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Applications of polymeric micelles with tumor targeted in chemotherapy

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Abstract

Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core–shell structure (with diameters of 10 ~ 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles’ surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

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References

  • Agut W, Brulet A, Schatz C, Taton D, Lecommandoux S (2010) pH and temperature responsive polymeric micelles and polymersomes by self-assembly of poly [2-(dimethylamino) ethyl methacrylate]-b-Poly (glutamic acid) double hydrophilic block copolymers. Langmuir 26:10546–10554

    Article  CAS  Google Scholar 

  • Alexis F, Rhee JW, Richie JP, Radovic-Moreno AF, Langer R, Farokhzad OC (2008) New frontiers in nanotechnology for cancer treatment. Urol Oncol 26:74–85

    Article  CAS  Google Scholar 

  • Bae YH (2009) Drug targeting and tumor heterogeneity. J Control Release 133:2–3

    Article  CAS  Google Scholar 

  • Böhmer MR, Klibanov AL, Tiemann K, Hall CS, Gruell H, Steinbach OC (2009) Ultrasound triggered image-guided drug delivery. Eur J Radiol 70:242–253

    Article  Google Scholar 

  • Boisseau P, Loubaton B (2011) Nanomedicine, nanotechnology in medicine. CR Phys 12:620–636

    Article  CAS  Google Scholar 

  • Brewer E, Coleman J, Lowman A (2011) Emerging technologies of polymeric nanoparticles in cancer drug delivery. J Nanomater. doi:10.1155/2011/408675

    Google Scholar 

  • Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, Terada Y, Kano MR, Miyazono K, Uesaka M, Nishiyama N, Kataoka K (2011) Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol 6:815–823. doi:10.1038/nnano.2011.166

    Article  CAS  Google Scholar 

  • Danhier F, Feron O, Préat V (2010) To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148:135–146. http://dx.doi.org/10.1016/j.jconrel.2010.08.027

  • Eckman AM, Tsakalozou E, Kang NY, Ponta A, Bae Y (2012) Drug release patterns and cytotoxicity of PEG-poly (aspartate) block copolymer micelles in cancer cells. Pharm Res 29:1755–1767

    Article  CAS  Google Scholar 

  • Finger EC, Giaccia AJ (2010) Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metast Rev 29:285–293. doi:10.1007/s10555-010-9224-5

    Article  CAS  Google Scholar 

  • Fournier E, Dufresne MH, Smith DC, Ranger M, Leroux JC (2004) A novel one-step drug-loading procedure for water-soluble amphiphilic nanocarriers. Pharm Res 21:962–968

    Article  CAS  Google Scholar 

  • Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC (2005) Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109:169–188

    Google Scholar 

  • Gong J, Chen M, Zheng Y, Wang S, Wang Y (2012) Polymeric micelles drug delivery system in oncology. J Control Release 159:312–323. http://dx.doi.org/10.1016/j.jconrel.2011.12.012

    Google Scholar 

  • Gourevich D, Gerold B, Arditti F, Xu D, Liu D, Volovick A, Wang L, Medan Y, Gnaim J, Prentice P (2012) Ultrasound activated nano-encapsulated targeted drug delivery and tumour cell poration. Nano Biotechnol Biomed Diagn Res 733:135–144

    Article  Google Scholar 

  • Grande R, Carvalho AJF (2011) Compatible ternary blends of chitosan/poly (vinyl alcohol)/poly (lactic acid) produced by oil-in-water emulsion processing. Biomacromolecules 12:907–914

    Article  CAS  Google Scholar 

  • Gullotti E, Yeo Y (2009) Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery. Mol Pharm 6:1041–1051

    Article  CAS  Google Scholar 

  • Hammond PT (2011) Virtual issue on nanomaterials for drug delivery. ACS Nano 5:681–684. doi:10.1021/Nn2003508

    Article  CAS  Google Scholar 

  • He J, Zhou Z, Fan Y, Zhou X, Du H (2011) Sustained release of low molecular weight heparin from PLGA microspheres prepared by a solid-in-oil-in-water emulsion method. J Microencapsul 28:763–770

