Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy

Abstract

Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis.

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References

  1. 1.

    Baudino TA. Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol. Bentham Science Publishers. 2015;12:3–20.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Mohammadi M, Ramezani M, Abnous K, Alibolandi M. Biocompatible polymersomes-based cancer theranostics: towards multifunctional nanomedicine. Int J Pharm. Elsevier. 2017;519:287–303.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Yin H, Kang S-W, Bae YH. Polymersome formation from AB2 type 3-miktoarm star copolymers. Macromolecules. ACS Publications. 2009;42:7456–64.

    CAS  Article  Google Scholar 

  4. 4.

    Hu Y, Qiu L. Polymersomes: preparation and characterization. Pharm Nanotechnol. Springer. 2019:247–65.

  5. 5.

    Yoo J, Park C, Yi G, Lee D, Koo H. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers (Basel). Multidisciplinary Digital Publishing Institute. 2019;11:640.

    CAS  Article  Google Scholar 

  6. 6.

    Alibolandi M, Shahriari M, Ramezani M. Smart polymersomes as intelligent nanomedicines in cancer treatment. Polym Nanoparticles as a Promis Tool Anti-cancer Ther. Elsevier. 2019:343–71.

  7. 7.

    Pegoraro C, Cecchin D, Gracia LS, Warren N, Madsen J, Armes SP, et al. Enhanced drug delivery to melanoma cells using PMPC-PDPA polymersomes. Cancer Lett. 2013;334:328–37.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Shahriari M, Taghdisi SM, Abnous K, Ramezani M, Alibolandi M. Synthesis of hyaluronic acid-based polymersomes for doxorubicin delivery to metastatic breast cancer. Int J Pharm Elsevier. 2019;118835.

  9. 9.

    Wang X, Yao C, Zhang G, Liu S. Regulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition. Nat Commun Nature Publishing Group. 2020;11:1–13.

    CAS  Article  Google Scholar 

  10. 10.

    Qin H, Jiang Y, Zhang J, Deng C, Zhong Z. Oncoprotein inhibitor rigosertib loaded in ApoE-targeted smart polymersomes reveals high safety and potency against human glioblastoma in mice. Mol Pharm. 2019;16:3711–9.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Ge X, Zhang Q, Cai Y, Duan S, Chen S, Lv N, et al. PEG–PCL–DEX polymersome–protamine vector as an efficient gene delivery system via PEG-guided self-assembly. Nanomedicine. Future Medicine. 2014;9:1193–207.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Kim HO, Lim JW, Choi J, Lee H, Son HY, Kim J, et al. Anchored protease-activatable polymersomes for molecular diagnostics of metastatic cancer cells. J Mater Chem B. 2017;5:9571–8.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Lansalot M, Rieger J, D’Agosto F. Polymerization-induced self-assembly: the contribution of controlled radical polymerization to the formation of self-stabilized polymer particles of various morphologies. Macromol self-assembly. Wiley Online Library. 2016:33–82.

  14. 14.

    Matyjaszewski K, Spanswick J. Controlled/living radical polymerization. Mater Today. Elsevier. 2005;8:26–33.

    CAS  Article  Google Scholar 

  15. 15.

    Balasubramanian V, Herranz-Blanco B, Almeida PV, Hirvonen J, Santos HA. Multifaceted polymersome platforms: spanning from self-assembly to drug delivery and protocells. Prog Polym Sci. Elsevier. 2016;60:51–85.

    CAS  Article  Google Scholar 

  16. 16.

    Rideau E, Dimova R, Schwille P, Wurm FR, Landfester K. Liposomes and polymersomes: a comparative review towards cell mimicking. Chem Soc Rev Royal Society of Chemistry. 2018;47:8572–610.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Meng F, Zhong Z, Feijen J. Stimuli-responsive polymersomes for programmed drug delivery. Biomacromolecules. ACS Publications. 2009;10:197–209.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Barros SM, Whitaker SK, Sukthankar P, Avila LA, Gudlur S, Warner M, et al. A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules. Arch Biochem Biophys Elsevier. 2016;596:22–42.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  19. 19.

    Yin H, Kang HC, Huh KM, Bae YH. Biocompatible, pH-sensitive AB 2 miktoarm polymer-based polymersomes: preparation, characterization, and acidic pH-activated nanostructural transformation. J Mater Chem Royal Society of Chemistry. 2012;22:19168–78.

    CAS  Article  Google Scholar 

  20. 20.

    Men Y, Peng F, Tu Y, van Hest JCM, Wilson DA. Methods for production of uniform small-sized polymersome with rigid membrane. Polym Chem. Royal Society of Chemistry. 2016;7:3977–82.

    CAS  Google Scholar 

  21. 21.

    Krishnamoorthy B, Karanam V, Chellan VR, Siram K, Natarajan TS, Gregory M. Polymersomes as an effective drug delivery system for glioma–a review. J Drug Target. Taylor & Francis. 2014;22:469–77.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kricheldorf HR. Polypeptides and 100 years of chemistry of α-amino acid N-carboxyanhydrides. Angew Chem Int Ed. Wiley Online Library. 2006;45:5752–84.

