and addressing the challenges, Mol. Biotechnol., 27, 59, 10.1385/MB:27:1:59 Weinberg, 2005, Development and regulation of monoclonal antibody products: challenges and opportunities, Cancer Metastasis Rev., 24, 569, 10.1007/s10555-005-6196-y Simard, 2010, In vivo evaluation of pH-sensitive polymer-based immunoliposomes targeting the CD33 antigen, Mol. Pharm., 7, 1098, 10.1021/mp900261m Ansell, 1996, 3-(2-Pyridyldithio)propionic acid hydrazide as a cross-linker in the formation of liposome–antibody conjugates, Bioconjug. Chem., 7, 490, 10.1021/bc960036+ Koning, 2001, Pharmacokinetics of differently designed immunoliposome formulations in rats with or without hepatic colon cancer metastases, Pharm. Res., 18, 1291, 10.1023/A:1013085811044 Jain, 2010, Advances in the field of nanooncology, BMC Med., 8, 83, 10.1186/1741-7015-8-83 Nemunaitis, 2008, Potential of Advexin®: a p53 gene-replacement therapy in Li–Fraumeni syndrome, Future Oncol., 4, 759, 10.2217/14796694.4.6.759 Nemunaitis, 2009, A phase I study of escalating doses of SGT-53 for intravenous infusion of patients with advanced solid tumors, Mol. Ther., 17, S226, 10.1016/S1525-0016(16)38951-1 Mamot, 2012, Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study, Lancet Oncol., 13, 1234, 10.1016/S1470-2045(12)70476-X Chou, 2011, Strategies for the intracellular delivery of nanoparticles, Chem. Soc. Rev., 40, 233, 10.1039/C0CS00003E Choi, 2010, Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles, Proc. Natl. Acad. Sci. U. S. A., 107, 1235, 10.1073/pnas.0914140107 Sahoo, 2004, Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer, Int. J. Cancer, 112, 335, 10.1002/ijc.20405 Colas, 2008, The eleven-year switch of peptide aptamers, J. Biol., 7, 2, 10.1186/jbiol64 Meng, 2010, A membrane-associated thioredoxin required for plant growth moves from cell to cell, suggestive of a role in intercellular communication, Proc. Natl. Acad. Sci. U. S. A., 107, 3900, 10.1073/pnas.0913759107 Xiao, 2012, Aptamer-functionalized nanoparticles for medical applications: challenges and opportunities, ACS Nano, 6, 3670, 10.1021/nn301869z Bendele, 1998, Renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins, Toxicol. Sci., 42, 152, 10.1093/toxsci/42.2.152 Webster, 2007, PEGylated proteins: evaluation of their safety in the absence of definitive metabolism studies, Drug Metab. Dispos., 35, 9, 10.1124/dmd.106.012419 Burke, 2002, Cilengitide targeting of αvβ3 integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts, Cancer Res., 62, 4263 Goodman, 2002, Nanomolar small molecule inhibitors for αvβ6, αvβ5, and αvβ3 integrins, J. Med. Chem., 45, 1045, 10.1021/jm0102598 Colombo, 2002, Structure–activity relationships of linear and cyclic peptides containing the NGR tumor-homing motif, J. Biol. Chem., 277, 47891, 10.1074/jbc.M207500200 Laakkonen, 2002, A tumor-homing peptide with a targeting specificity related to lymphatic vessels, Nat. Med., 8, 751, 10.1038/nm720 Porkka, 2002, A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo, Proc. Natl. Acad. Sci. U. S. A., 99, 7444, 10.1073/pnas.062189599 Roth, 2012, Transtumoral targeting enabled by a novel neuropilin-binding peptide, Oncogene, 31, 3754, 10.1038/onc.2011.537 Luo, 2010, LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors, Int. J. Pharm., 385, 150, 10.1016/j.ijpharm.2009.10.014 Sugahara, 2010, Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs, Science, 328, 1031, 10.1126/science.1183057 Slovin, 2005, Targeting novel antigens for prostate cancer treatment: focus on prostate-specific membrane antigen, Expert Opin. Ther. Targets, 9, 561, 10.1517/14728222.9.3.561 Pasqualini, 2000, Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis, Cancer Res., 60, 722 Zhang, 2008, PLGA nanoparticle–peptide conjugate effectively targets