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

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Abstract

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

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References

  • Abakumov MA, Nukolova NV, Sokolsky-Papkov M, et al. (2015) VEGF-targeted magnetic nanoparticles for MRI visualization of brain tumor. Nanomedicine 11:825–833

    CAS  PubMed  Google Scholar 

  • Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200:629–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Agrahari V, Agrahari V, Mitra AK (2016a) Nanocarrier fabrication and macromolecule drug delivery: challenges and opportunities. Ther Deliv 7:257–278

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. (2013) Liposome: classification, preparation, and applications. Nanoscale Res Lett 8:102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Anajafi T, Mallik S (2015) Polymersome-based drug-delivery strategies for cancer therapeutics. Ther Deliv 6:521–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arvizo R, Bhattacharya R, Mukherjee P (2010) Gold nanoparticles: opportunities and challenges in nanomedicine. Expert Opin Drug Deliv 7:753–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azad TD, Pan J, Connolly ID, et al. (2015) Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurg Focus 38:E9

    Article  PubMed  PubMed Central  Google Scholar 

  • Bagherifam S, Skjeldal FM, Griffiths G, et al. (2015) pH-responsive nano carriers for doxorubicin delivery. Pharm Res 32:1249–1263

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Beg S, Rizwan M, Sheikh AM, et al. (2011) Advancement in carbon nanotubes: basics, biomedical applications and toxicity. J Pharm Pharmacol 63:141–163

    Article  CAS  PubMed  Google Scholar 

  • Begley DJ, Brightman MW (2003) Structural and functional aspects of the blood-brain barrier. Prog Drug Res 61:39–78

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bhowmik A, Khan R, Ghosh MK (2015) Blood brain barrier: a challenge for effectual therapy of brain tumors. Biomed Res Int 2015:320941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Braccioli L, van Velthoven C, Heijnen CJ (2014) Exosomes: a new weapon to treat the central nervous system. Mol Neurobiol 49:113–119

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Cabuzu D, Cirja A, Puiu R, et al. (2015) Biomedical applications of gold nanoparticles. Curr Top Med Chem 15:1605–1613

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Cheng Y, Morshed RA, Auffinger B, et al. (2014b) Multifunctional nanoparticles for brain tumor imaging and therapy. Adv Drug Deliv Rev 66:42–57

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Davis ME, Chen ZG, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782

    Article  CAS  PubMed  Google Scholar 

  • Demeule M, Poirier J, Jodoin J, et al. (2002) High transcytosis of melanotransferrin (P97) across the blood-brain barrier. J Neurochem 83:924–933

    Article  CAS  PubMed  Google Scholar 

  • Deshpande PP, Biswas S, Torchilin VP (2013) Current trends in the use of liposomes for tumor targeting. Nanomedicine (London) 8:1509–1528

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Gabathuler R (2010) Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol Dis 37:48–57

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Grapp M, Wrede A, Schweizer M, et al. (2013) Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nat Commun 4:2123

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Gao X, Su L, et al. (2011) Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials 32:8010–8020

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heitz F, Morris MC, Divita G (2009) Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics. Br J Pharmacol 157:195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herve F, Ghinea N, Scherrmann JM (2008) CNS delivery via adsorptive transcytosis. AAPS J 10:455–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: progress and challenges. Polymer 49:1993–2007

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Ji SR, Liu C, Zhang B, et al. (2010) Carbon nanotubes in cancer diagnosis and therapy. Biochim Biophys Acta 1806:29–35

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Joh DY, Sun L, Stangl M, et al. (2013) Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization. PLoS One 8:e62425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Kabanov AV, Vinogradov SV (2009) Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed Eng 48:5418–5429

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Katakowski M, Chopp M (2016) Exosomes as tools to suppress primary brain tumor. Cell Mol Neurobiol 36:343–352

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koren E, Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18:385–393

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laron Z (2009) Insulin and the brain. Arch Physiol Biochem 115:112–116

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Lipinski CA (2004) Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1:337–341

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Lu W (2012) Recent advances in brain tumor-targeted nano-drug delivery systems. Expert Opin Drug Deliv 9:671–686

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Lu Y, Park K (2013) Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int J Pharm 453:198–214

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi K, Hadjipanayis CG (2014) The application of magnetic nanoparticles for the treatment of brain tumors. Front Chem 2:109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Meyers JD, Doane T, Burda C, et al. (2013) Nanoparticles for imaging and treating brain cancer. Nanomedicine (London) 8:123–143

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    PubMed  PubMed Central  Google Scholar 

  • Mitra AK, Agrahari V, Mandal A, et al. (2015) Novel delivery approaches for cancer therapeutics. J Control Release 219:248–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Morachis JM, Mahmoud EA, Almutairi A (2012) Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacol Rev 64:505–519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–1003

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Nishida N, Yano H, Nishida T, et al. (2006) Angiogenesis in cancer. Vasc Health Risk Manag 2:213–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Oerlemans C, Bult W, Bos M, et al. (2010) Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 27:2569–2589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohgaki H, Kleihues P (2013) The definition of primary and secondary glioblastoma. Clin Cancer Res 19:764–772

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Riehemann K, Schneider SW, Luger TA, et al. (2009) Nanomedicine--challenge and perspectives. Angew Chem 48:872–897

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Salmaso S, Caliceti P (2013) Stealth properties to improve therapeutic efficacy of drug nanocarriers. J Drug Deliv 2013:374252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sanhai WR, Sakamoto JH, Canady R, et al. (2008) Seven challenges for nanomedicine. Nat Nanotechnol 3:242–244

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30

    Article  PubMed  Google Scholar 

  • Somani S, Dufes C (2014) Applications of dendrimers for brain delivery and cancer therapy. Nanomedicine (London) 9:2403–2414

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Torchilin VP (2014) Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 13:813–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay RK (2014) Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Res Int 2014:869269

    PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res 24:1405–1414

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei X, Chen X, Ying M, et al. (2014) Brain tumor-targeted drug delivery strategies. Acta Pharm Sin B 4:193–201

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Wong HL, Wu XY, Bendayan R (2012) Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 64:686–700

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Yan Z, Wei D, et al. (2013) Tumor-penetrating peptide functionalization enhances the anti-glioblastoma effect of doxorubicin liposomes. Nanotechnology 24:405101

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Yao J, Hsu CH, Li Z, et al. (2015b) Magnetic resonance nano-theranostics for glioblastoma multiforme. Curr Pharm Des 21:5256–5266

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Zhang TT, Li W, Meng G, et al. (2016b) Strategies for transporting nanoparticles across the blood-brain barrier. Biomater Sci 4:219–229

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences, University of Missouri Kansas City, Kansas City, MO, 64108, USA

    Jianing Meng & Vivek Agrahari

  2. Hough Ear Institute, Oklahoma City, OK, 73112, USA

    Ibrahima Youm

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  1. Jianing Meng
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  2. Vivek Agrahari
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Jianing Meng and Vivek Agrahari contributed equally.

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Meng, J., Agrahari, V. & Youm, I. Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology. J Neuroimmune Pharmacol 12, 84–98 (2017). https://doi.org/10.1007/s11481-016-9698-1

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