    CAS  Article  Google Scholar 

  23. 23.

    Vlakh E, Ananyan A, Zashikhina N, Hubina A, Pogodaev A, Volokitina M, et al. Preparation, characterization, and biological evaluation of poly (glutamic acid)-b-polyphenylalanine polymersomes. Polymers (Basel). Multidisciplinary Digital Publishing Institute. 2016;8:212.

    Article  Google Scholar 

  24. 24.

    Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. Elsevier. 2016;99:28–51.

    CAS  Article  Google Scholar 

  25. 25.

    Thambi T, Lee DS. Stimuli-responsive polymersomes for cancer therapy. Stimuli Responsive Polym Nanocarriers Drug Deliv Appl. Elsevier. 2019:413–38.

  26. 26.

    Zhang X, Zhang P. Polymersomes in nanomedicine-A review. Curr Nanosci. Bentham Science Publishers. 2017;13:124–9.

    CAS  Article  Google Scholar 

  27. 27.

    Matoori S, Leroux J-C. Twenty-five years of polymersomes: lost in translation? Mater Horizons. Royal Society of Chemistry. 2020.

  28. 28.

    Lee JS, Feijen J. Polymersomes for drug delivery: design, formation and characterization. J Control Release Elsevier. 2012;161:473–83.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Discher DE, Ahmed F. Polymersomes. Annu Rev Biomed Eng Annual Reviews. 2006;8:323–41.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Brinkhuis RP, Rutjes FPJT, van Hest JCM. Polymeric vesicles in biomedical applications. Polym Chem Royal Society of Chemistry. 2011;2:1449–62.

    CAS  Article  Google Scholar 

  31. 31.

    Bleul R, Thiermann R, Maskos M. Techniques to control polymersome size. Macromolecules. ACS Publications. 2015;48:7396–409.

    CAS  Article  Google Scholar 

  32. 32.

    Leong J, Teo JY, Aakalu VK, Yang YY, Kong H. Engineering polymersomes for diagnostics and therapy. Adv Healthc Mater. Wiley Online Library. 2018;7:1701276.

    Article  CAS  Google Scholar 

  33. 33.

    Lee JC, Bermudez H, Discher BM, Sheehan MA, Won Y, Bates FS, et al. Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. Biotechnol Bioeng. Wiley Online Library. 2001;73:135–45.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Photos PJ, Bacakova L, Discher B, Bates FS, Discher DE. Polymer vesicles in vivo: correlations with PEG molecular weight. J Control Release. Elsevier. 2003;90:323–34.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Ahmed F, Pakunlu RI, Brannan A, Bates F, Minko T, Discher DE. Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. J Control Release. 2006;116:150–8.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Guan L, Rizzello L, Battaglia G. Polymersomes and their applications in cancer delivery and therapy. Nanomedicine. Future Medicine. 2015;10:2757–80.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Anajafi T, Mallik S. Polymersome-based drug-delivery strategies for cancer therapeutics. Ther Deliv. Future Science. 2015;6:521–34.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  38. 38.

    Matoori S, Bao Y, Schmidt A, Fischer EJ, Ochoa-Sanchez R, Tremblay M, et al. An investigation of PS-b-PEO polymersomes for the oral treatment and diagnosis of hyperammonemia. Small. Wiley Online Library. 2019;15:1902347.

    CAS  Article  Google Scholar 

  39. 39.

    Lorenceau E, Utada AS, Link DR, Cristobal G, Joanicot M, Weitz DA. Generation of polymerosomes from double-emulsions. Langmuir. ACS Publications. 2005;21:9183–6.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Allen S, Osorio O, Liu Y-G, Scott E. Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation. J Control Release. Elsevier. 2017;262:91–103.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  41. 41.

    Rijpkema SJ, Langens SGHA, van der Kolk MR, Gavriel K, Toebes BJ, Wilson DA. Modular approach to the functionalization of polymersomes. Biomacromolecules. ACS Publications. 2020.

  42. 42.

    Meghani NM, Amin HH, Lee B-J. Mechanistic applications of click chemistry for pharmaceutical drug discovery and drug delivery. Drug Discov Today. Elsevier. 2017;22:1604–19.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Rasheed T, Bilal M, Abu-Thabit NY, Iqbal HMN. The smart chemistry of stimuli-responsive polymeric carriers for target drug delivery applications. Stimuli Responsive Polym Nanocarriers Drug Deliv Appl. 2018;1. Elsevier:61–99.

    Article  Google Scholar 

  44. 44.

    Itel F, Chami M, Najer A, Lörcher S, Wu D, Dinu IA, et al. Molecular organization and dynamics in polymersome membranes: a lateral diffusion study. Macromolecules. ACS Publications. 2014;47:7588–96.

