Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology

Abakumov MA, Nukolova NV, Sokolsky-Papkov M, et al. (2015) VEGF-targeted magnetic nanoparticles for MRI visualization of brain tumor. Nanomedicine 11:825–833 Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200:629–638 Agrahari V, Zhang C, Zhang T, et al. (2014) Hyaluronidase-sensitive nanoparticle templates for triggered release of HIV/AIDS microbicide in vitro. AAPS J 16:181–193 Agrahari V, Agrahari V, Mitra AK (2016a) Nanocarrier fabrication and macromolecule drug delivery: challenges and opportunities. Ther Deliv 7:257–278 Agrahari V, Agrahari V, Hung WT, et al. (2016b) Composite nanoformulation therapeutics for long-term ocular delivery of macromolecules. Mol Pharm. doi:10.1021/acs.molpharmaceut.5b00828 Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. (2013) Liposome: classification, preparation, and applications. Nanoscale Res Lett 8:102 Anajafi T, Mallik S (2015) Polymersome-based drug-delivery strategies for cancer therapeutics. Ther Deliv 6:521–534 Arvizo R, Bhattacharya R, Mukherjee P (2010) Gold nanoparticles: opportunities and challenges in nanomedicine. Expert Opin Drug Deliv 7:753–763 Azad TD, Pan J, Connolly ID, et al. (2015) Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurg Focus 38:E9 Bagherifam S, Skjeldal FM, Griffiths G, et al. (2015) pH-responsive nano carriers for doxorubicin delivery. Pharm Res 32:1249–1263 Bai CZ, Choi S, Nam K, et al. (2013) Arginine modified PAMAM dendrimer for interferon beta gene delivery to malignant glioma. Int J Pharm 445:79–87 Baklaushev VP, Nukolova NN, Khalansky AS, et al. (2015) Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1. Drug Deliv 22:276–285 Beg S, Rizwan M, Sheikh AM, et al. (2011) Advancement in carbon nanotubes: basics, biomedical applications and toxicity. J Pharm Pharmacol 63:141–163 Begley DJ, Brightman MW (2003) Structural and functional aspects of the blood-brain barrier. Prog Drug Res 61:39–78 Bell RD, Sagare AP, Friedman AE, et al. (2007) Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J Cereb Blood Flow Metab 27:909–918 Bhaskar S, Tian F, Stoeger T, et al. (2010) Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging. Part Fibre Toxicol 7:3 Bhowmik A, Khan R, Ghosh MK (2015) Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int 2015:320941 Biswas S, Kumari P, Lakhani PM, et al. (2016) Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci 83:184–202 Braccioli L, van Velthoven C, Heijnen CJ (2014) Exosomes: a new weapon to treat the central nervous system. Mol Neurobiol 49:113–119 Butt AM, Jones HC, Abbott NJ (1990) Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J Physiol 429:47–62 Byeon HJ, Thao le Q, Lee S, et al. (2016) Doxorubicin-loaded nanoparticles consisted of cationic- and mannose-modified-albumins for dual-targeting in brain tumors. J Control Release 225:301–313 Cabuzu D, Cirja A, Puiu R, et al. (2015) Biomedical applications of gold nanoparticles. Curr Top Med Chem 15:1605–1613 Chacko AM, Li C, Pryma DA, et al. (2013) Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide. Expert Opin Drug Deliv 10:907–926 Chen PY, Liu HL, Hua MY, et al. (2010) Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment. Neuro-Oncology 10:1050–1060 Chen YC, Chiang CF, Chen LF, et al. (2014) Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system. Biomaterials 35:4066–4081 Chen B, He XY, Yi XQ, et al. (2015) Dual-peptide-functionalized albumin-based nanoparticles with ph-dependent self-assembly behavior for drug delivery. ACS Appl Mater Interfaces 7:15148–15153 Cheng R, Meng F, Deng C, et al. (2013) Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials 34:3647–3657 Cheng W, Gu L, Ren W, et al. (2014a) Stimuli-responsive polymers for anti-cancer