intercellular cell-adhesion molecule-1, Bioconjug. Chem., 19, 145, 10.1021/bc700227z Hild, 2010, G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake, Proc. Natl. Acad. Sci. U. S. A., 107, 10667, 10.1073/pnas.0912782107 Pinheiro, 2012, Synthetic genetic polymers capable of heredity and evolution, Science, 336, 341, 10.1126/science.1217622 Zhu, 2011, Bioresponsive controlled release using mesoporous silica nanoparticles capped with aptamer-based molecular gate, J. Am. Chem. Soc., 133, 1278, 10.1021/ja110094g Lapointe, 2006, Differential abilities of mouse liver parenchymal and nonparenchymal cells in HDL and LDL (native and oxidized) association and cholesterol efflux, Biochem. Cell Biol., 84, 250, 10.1139/o05-172 Nahvi, 2002, Genetic control by a metabolite binding mRNA, Chem. Biol., 9, 1043, 10.1016/S1074-5521(02)00224-7 Mironov, 2002, Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria, Cell, 111, 747, 10.1016/S0092-8674(02)01134-0 Winkler, 2002, Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression, Nature, 419, 952, 10.1038/nature01145 Oliphant, 1989, Defining the sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: analysis of yeast GCN4 protein, Mol. Cell. Biol., 9, 2944, 10.1128/MCB.9.7.2944 Tuerk, 1990, Systematic evolution of ligands by exponential enrichment — RNA ligands to bacteriophage-T4 DNA-polymerase, Science, 249, 505, 10.1126/science.2200121 Ellington, 1990, In vitro selection of RNA molecules that bind specific ligands, Nature, 346, 818, 10.1038/346818a0 Daniels, 2003, A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment, Proc. Natl. Acad. Sci. U. S. A., 100, 15416, 10.1073/pnas.2136683100 Xiao, 2012, Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection, ACS Nano, 6, 696, 10.1021/nn204165v Mi, 2010, In vivo selection of tumor-targeting RNA motifs, Nat. Chem. Biol., 6, 22, 10.1038/nchembio.277 Farokhzad, 2004, Nanoparticle–aptamer bioconjugates: a new approach for targeting prostate cancer cells, Cancer Res., 64, 7668, 10.1158/0008-5472.CAN-04-2550 Bagalkot, 2006, An aptamer–doxorubicin physical conjugate as a novel targeted drug-delivery platform, Angew. Chem. Int. Ed., 45, 8149, 10.1002/anie.200602251 Farokhzad, 2006, Nanomedicine: developing smarter therapeutic and diagnostic modalities, Adv. Drug Deliv. Rev., 58, 1456, 10.1016/j.addr.2006.09.011 Keefe, 2010, Aptamers as therapeutics, Nat. Rev. Drug Discov., 9, 537, 10.1038/nrd3141 Lee, 2006, Aptamer therapeutics advance, Curr. Opin. Chem. Biol., 10, 282, 10.1016/j.cbpa.2006.03.015 Kleiner, 2010, In vitro selection of a DNA-templated small-molecule library reveals a class of macrocyclic kinase inhibitors, J. Am. Chem. Soc., 132, 11779, 10.1021/ja104903x Melkko, 2004, Encoded self-assembling chemical libraries, Nat. Biotechnol., 22, 568, 10.1038/nbt961 Hilgenbrink, 2005, Folate receptor-mediated drug targeting: from therapeutics to diagnostics, J. Pharm. Sci., 94, 2135, 10.1002/jps.20457 Markert, 2008, Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue, Anticancer Res., 28, 3567 van Dam, 2011, Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-[alpha] targeting: first in-human results, Nat. Med., 17, 1315, 10.1038/nm.2472 Fisher, 2008, Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors, J. Nucl. Med., 49, 899, 10.2967/jnumed.107.049478 Parker, 2005, Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay, Anal. Biochem., 338, 284, 10.1016/j.ab.2004.12.026 Kamen, 1988, Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles, J. Biol. Chem., 263, 13602, 10.1016/S0021-9258(18)68284-5 Smith, 2003, Delivery of bioactive molecules to mitochondria in vivo, Proc. Natl. Acad. Sci. U. S. A., 100, 5407, 10.1073/pnas.0931245100 Zhang, 2010, Recent developments in carbohydrate-decorated targeted drug/gene delivery, Med. Res. Rev., 