    CAS  Article  Google Scholar 

  45. 45.

    Lee K, David AE, Zhang J, Shin MC, Yang VC. Enhanced accumulation of theranostic nanoparticles in brain tumor by external magnetic field mediated in situ clustering of magnetic nanoparticles. J Ind Eng Chem. 2017;54:389–97.

    CAS  Article  Google Scholar 

  46. 46.

    Gustafson HH, Holt-Casper D, Grainger DW, Ghandehari H. Nanoparticle uptake: the phagocyte problem. Nano Today. Elsevier. 2015;10:487–510.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  47. 47.

    Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. ACS Publications. 2008;5:505–15.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  48. 48.

    Lu W-L, Qi X-R, Zhang Q, Li R-Y, Wang G-L, Zhang R-J, et al. A pegylated liposomal platform: pharmacokinetics, pharmacodynamics, and toxicity in mice using doxorubicin as a model drug. J Pharmacol Sci. The Japanese Pharmacological Society. 2004;95:381–9.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    de Kruijff RM, Raavé R, Kip A, Molkenboer-Kuenen J, Roobol SJ, Essers J, et al. Elucidating the influence of tumor presence on the polymersome circulation time in mice. Pharmaceutics. Multidisciplinary Digital Publishing Institute. 2019;11:241.

    PubMed Central  Article  CAS  Google Scholar 

  50. 50.

    Choucair A, Lim Soo P, Eisenberg A. Active loading and tunable release of doxorubicin from block copolymer vesicles. Langmuir. ACS Publications. 2005;21:9308–13.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Ahmed F, Pakunlu RI, Srinivas G, Brannan A, Bates F, Klein ML, et al. Shrinkage of a rapidly growing tumor by drug-loaded polymersomes: pH-triggered release through copolymer degradation. Mol Pharm. ACS Publications. 2006;3:340–50.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. Dove Press. 2015;10:975.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  53. 53.

    Chandrawati R, Caruso F. Biomimetic liposome-and polymersome-based multicompartmentalized assemblies. Langmuir. ACS Publications. 2012;28:13798–807.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Schulz M, Binder WH. Mixed hybrid lipid/polymer vesicles as a novel membrane platform. Macromol Rapid Commun. Wiley Online Library. 2015;36:2031–41.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Lee JH, Yeo Y. Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci. Elsevier. 2015;125:75–84.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Zhao Y, Li X, Zhao X, Yang Y, Li H, Zhou X, et al. Asymmetrical polymer vesicles for drug delivery and other applications. Front Pharmacol. Frontiers. 2017;8:374.

    PubMed Central  PubMed  Google Scholar 

  57. 57.

    Cho HK, Cheong IW, Lee JM, Kim JH. Polymeric nanoparticles, micelles and polymersomes from amphiphilic block copolymer. Korean J Chem Eng. Springer. 2010;27:731–40.

    CAS  Article  Google Scholar 

  58. 58.

    Yao C, Wang X, Hu J, Liu S. Cooperative modulation of bilayer permeability and microstructures of polymersomes. Acta Polym Sin. 2019;6:553–66.

    Google Scholar 

  59. 59.

    Mumtaz Virk M, Reimhult E. Phospholipase A2-induced degradation and release from lipid-containing polymersomes. Langmuir. ACS Publications. 2018;34:395–405.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Alibolandi M, Abnous K, Mohammadi M, Hadizadeh F, Sadeghi F, Taghavi S, et al. Extensive preclinical investigation of polymersomal formulation of doxorubicin versus doxil-mimic formulation. J Control Release. 2017;264:228–36.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Ayen WY, Kumar N. In vivo evaluation of doxorubicin-loaded (PEG) 3-PLA nanopolymersomes (PolyDoxSome) using DMBA-induced mammary carcinoma rat model and comparison with marketed LipoDox™. Pharm Res. Springer. 2012;29:2522–33.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Zou Y, Meng F, Deng C, Zhong Z. Robust, tumor-homing and redox-sensitive polymersomal doxorubicin: a superior alternative to doxil and caelyx? J Control Release. 2016;239:149–58.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Youssef SF, Elnaggar YSR, Abdallah OY. Elaboration of polymersomes versus conventional liposomes for improving oral bioavailability of the anticancer flutamide. Nanomedicine. Future Medicine. 2018;13:3025–36.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Zou Y, Xia Y, Meng F, Zhang J, Zhong Z. GE11-directed functional polymersomal doxorubicin as an advanced alternative to clinical liposomal formulation for ovarian cancer treatment. Mol Pharm. 2018;15:3664–71.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Hu X, Zhang Y, Xie Z, Jing X, Bellotti A, Gu Z. Stimuli-responsive polymersomes for biomedical applications. Biomacromolecules. ACS Publications. 2017;18:649–73.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Che H, van Hest JCM. Stimuli-responsive polymersomes and nanoreactors. J Mater Chem B Royal Society of Chemistry. 2016;4:4632–47.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Puglisi A, Bayir E, Timur S, Yagci Y. pH-Responsive polymersome microparticles as smart cyclodextrin-releasing agents. Biomacromolecules. ACS Publications. 2019;20:4001–7.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Li Y, Liu G, Wang X, Hu J, Liu S. Enzyme-responsive polymeric vesicles for bacterial-strain-selective delivery of antimicrobial agents. Angew Chem Int Ed. Wiley Online Library. 2016;55:1760–4.