    Article  CAS  Google Scholar 

  • Hua SH, Li YY, Liu Y, Xiao W, Li C, Huang FW, Zhang XZ, Zhuo RX (2010) Self-assembled micelles based on PEG-polypeptide hybrid copolymers for drug delivery. Macromol Rapid Comm 31:81–86. doi:10.1002/marc.200900473

    Article  CAS  Google Scholar 

  • Hui G, Ma Y, Lu X, Liang Y, Chen B, Ma J (2011) pH-responsive nano-assemblies of amino poly (glycerol methacrylate). Eur Polym J 47:1232–1239

    Article  CAS  Google Scholar 

  • Jin Q, Liu G, Ji J (2010) Preparation of reversibly photo-cross-linked nanogels from pH-responsive block copolymers and use as nanoreactors for the synthesis of gold nanoparticles. Eur Polym J 46:2120–2128

    Article  CAS  Google Scholar 

  • Jones MC, Leroux JC (1999) Polymeric micelles-a new generation of colloidal drug carriers. Eur J Pharm Biopharm 48:101–111

    Article  CAS  Google Scholar 

  • Jungnickel C, Łuczak J, Ranke J, Fernández JF, Müller A, Thöming J (2008) Micelle formation of imidazolium ionic liquids in aqueous solution. Colloid Surf A Physicochem Eng Asp 316:278–284

    Article  CAS  Google Scholar 

  • Katsogiannou M, Peng L, V Catapano C, Rocchi P (2011) Active-targeted nanotherapy strategies for prostate cancer. Curr Cancer Drug Targets 11:954–965. http://dx.doi.org/10.2174/156800911797264770

    Google Scholar 

  • Kedar U, Phutane P, Shidhaye S, Kadam V (2010) Advances in polymeric micelles for drug delivery and tumor targeting. Nanomed Nanotechnol Biol Med 6:714–729. http://dx.doi.org/10.1016/j.nano.2010.05.005

  • Kim S, Lee J (2010) Effective polymeric dispersants for vacuum, convection and freeze drying of drug nanosuspensions. Int J Pharm 397:218–224

    Article  CAS  Google Scholar 

  • Kim GJ, Nie S (2005) Targeted cancer nanotherapy. Mater Today 8:28–33

    Article  Google Scholar 

  • Kim E, Jung Y, Choi H, Yang J, Suh JS, Huh YM, Kim K, Haam S (2010a) Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex. Biomaterials 31:4592–4599

    Article  CAS  Google Scholar 

  • Kim JK, Yang SY, Lee Y, Kim Y (2010b) Functional nanomaterials based on block copolymer self-assembly. Prog Polym Sci 35:1325–1349

    Article  CAS  Google Scholar 

  • Kim S, Shi Y, Kim JY, Park K, Cheng JX (2010c) Overcoming the barriers in micellar drug delivery: loading efficiency, in vivo stability, and micelle-cell interaction. Expert Opin Drug Deliv 7:49–62. doi:10.1517/17425240903380446

    Article  CAS  Google Scholar 

  • Kwon G, Naito M, Yokoyama M, Okano T, Sakurai Y, Kataoka K (1997) Block copolymer micelles for drug delivery: loading and release of doxorubicin. J Control Release 48:195–201

    Article  CAS  Google Scholar 

  • Lee H, Fonge H, Hoang B, Reilly RM, Allen C (2010) The effects of particle size and molecular targeting on the intratumoral and subcellular distribution of polymeric nanoparticles. Mol Pharmaceut 7:1195–1208

    Article  CAS  Google Scholar 

  • Liang H, Tang J, Halliwell M (2010) Sonoporation, drug delivery, and gene therapy. P I Mech Eng H 224:343–361

    Article  Google Scholar 

  • Liao C, Sun Q, Liang B, Shen J, Shuai X (2010) Targeting EGFR-overexpressing tumor cells using Cetuximab-immunomicelles loaded with doxorubicin and superparamagnetic iron oxide. Eur J Radiol 80:699–705

    Google Scholar 

  • Lin JP, Zhu JQ, Chen T, Lin SL, Cai CH, Zhang LS, Zhuang Y, Wang XS (2009) Drug releasing behavior of hybrid micelles containing polypeptide triblock copolymer. Biomaterials 30:108–117