drug delivery. Mater Sci Eng C Mater Biol Appl 45:600–608 Cheng Y, Morshed RA, Auffinger B, et al. (2014b) Multifunctional nanoparticles for brain tumor imaging and therapy. Adv Drug Deliv Rev 66:42–57 Cheng Y, Dai Q, Morshed RA, et al. (2014c) Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging. Small 10:5137–5150 Chowdhury SM, Surhland C, Sanchez Z, et al. (2015) Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. Nanomedicine 11:109–118 Coloma MJ, Lee HJ, Kurihara A, et al. (2000) Transport across the primate blood-brain barrier of a genetically engineered chimeric monoclonal antibody to the human insulin receptor. Pharm Res 17:266–274 Cui Y, Xu Q, Chow PK, et al. (2013) Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials 34:8511–8520 Daniels TR, Bernabeu E, Rodriguez JA, et al. (2012) The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta 1820:291–317 Davis ME, Chen ZG, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782 Demeule M, Poirier J, Jodoin J, et al. (2002) High transcytosis of melanotransferrin (P97) across the blood-brain barrier. J Neurochem 83:924–933 Deshpande PP, Biswas S, Torchilin VP (2013) Current trends in the use of liposomes for tumor targeting. Nanomedicine (London) 8:1509–1528 Dixit S, Novak T, Miller K, et al. (2015a) Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors. Nanoscale 7:1782–1790 Dixit S, Miller K, Zhu Y, et al. (2015b) Dual receptor-targeted theranostic nanoparticles for localized delivery and activation of photodynamic therapy drug in glioblastomas. Mol Pharm 12:3250–3260 Du J, Lu WL, Ying X, et al. (2009) Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood-brain barrier and survival of brain tumor-bearing animals. Mol Pharm 6:905–917 Dwivedi N, Shah J, Mishra V, et al. (2016) Dendrimer-mediated approaches for the treatment of brain tumor. J Biomater Sci Polym Ed 27:557–580 Engin K, Leeper DB, Cater JR, et al. (1995) Extracellular pH distribution in human tumours. Int J Hyperth : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 11:211–216 Ernsting MJ, Murakami M, Roy A, et al. (2013) Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Release : official journal of the Controlled Release Society 172:782–794 Fang Liu XL, Li-Yuan Z, Qing-Ru S, et al. (2016) Stimuli-responsive nanocarriers for drug delivery to the central nervous system. Curr Nanosci 12:14 Fang JH, Lai YH, Chiu TL, et al. (2014) Magnetic core-shell nanocapsules with dual-targeting capabilities and co-delivery of multiple drugs to treat brain gliomas. Adv Healthcare Mater 3:1250–1260 Fang JH, Chiu TL, Huang WC, et al. (2016) Dual-targeting lactoferrin-conjugated polymerized magnetic polydiacetylene-assembled nanocarriers with self-responsive fluorescence/magnetic resonance imaging for in vivo brain tumor therapy. Adv Healthcare Mater 5:688–695 Gabathuler R (2010) Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol Dis 37:48–57 Gao HL, Pang ZQ, Fan L, et al. (2010) Effect of lactoferrin- and transferrin-conjugated polymersomes in brain targeting: in vitro and in vivo evaluations. Acta Pharmacol Sin 31:237–243 Gao JQ, Lv Q, Li LM, et al. (2013) Glioma targeting and blood-brain barrier penetration by dual-targeting doxorubincin liposomes. Biomaterials 34:5628–5639 Ghose AK, Herbertz T, Hudkins RL, et al. (2012) Knowledge-based, central nervous system (CNS) lead selection and lead optimization for CNS drug discovery. ACS Chem Neurosci 3:50–68 Grapp M, Wrede A, Schweizer M, et al. (2013) Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nat Commun 4:2123 Gu G, Hu Q, Feng X, et al. (2014) PEG-PLA nanoparticles modified with APTEDB peptide for enhanced anti-angiogenic and anti-glioma therapy. Biomaterials 35:8215–8226 Guo J, Gao X, Su L, et