    CAS  Article  Google Scholar 

  69. 69.

    Sun Z, Liu G, Hu J, Liu S. Photo-and reduction-responsive polymersomes for programmed release of small and macromolecular payloads. Biomacromolecules. ACS Publications. 2018;19:2071–81.

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Zhou J, Tang Q, Zhong J, Lei Z, Luo H, Tong Z, et al. Construction of glucose and H 2 O 2 dual stimuli-responsive polymeric vesicles and their application in controlled drug delivery. J Mater Sci Springer. 2018;53:14063–74.

    CAS  Article  Google Scholar 

  71. 71.

    Yan Q, Yuan J, Cai Z, Xin Y, Kang Y, Yin Y. Voltage-responsive vesicles based on orthogonal assembly of two homopolymers. J Am Chem Soc ACS Publications. 2010;132:9268–70.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Oliveira H, Pérez-Andrés E, Thevenot J, Sandre O, Berra E, Lecommandoux S. Magnetic field triggered drug release from polymersomes for cancer therapeutics. J Control Release. 2013;169:165–70.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int. Springer. 2013;13:89.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  74. 74.

    Meng F, Hiemstra C, Engbers GHM, Feijen J. Biodegradable polymersomes. Macromolecules ACS Publications. 2003;36:3004–6.

    CAS  Article  Google Scholar 

  75. 75.

    Chen W, Meng F, Cheng R, Zhong Z. pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: a comparative study with micelles. J Control Release Elsevier. 2010;142:40–6.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Qiao Z-Y, Cheng J, Ji R, Du F-S, Liang D-H, Ji S-P, et al. Biocompatible acid-labile polymersomes from PEO-b-PVA derived amphiphilic block copolymers. RSC Adv Royal Society of Chemistry. 2013;3:24345–53.

    CAS  Article  Google Scholar 

  77. 77.

    Brinkhuis RP, Visser TR, Rutjes FPJT, van Hest JCM. Shedding the hydrophilic mantle of polymersomes. Polym Chem Royal Society of Chemistry. 2011;2:550–2.

    CAS  Article  Google Scholar 

  78. 78.

    Yoshida T, Lai TC, Kwon GS, Sako K. pH-and ion-sensitive polymers for drug delivery. Expert Opin Drug Deliv Taylor & Francis. 2013;10:1497–513.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  79. 79.

    Lodge TP, Rasdal A, Li Z, Hillmyer MA. Simultaneous, segregated storage of two agents in a multicompartment micelle. J Am Chem Soc ACS Publications. 2005;127:17608–9.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Du J, Tang Y, Lewis AL, Armes SP. pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer. J Am Chem Soc ACS Publications. 2005;127:17982–3.

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Massignani M, Canton I, Sun T, Hearnden V, MacNeil S, Blanazs A, et al. Enhanced fluorescence imaging of live cells by effective cytosolic delivery of probes. PLoS One Public Library of Science. 2010;5.

  82. 82.

    Min KH, Kim J-H, Bae SM, Shin H, Kim MS, Park S, et al. Tumoral acidic pH-responsive MPEG-poly (β-amino ester) polymeric micelles for cancer targeting therapy. J Control Release Elsevier. 2010;144:259–66.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Kim DH, Seo YK, Thambi T, Moon GJ, Son JP, Li G, et al. Enhancing neurogenesis and angiogenesis with target delivery of stromal cell derived factor-1α using a dual ionic pH-sensitive copolymer. Biomaterials Elsevier. 2015;61:115–25.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Caon T, Porto LC, Granada A, Tagliari MP, Silva MAS, Simões CMO, et al. Chitosan-decorated polystyrene-b-poly (acrylic acid) polymersomes as novel carriers for topical delivery of finasteride. Eur J Pharm Sci Elsevier. 2014;52:165–72.

    CAS  Article  PubMed  Google Scholar 

  85. 85.

    Bellomo EG, Wyrsta MD, Pakstis L, Pochan DJ, Deming TJ. Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nat Mater. Nature Publishing Group. 2004;3:244.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Hashimoto Y, Tanaka M, Kishimoto H, Shiozawa H, Hasegawa K, Matsuyama K, et al. Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine. J Pharm Pharmacol. Wiley Online Library. 2002;54:1323–8.

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    Onaca O, Enea R, Hughes DW, Meier W. Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery. Macromol Biosci. Wiley Online Library. 2009;9:129–39.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Gandhi A, Paul A, Sen SO, Sen KK. Studies on thermoresponsive polymers: phase behaviour, drug delivery and biomedical applications. Asian J Pharm Sci. Elsevier. 2015;10:99–107.