    Article  CAS  Google Scholar 

  • Liu F, Park JY, Zhang Y, Conwell C, Liu Y, Bathula SR, Huang L (2010) Targeted cancer therapy with novel high drug-loading nanocrystals. J Pharm Sci 99:3542–3551

    Article  CAS  Google Scholar 

  • Liu Y, Sun J, Cao W, Yang J, Lian H, Li X, Sun Y, Wang Y, Wang S, He Z (2011) Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery. Int J Pharm 421:160–169

    Article  CAS  Google Scholar 

  • Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284. http://dx.doi.org/10.1016/S0168-3659(99)00248-5

    Google Scholar 

  • Matsumura Y (2010) Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev 63:184–192

    Article  Google Scholar 

  • Matsumura Y, Kataoka K (2009) Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. Cancer Sci 100:572–579

    Article  CAS  Google Scholar 

  • Mikhail AS, Allen C (2009) Block copolymer micelles for delivery of cancer therapy: transport at the whole body, tissue and cellular levels. J Control Release 138:214-223. http://dx.doi.org/10.1016/j.jconrel.2009.04.010

  • Minko T (2012) Receptor mediated delivery systems for cancer therapeutics. Fundam Appl Contr Release Drug Deliv 4:329–355

    Article  Google Scholar 

  • Mishra B, Patel BB, Tiwari S (2010) Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomed Nanotechnol Biol Med 6:9-24. http://dx.doi.org/10.1016/j.nano.2009.04.008

  • Miyata K, Christie RJ, Kataoka K (2010) Polymeric micelles for nano-scale drug delivery. React Funct Polym. doi:10.1016/j.reactfunctpolym.2010.10.009

    Google Scholar 

  • Mudshinge SR, Deore AB, Patil S, Bhalgat CM (2011) Nanoparticles: emerging carriers for drug delivery. Saudi Pharm J. doi:10.1016/j.jsps.2011.04.001

    Google Scholar 

  • Nakayama M, Okano T (2011) Multi-targeting cancer chemotherapy using temperature-responsive drug carrier systems. React Funct Polym. doi:10.1016/j.reactfunctpolym.2010.08.006

    Google Scholar 

  • Parveen S, Misra R, Sahoo SK (2011) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomed Nanotechnol Biol Med 8:147–166. http://dx.doi.org/10.1016/j.nano.2011.05.016

  • Pasut G, Veronese FM (2009) PEG conjugates in clinical development or use as anticancer agents: An overview. Adv Drug Deliv Rev 61:1177–1188. http://dx.doi.org/10.1016/j.addr.2009.02.010

  • Patravale V, Date AA, Kulkarni R (2004) Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol 56:827–840

    Article  CAS  Google Scholar 

  • Peer D, Karp JM, Hong S, FaroKHzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. doi:10.1038/nnano.2007.387

    Google Scholar 

  • Polyak K, Haviv I, Campbell IG (2009) Co-evolution of tumor cells and their microenvironment. Trends Genet. doi:10.1016/j.tig.2008.10.012

    Google Scholar 

  • Ponta A, Bae Y (2010) Peg-poly (amino acid) block copolymer micelles for tunable drug release. Pharm Res 27:2330–2342

    Article  CAS  Google Scholar 

  • Qian F, Huang J, Hussain MA (2010) Drug-polymer solubility and miscibility: stability consideration and practical challenges in amorphous solid dispersion development. J Pharm Sci 99:2941–2947

    CAS  Google Scholar 

  • Rapoport N (2007) Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci 32:962–990

    Article  CAS  Google Scholar 

  • Rapoport NY, Kennedy AM, Shea JE, Scaife CL, Nam KH (2009) Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles. J Control Release 138:268–276

    Article  CAS  Google Scholar 

  • Ren TB, Feng Y, Zhang ZH, Li L, Li YY (2011) Shell-sheddable micelles based on star-shaped poly (ε-caprolactone)-SS-poly (ethyl glycol) copolymer for intracellular drug release. Soft Matter 7:2329–2331