al. (2011) Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials 32:8010–8020 He H, Li Y, Jia XR, et al. (2011) PEGylated Poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials 32:478–487 He H, David A, Chertok B, et al. (2013) Magnetic nanoparticles for tumor imaging and therapy: a so-called theranostic system. Pharm Res 30:2445–2458 Heitz F, Morris MC, Divita G (2009) Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics. Br J Pharmacol 157:195–206 Herve F, Ghinea N, Scherrmann JM (2008) CNS delivery via adsorptive transcytosis. AAPS J 10:455–472 Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: progress and challenges. Polymer 49:1993–2007 Huang R, Ke W, Han L, et al. (2011a) Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration. Biomaterials 32:2399–2406 Huang S, Li J, Han L, et al. (2011b) Dual targeting effect of Angiopep-2-modified, DNA-loaded nanoparticles for glioma. Biomaterials 32:6832–6838 Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1:297–315 Jain A, Jain A, Garg NK, Tyagi RK, et al. (2015) Surface engineered polymeric nanocarriers mediate the delivery of transferrin-methotrexate conjugates for an improved understanding of brain cancer. Acta Biomater 24:140–151 Ji SR, Liu C, Zhang B, et al. (2010) Carbon nanotubes in cancer diagnosis and therapy. Biochim Biophys Acta 1806:29–35 Jiang W, Xie H, Ghoorah D, et al. (2012) Conjugation of functionalized SPIONs with transferrin for targeting and imaging brain glial tumors in rat model. PLoS One 7:e37376 Jiang L, Zhou Q, Mu K, et al. (2013) pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin for MR and fluorescence imaging of glioma in rats. Biomaterials 34:7418–7428 Jiang X, Xin H, Ren Q, et al. (2014) Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment. Biomaterials 35:518–529 Joh DY, Sun L, Stangl M, et al. (2013) Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization. PLoS One 8:e62425 Johnsen KB, Gudbergsson JM, et al. (2014) A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta 1846:75–87 Kabanov AV, Vinogradov SV (2009) Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed Eng 48:5418–5429 Kafa H, Wang JT, Rubio N, et al. (2016) Translocation of LRP1 targeted carbon nanotubes of different diameters across the blood-brain barrier in vitro and in vivo. J Control Release 225:217–229 Karim R, Palazzo C, Evrard B, et al. (2016) Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art. J Control Release 227:23–37 Katakowski M, Chopp M (2016) Exosomes as tools to suppress primary brain tumor. Cell Mol Neurobiol 36:343–352 Keller S, Ridinger J, Rupp AK, et al. (2011) Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 9:86 Kooijmans SA, Vader P, van Dommelen SM, et al. (2012) Exosome mimetics: a novel class of drug delivery systems. Int J Nanomedicine 7:1525–1541 Koren E, Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18:385–393 Krishnamoorthy B, Karanam V, Chellan VR, et al. (2014) Polymersomes as an effective drug delivery system for glioma--a review. J Drug Target 22:469–477 Kuang Y, An S, Guo Y, et al. (2013) T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting. Int J Pharm 454:11–20 Kuo YC, Lee CH (2016) Dual targeting of solid lipid nanoparticles grafted with 83-14 MAb and anti-EGF receptor for malignant brain tumor therapy. Life Sci 146:222–231 Laquintana V, Trapani A, Denora N, et al. (2009) New strategies to deliver anticancer drugs to brain tumors. Expert Opin Drug Deliv 6:1017–1032 Laron Z (2009) Insulin and the brain. Arch Physiol Biochem 115:112–116 Laschinger M, Engelhardt B (2000) Interaction of alpha4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro. J Neuroimmunol 102:32–43 Li Y, He H, Jia X, et al. (2012) A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials 33:3899–3908 Li AJ, Zheng