    Article  Google Scholar 

  89. 89.

    Pfleiderer SOR, Marx C, Camara O, Gajda M, Kaiser WA. Ultrasound-guided, percutaneous cryotherapy of small (≤ 15 mm) breast cancers. Investig Radiol. LWW. 2005;40:472–7.

    Article  Google Scholar 

  90. 90.

    Qin S, Geng Y, Discher DE, Yang S. Temperature-controlled assembly and release from polymer vesicles of poly (ethylene oxide)-block-poly (N-isopropylacrylamide). Adv Mater. Wiley Online Library. 2006;18:2905–9.

    CAS  Article  Google Scholar 

  91. 91.

    Cheng R, Meng F, Ma S, Xu H, Liu H, Jing X, et al. Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery. J Mater Chem. Royal Society of Chemistry. 2011;21:19013–20.

    CAS  Article  Google Scholar 

  92. 92.

    Kozlovskaya V, Liu F, Yang Y, Ingle K, Qian S, Halade GV, et al. Temperature-responsive polymersomes of poly (3-methyl-N-vinylcaprolactam)-block-poly (N-vinylpyrrolidone) to decrease doxorubicin-induced cardiotoxicity. Biomacromolecules. ACS Publications. 2019;20:3989–4000.

    CAS  Article  PubMed  Google Scholar 

  93. 93.

    Tan J, Deng Z, Liu G, Hu J, Liu S. Anti-inflammatory polymersomes of redox-responsive polyprodrug amphiphiles with inflammation-triggered indomethacin release characteristics. Biomaterials. Elsevier. 2018;178:608–19.

    CAS  Article  PubMed  Google Scholar 

  94. 94.

    de Oliveira MF, Amoêdo ND, Rumjanek FD. Energy and redox homeostasis in tumor cells. Int J Cell Biol. Hindawi. 2012;2012.

  95. 95.

    Kumar A, Lale SV, Mahajan S, Choudhary V, Koul V. ROP and ATRP fabricated dual targeted redox sensitive polymersomes based on pPEGMA-PCL-ss-PCL-pPEGMA triblock copolymers for breast cancer therapeutics. ACS Appl Mater Interfaces. 2015;7:9211–27.

    CAS  Article  PubMed  Google Scholar 

  96. 96.

    Ren T, Wu W, Jia M, Dong H, Li Y, Ou Z. Reduction-cleavable polymeric vesicles with efficient glutathione-mediated drug release behavior for reversing drug resistance. ACS Appl Mater Interfaces ACS Publications. 2013;5:10721–30.

    CAS  Article  PubMed  Google Scholar 

  97. 97.

    Sun H, Meng F, Cheng R, Deng C, Zhong Z. Reduction and pH dual-bioresponsive crosslinked polymersomes for efficient intracellular delivery of proteins and potent induction of cancer cell apoptosis. Acta Biomater. 2014;10:2159–68.

    CAS  Article  PubMed  Google Scholar 

  98. 98.

    Li J, Li Y, Wang Y, Ke W, Chen W, Wang W, et al. Polymer prodrug-based nanoreactors activated by tumor acidity for orchestrated oxidation/chemotherapy. Nano Lett ACS Publications. 2017;17:6983–90.

    CAS  Article  PubMed  Google Scholar 

  99. 99.

    Sanson C, Diou O, Thévenot J, Ibarboure E, Soum A, Brûlet A, et al. Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy. ACS Nano. 2011;5:1122–40.

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    García MC. Stimuli-responsive polymersomes for drug delivery applications. Stimuli Responsive Polym Nanocarriers Drug Deliv Appl. Elsevier. 2019:345–92.

  101. 101.

    Yamamoto S, Yamada T, Kubo G, Sakurai K, Yamaguchi K, Nakanishi J. Preparation of a series of photoresponsive polymersomes bearing photocleavable a 2-nitrobenzyl group at the hydrophobic/hydrophilic interfaces and their payload releasing behaviors. Polymers (Basel). Multidisciplinary Digital Publishing Institute. 2019;11:1254.

    CAS  Article  Google Scholar 

  102. 102.

    Lee JS, Groothuis T, Cusan C, Mink D, Feijen J. Lysosomally cleavable peptide-containing polymersomes modified with anti-EGFR antibody for systemic cancer chemotherapy. Biomaterials Elsevier. 2011;32:9144–53.

    CAS  Article  PubMed  Google Scholar 

  103. 103.

    Iatridi Z, Angelopoulou A, Voulgari E, Avgoustakis K, Tsitsilianis C. Star-Graft quarterpolymer-based polymersomes as nanocarriers for co-delivery of hydrophilic/hydrophobic chemotherapeutic agents. ACS Omega. 2018;3:11896–908.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  104. 104.

    Chen W, Du J. Ultrasound and pH dually responsive polymer vesicles for anticancer drug delivery. Sci Rep. Nature Publishing Group. 2013;3:2162.