    Article  CAS  Google Scholar 

  • Seigneuric R, Markey L, Nuyten SA, Dubernet DC, Evelo TAC, Finot E, Garrido C (2010) From nanotechnology to nanomedicine: applications to cancer research. Curr Mol Med 10:640–652

    Article  CAS  Google Scholar 

  • Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M (2010) Multi-stage delivery nano-particle systems for therapeutic applications. BBA-Gen subjects 1810:317–329. http://dx.doi.org/10.1016/j.bbagen.2010.05.004

  • Simnick AJ, Amiram M, Liu W, Hanna G, Dewhirst MW, Kontos CD, Chilkoti A (2011) In vivo tumor targeting by a NGR decorated micelle of a recombinant diblock copolypeptide. J Control Release 155:144–151

    Article  CAS  Google Scholar 

  • Song Z, Feng R, Sun M, Guo C, Gao Y, Li L, Zhai G (2011) Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: preparation, pharmacokinetics and distribution in vivo. J Colloid Interface Sci 354:116–123

    Article  CAS  Google Scholar 

  • Soppimath KS, Tan DCW, Yang YY (2005) pH-triggered thermally responsive polymer core-shell nanoparticles for drug delivery. Adv Mater 17:318–323

    Article  CAS  Google Scholar 

  • Stohrer M, Boucher Y, Stangassinger M, Jain RK (2000) Oncotic pressure in solid tumors is elevated. Cancer Res 60:4251–4255

    CAS  Google Scholar 

  • Strehlitz B, Reinemann C, Linkorn S, Stoltenburg R (2011) Aptamers for pharmaceuticals and their application in environmental analytics. Bioanal Rev 4:1–30. doi:10.1007/s12566-011-0026-1

    Article  Google Scholar 

  • Talekar M, Kendall J, Denny W, Garg S (2011) Targeting of nanoparticles in cancer: drug delivery and diagnostics. Anticancer Drug 22:949–962. doi:10.1097/CAD.0b013e32834a4554

    Article  CAS  Google Scholar 

  • Talelli M, Hennink WE (2011) Thermosensitive polymeric micelles for targeted drug delivery. Nanomedicine. doi:10.2217/nnm.11.91

    Google Scholar 

  • Talelli M, Rijcken CJF, Oliveira S, der Meel R, Henegouwen PMP, Lammers T, van Nostrum CF, Storm G, Hennink WE (2011) Nanobody-shell functionalized thermosensitive core-crosslinked polymeric micelles for active drug targeting. J Control Release 151:183–192

    Article  CAS  Google Scholar 

  • Tanaka T, Decuzzi P, Cristofanilli M, Sakamoto JH, Tasciotti E, Robertson FM, Ferrari M (2009) Nanotechnology for breast cancer therapy. Biomed Microdevices 11:49–63

    Article  CAS  Google Scholar 

  • Torchilin VP (2010) Antinuclear antibodies with nucleosome-restricted specificity for targeted delivery of chemotherapeutic agents. Ther Deliv 2:257–272. doi:10.4155/TDE.10.30

    Article  Google Scholar 

  • Wang X, Yang L, Chen ZG, Shin DM (2008) Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin 58:97–110

    Article  Google Scholar 

  • Wang L, Zeng R, Li C, Qiao RZ (2009) Self-assembled polypeptide-block-poly(vinylpyrrolidone) as prospective drug-delivery systems. Colloid Surf B 74:284–292

    Article  CAS  Google Scholar 

  • Wang X, Wang B, Zhang Q (2011) Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13. Acta Pharm Sin B 1:80–83. http://dx.doi.org/10.1016/j.apsb.2011.06.002

  • Wei H, Cheng SX, Zhang XZ, Zhuo RX (2009) Thermo-sensitive polymeric micelles based on poly (<i>N</i>-isopropylacrylamide) as drug carriers. Prog Polym Sci 34:893–910

    Article  CAS  Google Scholar 

  • Xiao L, Xiong X, Sun X, Zhu Y, Yang H, Chen H, Gan L, Xu H, Yang X (2011) Role of cellular uptake in the reversal of multidrug resistance by PEG-b-PLA polymeric micelles. Biomaterials 32:5148–5157