30, 270 Hashida, 2001, Cell-specific delivery of genes with glycosylated carriers, Adv. Drug Deliv. Rev., 52, 187, 10.1016/S0169-409X(01)00209-5 Bergen, 2006, Gold nanoparticles as a versatile platform for optimizing physicochemical parameters for targeted drug delivery, Macromol. Biosci., 6, 506, 10.1002/mabi.200600075 Leckband, 2011, Novel functions and binding mechanisms of carbohydrate-binding proteins determined by force measurements, Curr. Protein Pept. Sci., 12, 743, 10.2174/138920311798841735 André, 2000, Lectin-mediated drug targeting: selection of valency, sugar type (Gal/Lac), and spacer length for cluster glycosides as parameters to distinguish ligand binding to C-type asialoglycoprotein receptors and galectins, Pharm. Res., 17, 985, 10.1023/A:1007535506705 Seymour, 2002, Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin, J. Clin. Oncol., 20, 1668, 10.1200/JCO.20.6.1668 Duncan, 2006, Polymer conjugates as anticancer nanomedicines, Nat. Rev. Cancer, 6, 688, 10.1038/nrc1958 Hillier, 2009, Preclinical evaluation of novel glutamate–urea–lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer, Cancer Res., 69, 6932, 10.1158/0008-5472.CAN-09-1682 Matsumura, 2004, Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer, Ann. Oncol., 15, 517, 10.1093/annonc/mdh092 Senzer, 2013, Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors, Mol. Ther., 21, 1096, 10.1038/mt.2013.32 Wickham, 2012, A phase I study of MM-302, a HER2-targeted liposomal doxorubicin, Suppl. 3 Chawla, 2010, Advanced phase I/II studies of targeted gene delivery in vivo: intravenous rexin-G for gemcitabine-resistant metastatic pancreatic cancer, Mol. Ther., 18, 435, 10.1038/mt.2009.228 Chawla, 2009, Phase I/II and phase II studies of targeted gene delivery in vivo: intravenous rexin-G for chemotherapy-resistant sarcoma and osteosarcoma, Mol. Ther., 17, 1651, 10.1038/mt.2009.126 Galanis, 2008, Phase I Trial of a Pathotropic Retroviral Vector Expressing a Cytocidal Cyclin G1 Construct (Rexin-G) in Patients With Advanced Pancreatic Cancer, Mol. Ther., 16, 979, 10.1038/mt.2008.29 van der Meel, 2013, Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status, Adv. Drug Deliv. Rev., 65, 1284, 10.1016/j.addr.2013.08.012 Rochlitz, 2011, A phase I study of doxorubicin-loaded anti-EGFR immunoliposomes in patients with advanced solid tumors, Onkologie, 34, 109-109 Burgess, 2010, On firm ground: IP protection of therapeutic nanoparticles, Nat. Biotechnol., 28, 1267, 10.1038/nbt.1725 Daniels, 2006, The transferrin receptor part I: biology and targeting with cytotoxic antibodies for the treatment of cancer, Clin. Immunol., 121, 144, 10.1016/j.clim.2006.06.010 Yurkovetskiy, 2009, XMT-1001, a novel polymeric camptothecin pro-drug in clinical development for patients with advanced cancer, Adv. Drug Deliv. Rev., 61, 1193, 10.1016/j.addr.2009.01.007 Danhauser-Riedl, 1993, Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOX-OXD), Invest. New Drugs, 11, 187, 10.1007/BF00874153 Schoemaker, 2002, A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin, Br. J. Cancer, 87, 608, 10.1038/sj.bjc.6600516 Lorusso, 2007, Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia (‘hand–foot’ syndrome), Ann. Oncol., 18, 1159, 10.1093/annonc/mdl477 Szebeni, 2011, Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention, Adv. Drug Deliv. Rev., 63, 1020, 10.1016/j.addr.2011.06.017 Rajasekaran, 2005, Is prostate-specific membrane antigen a multifunctional protein?, Am. J. Physiol. Cell Physiol., 288, C975, 10.1152/ajpcell.00506.2004 Ong, 2012, Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing, Expert. Rev. Mol. Diagn., 12, 593, 10.1586/erm.12.59 Desai, 2009, SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients, Transl. Oncol., 2, 59, 10.1593/tlo.09109