    PubMed Central  Article  PubMed  Google Scholar 

  105. 105.

    Lu F, Pang Z, Zhao J, Jin K, Li H, Pang Q, et al. Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats. Int J Nanomedicine. 2017;12:2117–27.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  106. 106.

    Figueiredo P, Balasubramanian V, Shahbazi MA, Correia A, Wu D, Palivan CG, et al. Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells. Int J Pharm. 2016;511:794–803.

    CAS  Article  PubMed  Google Scholar 

  107. 107.

    Chen YC, Chiang CF, Chen LF, Liang PC, Hsieh WY, Lin WL. Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system. Biomaterials. 2014;35:4066–81.

    CAS  Article  PubMed  Google Scholar 

  108. 108.

    Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S, et al. Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem. 2011;22:1171–80.

    CAS  Article  PubMed  Google Scholar 

  109. 109.

    Alibolandi M, Abnous K, Sadeghi F, Hosseinkhani H, Ramezani M, Hadizadeh F. Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: in vitro and in vivo evaluation. Int J Pharm. 2016;500:162–78.

    CAS  Article  PubMed  Google Scholar 

  110. 110.

    Cao J, Wei Y, Zhang Y, Wang G, Ji X, Zhong Z. Iodine-rich polymersomes enable versatile SPECT/CT imaging and potent radioisotope therapy for tumor in vivo. ACS Appl Mater Interfaces. 2019;11:18953–9.

    CAS  Article  PubMed  Google Scholar 

  111. 111.

    Bessone MID, Simón-Gracia L, Scodeller P, de los Angeles Ramirez M, Huvelle MAL, Soler-Illia GJAA, et al. iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity. J Nanobiotechnol. BioMed Central. 2019;17:1–14.

    Article  Google Scholar 

  112. 112.

    Lale SV, Kumar A, Prasad S, Bharti AC, Koul V. Folic acid and trastuzumab functionalized redox responsive polymersomes for intracellular doxorubicin delivery in breast cancer. Biomacromolecules. 2015;16:1736–52.

    CAS  Article  PubMed  Google Scholar 

  113. 113.

    Zhang Y, Wu K, Sun H, Zhang J, Yuan J, Zhong Z. Hyaluronic acid-shelled disulfide-cross-linked nanopolymersomes for ultrahigh-efficiency reactive encapsulation and CD44-targeted delivery of mertansine toxin. ACS Appl Mater Interfaces. 2018;10:1597–604.

    CAS  Article  PubMed  Google Scholar 

  114. 114.

    Xu J, Zhao Q, Jin Y, Qiu L. High loading of hydrophilic/hydrophobic doxorubicin into polyphosphazene polymersome for breast cancer therapy. Nanomedicine Nanotechnology, Biol Med. 2014;10:349–58.

    CAS  Article  PubMed  Google Scholar 

  115. 115.

    Yang W, Wei Y, Yang L, Zhang J, Zhong Z, Storm G, et al. Granzyme B-loaded, cell-selective penetrating and reduction-responsive polymersomes effectively inhibit progression of orthotopic human lung tumor in vivo. J Control Release. 2018;290:141–9.

    CAS  Article  PubMed  Google Scholar 

  116. 116.

    Yang W, Yang L, Xia Y, Cheng L, Zhang J, Meng F, et al. Lung cancer specific and reduction-responsive chimaeric polymersomes for highly efficient loading of pemetrexed and targeted suppression of lung tumor in vivo. Acta Biomater. 2018;70:177–85.

    CAS  Article  PubMed  Google Scholar 

  117. 117.

    Zou Y, Wei J, Xia Y, Meng F, Yuan J, Zhong Z. Targeted chemotherapy for subcutaneous and orthotopic non-small cell lung tumors with cyclic RGD-functionalized and disulfide-crosslinked polymersomal doxorubicin. Signal Transduct Target Ther. 2018;3:32.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  118. 118.

    Yang W, Zou Y, Meng F, Zhang J, Cheng R, Deng C, et al. Efficient and targeted suppression of human lung tumor xenografts in mice with methotrexate sodium encapsulated in all-function-in-one chimeric polymersomes. Adv Mater. 2016;28:8234–9.

    CAS  Article  PubMed  Google Scholar 

  119. 119.

    Yang W, Xia Y, Fang Y, Meng F, Zhang J, Cheng R, et al. Selective cell penetrating peptide-functionalized polymersomes mediate efficient and targeted delivery of methotrexate disodium to human lung cancer in vivo. Adv Healthc Mater. 2018;7:1701135.

    Article  CAS  Google Scholar 

  120. 120.

    Alibolandi M, Ramezani M, Abnous K, Hadizadeh F. AS1411 Aptamer-decorated biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanopolymersomes for the targeted delivery of gemcitabine to non-small cell lung cancer in vitro. J Pharm Sci. 2016;105:1741–50.