YH, Liu GD, et al. (2015) Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles. Mol Med Rep 11:3078–3086 Li L, Di X, Zhang S, et al. (2016) Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting. Colloids Surf B: Biointerfaces 141:260–267 Lipinski CA (2004) Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1:337–341 Liu Y, Lu W (2012) Recent advances in brain tumor-targeted nano-drug delivery systems. Expert Opin Drug Deliv 9:671–686 Liu Y, Ran R, Chen J, et al. (2014) Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting. Biomaterials 35:4835–4847 Liu Y, Mei L, Yu Q, et al. (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 7:16792–16801 Liu H, Zhang J, Chen X, et al. (2016) Application of iron oxide nanoparticles in glioma imaging and therapy: from bench to bedside. Nanoscale 8:7808–7826 Locatelli E, Naddaka M, Uboldi C, et al. (2014) Targeted delivery of silver nanoparticles and alisertib: in vitro and in vivo synergistic effect against glioblastoma. Nanomedicine (London) 9:839–849 Lu Y, Park K (2013) Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int J Pharm 453:198–214 Lu W, Sun Q, Wan J, et al. (2006) Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration. Cancer Res 66:11878–11887 Lu YJ, Wei KC, Ma CC, et al. (2012) Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes. Colloids Surf B: Biointerfaces 89:1–9 Mahmoudi K, Hadjipanayis CG (2014) The application of magnetic nanoparticles for the treatment of brain tumors. Front Chem 2:109 Maletinska L, Blakely EA, Bjornstad KA, et al. (2000) Human glioblastoma cell lines: levels of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein. Cancer Res 60:2300–2303 Maya S, Sarmento B, Nair A, et al. (2013) Smart stimuli sensitive nanogels in cancer drug delivery and imaging: a review. Curr Pharm Des 19:7203–7218 Meng J, Zhang T, Agrahari V, et al. (2014) Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention. Nanomedicine (London) 9:1595–1612 Meyers JD, Doane T, Burda C, et al. (2013) Nanoparticles for imaging and treating brain cancer. Nanomedicine (London) 8:123–143 Meyers JD, Cheng Y, Broome AM, et al. (2015) Peptide-targeted gold nanoparticles for photodynamic therapy of brain cancer. Part Part Syst Charact 32:448–457 Mikitsh JL, Chacko AM (2014) Pathways for small molecule delivery to the central nervous system across the blood-brain barrier. Perspect Medicin Chem 6:11–24 Mitra AK, Agrahari V, Mandal A, et al. (2015) Novel delivery approaches for cancer therapeutics. J Control Release 219:248–268 Miura Y, Takenaka T, Toh K, et al. (2013) Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier. ACS Nano 7:8583–8592 Morachis JM, Mahmoud EA, Almutairi A (2012) Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacol Rev 64:505–519 Mu K, Zhang S, Ai T, et al. (2015) Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas. Mol Imaging 14:1–12. Munyendo WL, Lv H, Benza-Ingoula H, et al. (2012) Cell penetrating peptides in the delivery of biopharmaceuticals. Biomolecules 2:187–202 Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–1003 Ni D, Zhang J, Bu W, et al. (2014) Dual-targeting upconversion nanoprobes across the blood-brain barrier for magnetic resonance/fluorescence imaging of intracranial glioblastoma. ACS Nano 8:1231–1242 Nishida N, Yano H, Nishida T, et al. (2006) Angiogenesis in cancer. Vasc Health Risk Manag 2:213–219 Niu J, Wang A, Ke Z, et al. (2014) Glucose transporter and folic acid receptor-mediated Pluronic P105 polymeric micelles loaded with doxorubicin for brain tumor treating. J Drug Target 22:712–723 Oerlemans C, Bult W, Bos M, et al. (2010) Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 27:2569–2589 Ohgaki H, Kleihues P (2013) The definition of primary and secondary glioblastoma. Clin Cancer