    Article  CAS  Google Scholar 

  • Xiao Z, Frieder J, Teply BA, Farokhzad OC (2012) Aptamer conjugates: emerging delivery platforms for targeted cancer therapy. Drug Deliv Oncol 1263–1281. doi:10.1002/9783527634057.ch39

  • Xie J, Lee S, Chen X (2010) Nanoparticle-based theranostic agents. Adv Drug Deliv Rev 62:1064–1079

    Article  CAS  Google Scholar 

  • Yang M, Wang P, Huang CY, Ku MS, Liu H, Gogos C (2010) Solid dispersion of acetaminophen and poly (ethylene oxide) prepared by hot-melt mixing. Int J Pharm 395:53–61

    Article  CAS  Google Scholar 

  • Yang K, Yang CH, Li Z (2011) Synthesis and Characterization of PVA/MMT Porous Nanocomposite Prepared by Directional Freeze-Drying Method. Adv Material Res 197:253–260

    Article  Google Scholar 

  • Yin H, Bae YH (2009) Physicochemical aspects of doxorubicin-loaded pH-sensitive polymeric micelle formulations from a mixture of poly (l-histidine)-b-poly (l-lactide)-b-poly (ethylene glycol). Eur J Pharm Biopharm 71:223–230

    Article  CAS  Google Scholar 

  • Yokoyama M (2010) Polymeric micelles as a new drug carrier system and their required considerations for clinical trials. Expert Opin Drug Deliv 7:145–158

    Article  CAS  Google Scholar 

  • Yokoyama M (2011) Clinical applications of polymeric micelle carrier systems in chemotherapy and image diagnosis of solid tumors. J Exp Clin Med 3:151–158. http://dx.doi.org/10.1016/j.jecm. 2011.06.002

    Google Scholar 

  • Yokoyama M, Kwon GS, Okano T, Sakurai Y, Seto T, Kataoka K (1992) Preparation of micelle-forming polymer drug conjugates. Bioconjug Chem 3:295–301

    Article  CAS  Google Scholar 

  • Yoshitomi T, Hirayama A, Nagasaki Y (2011) The ROS scavenging and renal protective effects of pH-responsive nitroxide radical-containing nanoparticles. Biomaterials 32:8021–8028

    Article  CAS  Google Scholar 

  • You JO, Almeda D, Ye GJC, Auguste DT (2010) Bioresponsive matrices in drug delivery. J Biol Eng 4:15. doi:10.1186/1754-1611-4-15

    Article  CAS  Google Scholar 

  • Zaman NT, Yang YY, Ying JY (2010) Stimuli-responsive polymers for the targeted delivery of paclitaxel to hepatocytes. Nano Today 5:9–14

    Article  CAS  Google Scholar 

  • Zhan C, Gu B, Xie C, Li J, Liu Y, Lu W (2010) Cyclic RGD conjugated poly (ethylene glycol)-co-poly (lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release 143:136–142

    Article  CAS  Google Scholar 

  • Zhang L, Zhu S, Qian L, Pei Y, Qiu Y, Jiang Y (2011) RGD-modified PEG-PAMAM-DOX Conjugates: in vitro and In vivo Studies for Glioma. Eur J Pharm Biopharm 79:232–240

    Article  CAS  Google Scholar 

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  1. Shandong Provincial Key Laboratory of Microbial Engineering, Shandong Polytechnic University, Jinan, Shandong, People’s Republic of China

    Hui Ding, Xiaojun Wang, Song Zhang & Xinli Liu

  2. Food and Bioengineering Institute, Shandong Polytechnic University, Daxue Road, Western University Science Park, Jinan, Shandong, People’s Republic of China

    Xinli Liu

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  1. Hui Ding
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Correspondence to Xinli Liu.

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Hui Ding and Xiaojun Wang contributed equally to this work.

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Ding, H., Wang, X., Zhang, S. et al. Applications of polymeric micelles with tumor targeted in chemotherapy. J Nanopart Res 14, 1254 (2012). https://doi.org/10.1007/s11051-012-1254-1

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