    CAS  Article  PubMed  Google Scholar 

  121. 121.

    Peng Y, Zhu X, Qiu L. Electroneutral composite polymersomes self-assembled by amphiphilic polyphosphazenes for effective miR-200c in vivo delivery to inhibit drug resistant lung cancer. Biomaterials. 2016;106:1–12.

    CAS  Article  PubMed  Google Scholar 

  122. 122.

    Karandish F, Mamnoon B, Feng L, Haldar MK, Xia L, Gange KN, et al. Nucleus-targeted, echogenic polymersomes for delivering a cancer stemness inhibitor to pancreatic cancer cells. Biomacromolecules. 2018;19:4122–32.

    CAS  Article  PubMed  Google Scholar 

  123. 123.

    Anajafi T, Yu J, Sedigh A, Haldar MK, Muhonen WW, Oberlander S, et al. Nuclear localizing peptide-conjugated, redox-sensitive polymersomes for delivering curcumin and doxorubicin to pancreatic cancer microtumors. Mol Pharm. 2017;14:1916–28.

    CAS  Article  PubMed  Google Scholar 

  124. 124.

    Anajafi T, Scott MD, You S, Yang X, Choi Y, Qian SY, et al. Acridine orange conjugated polymersomes for simultaneous nuclear delivery of gemcitabine and doxorubicin to pancreatic cancer cells. Bioconjug Chem. 2016;27:762–71.

    CAS  Article  PubMed  Google Scholar 

  125. 125.

    Kulkarni P, Haldar MK, You S, Choi Y, Mallik S. Hypoxia-responsive polymersomes for drug delivery to hypoxic pancreatic cancer cells. Biomacromolecules. 2016;17:2507–13.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  126. 126.

    Iatrou H, Dimas K, Gkikas M, Tsimblouli C, Sofianopoulou S. Polymersomes from polypeptide containing triblock co-and terpolymers for drug delivery against pancreatic cancer: asymmetry of the external hydrophilic blocks. Macromol Biosci Wiley Online Library. 2014;14:1222–38.

    CAS  Article  PubMed  Google Scholar 

  127. 127.

    Karandish F, Haldar MK, You S, Brooks AE, Brooks BD, Guo B, et al. Prostate-specific membrane antigen targeted polymersomes for delivering mocetinostat and docetaxel to prostate cancer cell spheroids. ACS Omega. 2016;1:952–62.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  128. 128.

    Li X, Yang W, Zou Y, Meng F, Deng C, Zhong Z. Efficacious delivery of protein drugs to prostate cancer cells by PSMA-targeted pH-responsive chimaeric polymersomes. J Control Release. 2015;220:704–14.

    CAS  Article  PubMed  Google Scholar 

  129. 129.

    Demirgöz D, Pangburn TO, Davis KP, Lee S, Bates FS, Kokkoli E. PR-b-targeted delivery of tumor necrosis factor-α by polymersomes for the treatment of prostate cancer. Soft Matter. 2009;5:2011–9.

    Article  CAS  Google Scholar 

  130. 130.

    Fang Y, Yang W, Cheng L, Meng F, Zhang J, Zhong Z. EGFR-targeted multifunctional polymersomal doxorubicin induces selective and potent suppression of orthotopic human liver cancer in vivo. Acta Biomater. 2017;64:323–33.

    CAS  Article  PubMed  Google Scholar 

  131. 131.

    Wei Y, Gu X, Cheng L, Meng F, Storm G, Zhong Z. Low-toxicity transferrin-guided polymersomal doxorubicin for potent chemotherapy of orthotopic hepatocellular carcinoma in vivo. Acta Biomater. 2019;92:196–204.

    CAS  Article  PubMed  Google Scholar 

  132. 132.

    Wang X, Sun H, Meng F, Cheng R, Deng C, Zhong Z. Galactose-decorated reduction-sensitive degradable chimaeric polymersomes as a multifunctional nanocarrier to efficiently chaperone apoptotic proteins into hepatoma cells. Biomacromolecules. 2013;14:2873–82.

    CAS  Article  PubMed  Google Scholar 

  133. 133.

    Alibolandi M, Rezvani R, Farzad SA, Taghdisi SM, Abnous K, Ramezani M. Tetrac-conjugated polymersomes for integrin-targeted delivery of camptothecin to colon adenocarcinoma in vitro and in vivo. Int J Pharm. 2017;532:581–94.

    CAS  Article  PubMed  Google Scholar 

  134. 134.

    Goñi-de-Cerio F, Thevenot J, Oliveira H, Pérez-Andrés E, Berra E, Masa M, et al. Cellular uptake and cytotoxic effect of epidermal growth factor receptor targeted and plitidepsin loaded co-polymeric polymersomes on colorectal cancer cell lines. J Biomed Nanotechnol. 2015;11:2034–49.

    Article  CAS  PubMed  Google Scholar 

  135. 135.