Res 19:764–772 Ohtsuki S, Terasaki T (2007) Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm Res 24:1745–1758 Oldendorf WH, Cornford ME, Brown WJ (1977) The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1:409–417 Ostrom QT, Gittleman H, de Blank PM, et al. (2016) American brain tumor association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncology 18(Suppl 1):i1–i50 Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102 Pang Z, Feng L, Hua R, et al. (2010) Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol Pharm 7:1995–2005 Pang Z, Gao H, Yu Y, et al. (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22:1171–1180 Pardridge WM (2003) Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv 3:90–105, 151 Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14 Persidsky Y, Ramirez SH, Haorah J, et al. (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J NeuroImmune Pharmacol 1:223–236 Qin Y, Chen H, Yuan W, et al. (2011) Liposome formulated with TAT-modified cholesterol for enhancing the brain delivery. Int J Pharm 419:85–95 Recht L, Torres CO, Smith TW, et al. (1990) Transferrin receptor in normal and neoplastic brain tissue: implications for brain-tumor immunotherapy. J Neurosurg 72:941–945 Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217 Ren J, Shen S, Wang D, et al. (2012) The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials 33:3324–3333 Riehemann K, Schneider SW, Luger TA, et al. (2009) Nanomedicine--challenge and perspectives. Angew Chem 48:872–897 Ronaldson PT, Davis TP (2012) Blood-brain barrier integrity and glial support: mechanisms that can be targeted for novel therapeutic approaches in stroke. Curr Pharm Des 18:3624–3644 Ruan S, Yuan M, Zhang L, et al. (2015a) Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials 37:425–435 Ruan S, Chen J, Cun X, et al. (2015b) Noninvasive in vivo diagnosis of brain glioma using rgd-decorated fluorescent carbonaceous nanospheres. J Biomed Nanotechnol 11:2148–2157 Ruiqing Liu SL, Cun J, Xin W, et al. (2015) Paramagnetic, pH and temperature-sensitive polymeric particles for anticancer drug delivery and brain tumor magnetic resonance imaging. RSC Adv 5:9 Salmaso S, Caliceti P (2013) Stealth properties to improve therapeutic efficacy of drug nanocarriers. J Drug Deliv 2013:374252 Sanhai WR, Sakamoto JH, Canady R, et al. (2008) Seven challenges for nanomedicine. Nat Nanotechnol 3:242–244 Shevtsov MA, Nikolaev BP, Yakovleva LY, et al. (2014) Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION-EGF) for targeting brain tumors. Int J Nanomedicine 9:273–287 Shevtsov MA, Nikolaev BP, Yakovleva LY, et al. (2015) Recombinant interleukin-1 receptor antagonist conjugated to superparamagnetic iron oxide nanoparticles for theranostic targeting of experimental glioblastoma. Neoplasia 17:32–42 Shukla R, Bansal V, Chaudhary M, et al. (2005) Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir 21:10644–10654 Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30 Somani S, Dufes C (2014) Applications of dendrimers for brain delivery and cancer therapy. Nanomedicine (London) 9:2403–2414 Somani S, Blatchford DR, Millington O, et al. (2014) Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain. J Control Release 188:78–86 Squire JM, Chew M, Nneji G, et al. (2001) Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? J Struct Biol 136:239–255 Torchilin VP (2014) Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 13:813–827 Tuguntaev RG, Okeke CI, Xu J, et al. (2016) Nanoscale polymersomes as anti-cancer drug carriers applied for pharmaceutical delivery. Curr Pharm Des 22:2857–2865 Ulbrich K, Knobloch T, Kreuter J (2011) Targeting the insulin receptor: nanoparticles for drug delivery across the blood-brain barrier (BBB). J Drug