    Zhong Y, Meng F, Zhang W, Li B, van Hest JCM, Zhong Z. CD44-targeted vesicles encapsulating granzyme B as artificial killer cells for potent inhibition of human multiple myeloma in mice. J Control Release Elsevier. 2020;320:421–30.

    CAS  Article  PubMed  Google Scholar 

  136. 136.

    Gu W, An J, Meng H, Yu N, Zhong Y, Meng F, et al. CD44-Specific A6 short peptide boosts targetability and anticancer efficacy of polymersomal epirubicin to orthotopic human multiple myeloma. Adv Mater. Wiley Online Library. 2019;31:1904742.

    CAS  Article  Google Scholar 

  137. 137.

    Tang W, Fan W, Lau J, Deng L, Shen Z, Chen X. Emerging blood–brain-barrier-crossing nanotechnology for brain cancer theranostics. Chem Soc Rev. Royal Society of Chemistry. 2019.

  138. 138.

    Ulbrich K, Knobloch T, Kreuter J. Targeting the insulin receptor: nanoparticles for drug delivery across the blood–brain barrier (BBB). J Drug Target. Taylor & Francis. 2011;19:125–32.

    CAS  Article  PubMed  Google Scholar 

  139. 139.

    Abdul Razzak R, Florence GJ, Gunn-Moore FJ. Approaches to CNS drug delivery with a focus on transporter-mediated transcytosis. Int J Mol Sci. Multidisciplinary Digital Publishing Institute. 2019;20:3108.

    CAS  PubMed Central  Article  Google Scholar 

  140. 140.

    Pang Z, Feng L, Hua R, Chen J, Gao H, Pan S, et al. Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol Pharm. 2010;7:1995–2005.

    CAS  Article  PubMed  Google Scholar 

  141. 141.

    Pang Z, Fan L, Hu K, Wu B, Jiang X. Effect of lactoferrin-and transferrin-conjugated polymersomes in brain targeting: in vitro and in vivo evaluations. Acta Pharmacol Sin Nature Publishing Group. 2010;31:237–43.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  142. 142.

    Chung NS, Wasan KM. Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake. Adv Drug Deliv Rev Elsevier. 2004;56:1315–34.

    CAS  Article  PubMed  Google Scholar 

  143. 143.

    Jiang Y, Zhang J, Meng F, Zhong Z. Apolipoprotein E peptide-directed chimeric polymersomes mediate an ultrahigh-efficiency targeted protein therapy for glioblastoma. ACS Nano. 2018;12:11070–9.

    CAS  Article  PubMed  Google Scholar 

  144. 144.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  Google Scholar 

  145. 145.

    Alibolandi M, Ramezani M, Sadeghi F, Abnous K, Hadizadeh F. Epithelial cell adhesion molecule aptamer conjugated PEG-PLGA nanopolymersomes for targeted delivery of doxorubicin to human breast adenocarcinoma cell line in vitro. Int J Pharm. 2015;479:241–51.

    CAS  Article  PubMed  Google Scholar 

  146. 146.

    Pepper MS. Role of the matrix metalloproteinase and plasminogen activator–plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol. Am Heart Assoc. 2001;21:1104–17.

    CAS  Article  PubMed  Google Scholar 

  147. 147.

    Street W. Cancer facts & figures 2019. Am Cancer Soc Atlanta, GA, USA. 2019

  148. 148.

    Chiang W-H, Huang W-C, Chang C-W, Shen M-Y, Shih Z-F, Huang Y-F, et al. Functionalized polymersomes with outlayered polyelectrolyte gels for potential tumor-targeted delivery of multimodal therapies and {MR} imaging. J Control Release. 2013;168:280–8.

    CAS  Article  PubMed  Google Scholar 

  149. 149.

    Bakalova R, Lazarova D, Nikolova B, Atanasova S, Zlateva G, Zhelev Z, et al. Delivery of size-controlled long-circulating polymersomes in solid tumours, visualized by quantum dots and optical imaging {in vivo}. Biotechnol Biotechnol Equip. 2015;29:175–80.

    CAS  Article  PubMed  Google Scholar 

  150. 150.

    Zavvar T, Babaei M, Abnous K, Taghdisi SM, Nekooei S, Ramezani M, et al. Synthesis of multimodal polymersomes for targeted drug delivery and MR/fluorescence imaging in metastatic breast cancer model. Int J Pharm Elsevier. 2020;578:119091.

    CAS  Article  PubMed  Google Scholar 

  151. 151.

    Li Z, Wu L, Hu P, Han S, Zhang T, Fan H, et al. Soft nanomaterial-based targeting polymersomes for near-infrared fluorescence multispectral in vivo imaging. Nanoscale Royal Society of Chemistry. 2012;4:7097–105.

    CAS  Article  PubMed  Google Scholar 

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Sharma, A.K., Prasher, P., Aljabali, A.A. et al. Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00789-2

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Keywords

  • nanomedicine
  • nanotechnology
  • polymersomes
  • cancer therapy
  • drug delivery