Target 19:125–132 Uotani S, Bjorbaek C, Tornoe J, et al. (1999) Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation. Diabetes 48:279–286 Upadhyay RK (2014) Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Res Int 2014:869269 van Tellingen O, Yetkin-Arik B, de Gooijer MC, et al. (2015) Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat 19:1–12 van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res 24:1405–1414 Wager TT, Chandrasekaran RY, Hou X, et al. (2010) Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes. ACS Chem Neurosci 1:420–434 Wang F, Zhang W, Shen Y, et al. (2015) Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods. Acta Biomater 23:136–146 Wankhede M, Bouras A, Kaluzova M, et al. (2012) Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy. Expert Rev Clin Pharmacol 5:173–186 Watkins S, Robel S, Kimbrough IF, et al. (2014) Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nat Commun 5:4196 Wei X, Chen X, Ying M, et al. (2014) Brain tumor-targeted drug delivery strategies. Acta Pharm Sin B 4:193–201 Wei X, Gao J, Zhan C, et al. (2015) Liposome-based glioma targeted drug delivery enabled by stable peptide ligands. J Control Release 218:13–21 Wong HL, Wu XY, Bendayan R (2012) Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 64:686–700 Yang Y, Yan Z, Wei D, et al. (2013) Tumor-penetrating peptide functionalization enhances the anti-glioblastoma effect of doxorubicin liposomes. Nanotechnology 24:405101 Yang ZZ, Li JQ, Wang ZZ, et al. (2014) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–5239 Yang T, Martin P, Fogarty B, et al. (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio Rerio. Pharm Res 32:2003–2014 Yao H, Wang K, Wang Y, et al. (2015a) Enhanced blood-brain barrier penetration and glioma therapy mediated by a new peptide modified gene delivery system. Biomaterials 37:345–352 Yao J, Hsu CH, Li Z, et al. (2015b) Magnetic resonance nano-theranostics for glioblastoma multiforme. Curr Pharm Des 21:5256–5266 Yoo JW, Chambers E, Mitragotri S (2010) Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Curr Pharm Des 16:2298–2307 Youm I, Agrahari V, Murowchick JB, et al. (2014) Uptake and cytotoxicity of docetaxel-loaded hyaluronic acid-grafted oily core nanocapsules in MDA-MB 231 cancer cells. Pharm Res 31:2439–2452 Zhang W, Zhang Z, Zhang Y (2011) The application of carbon nanotubes in target drug delivery systems for cancer therapies. Nanoscale Res Lett 6:555 Zhang P, Hu L, Yin Q, et al. (2012) Transferrin-conjugated polyphosphoester hybrid micelle loading paclitaxel for brain-targeting delivery: synthesis, preparation and in vivo evaluation. J Control Release 159:429–434 Zhang T, Zhang C, Agrahari V, et al. (2013) Spray drying tenofovir loaded mucoadhesive and pH-sensitive microspheres intended for HIV prevention. Antiviral Res 97:334–346 Zhang F, Lin YA, Kannan S, et al. (2015) Targeting specific cells in the brain with nanomedicines for CNS therapies. J Control Release. doi:10.1016/j.jconrel.2015.12.013 Zhang J, Chen N, Wang H, et al. (2016a) Dual-targeting superparamagnetic iron oxide nanoprobes with high and low target density for brain glioma imaging. J Colloid Interface Sci 469:86–92 Zhang TT, Li W, Meng G, et al. (2016b) Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci 4:219–229 Zhao YZ, Lin Q, Wong HL, et al. (2016) Glioma-targeted therapy using Cilengitide nanoparticles combined with UTMD enhanced delivery. J Control Release 224:112–125 Zhou Q, Mu K, Jiang L, et al. (2015) Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging. Int J Nanomedicine 10:1805–1818 Zong T, Mei L, Gao H, et al. (2014) Synergistic dual-ligand doxorubicin liposomes improve targeting and therapeutic efficacy of brain glioma in animals. Mol Pharm 11:2346–2357