Issue

Vol. 12 (2020)

Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery

https://doi.org/10.1007/s40820-020-00447-9
Yalei Miao
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Yudian Qiu
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Mengna Zhang
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Ke Yan
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Panke Zhang
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Siyu Lu
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Zhongyi Liu
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Xiaojing Shi
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
Xubo Zhao
Green Catalysis Center, College of Chemistry, and Laboratory Animal Center, Zhengzhou University, Zhengzhou 450001, People’s Republic of China

Corresponding Author: Xubo Zhao

xbz2016@zzu.edu.cn

Nano-Micro Letters, Vol. 12 (2020), Article Number: 124

Abstract

Molecular self-assembly is crucially fundamental to nature. However, the aqueous self-assembly of polymers is still a challenge. To achieve self-assembly of block copolymers [(polyacrylic acid–block–polyethylene glycol–block–polyacrylic acid (PAA68–b–PEG86–b–PAA68)] in an aqueous phase, manganese oxide (MnO2) is first generated to drive phase separation of the PAA block to form the PAA68–b–PEG86–b–PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium. The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin (DOX) loading capacity of approximately 94%. The transformation from MnO2 to Mn2+ caused by endogenous glutathione (GSH) facilitates the disassembly of PAA68–b–PEG86–b–PAA68/MnO2 to enable its drug delivery at the tumor sites. The toxicity of DOX-loaded PAA68–b–PEG86–b–PAA68/MnO2 to tumor cells has been verified in vitro and in vivo. Notably, drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to overcome the cardiotoxicity of DOX. We expect this work to encourage the potential application of polymer self-assembly.


Highlights:


1 The formation of manganese oxide induces self-assembly of block copolymers to form polymeric vesicles.
2 The polymeric vesicles possessed strong stability and high drug loading capacity.
3 The drug-loaded polymeric vesicles have been demonstrated, especially in in vivo studies, to exhibit a higher efficacy of tumor suppression without known cardiotoxicity.

Keywords

Polymer Aqueous self-assembly Vesicles Tumor microenvironment Drug delivery system
Miao, Yalei, Yudian Qiu, Mengna Zhang, Ke Yan, Panke Zhang, Siyu Lu, Zhongyi Liu, Xiaojing Shi, and Xubo Zhao. 2020. “Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery”. Nano-Micro Letters 12 (June):124. https://doi.org/10.1007/s40820-020-00447-9.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. J. Laurent, G. Blin, F. Chatelain, V. Vanneaux, A. Fuchs, J. Larghero, M. Thery, Convergence of microengineering and cellular self-organization towards functional tissue manufacturing. Nat. Biomed. Eng. 1(12), 939–956 (2017). https://doi.org/10.1038/s41551-017-0166-x
  2. O.A. Bell, G.L. Wu, J.S. Haataja, F. Brommel, N. Fey et al., Self-assembly of a functional oligo(aniline)-based amphiphile into helical conductive nanowires. J. Am. Chem. Soc. 137(45), 14288–14294 (2015). https://doi.org/10.1021/jacs.5b06892
  3. T.-Y. Dora Tang, C.R. Che Hak, A.J. Thompson, M.K. Kuimova, D.S. Williams, A.W. Perriman, S. Mann, Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. Nat. Chem. 6(6), 527–533 (2014). https://doi.org/10.1038/nchem.1921
  4. M. Karimi, P.S. Zangabad, S. Baghaee-Ravari, M. Ghazadeh, H. Mirshekari, M.R. Hamblin, Smart nanostructures for cargo delivery: uncaging and activating by light. J. Am. Chem. Soc. 139(13), 4584–4610 (2017). https://doi.org/10.1021/jacs.6b08313
  5. S.J. Newman, Note on colloidal dispersions from block copolymers. Appl. Polym. Sci. 6(21), S15–S16 (1962). https://doi.org/10.1002/app.1962.070062121
  6. S. Krause, Dilute solution properties of a styrene-methyl methacrylate block copolymer. J. Phys. Chem. 68(7), 1948–1955 (1964). https://doi.org/10.1021/j100789a046
  7. N.J. Warren, S.P. Armes, Polymerization-induced self-assembly of block copolymer nano-objects via RAFT aqueous dispersion polymerization. J. Am. Chem. Soc. 136(29), 10174–10185 (2014). https://doi.org/10.1021/ja502843f
  8. H. Cabral, K. Miyata, K. Osada, K. Kataoka, Block copolymer micelles in nanomedicine applications. Chem. Rev. 118(14), 6844–6892 (2018). https://doi.org/10.1021/acs.chemrev.8b00199
  9. B.M. Discher, Y.-Y. Won, D.S. Ege, J.C.-M. Lee, F.S. Bates, D.E. Discher, D.A. Hammer, Polymersomes: tough vesicles made from diblock copolymers. Science 284(5417), 1143–1146 (1999). https://doi.org/10.1126/science.284.5417.1143
  10. D.E. Discher, A. Eisenberg, Polymer vesicles. Science 297(5583), 967–973 (2002). https://doi.org/10.1126/science.1074972
  11. K. Ulbrich, K. Hola, V. Subr, A. Bakandritsos, J. Tucek, R. Zboril, Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies. Chem. Rev. 116(9), 5338–5431 (2016). https://doi.org/10.1021/acs.chemrev.5b00589
  12. A. Kakkar, G. Traverso, O.C. Farokhzad, R. Weissleder, R. Langer, Evolution of macromolecular complexity in drug delivery systems. Nat. Rev. Chem. 1(8), 0063 (2017). https://doi.org/10.1038/s41570-017-0063
  13. E. Blanco, H. Shen, M. Ferrari, Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33(9), 941–951 (2015). https://doi.org/10.1038/nbt.3330
  14. D.Q. Chen, G.Q. Zhang, R.M. Li, M.R. Guan, X.Y. Wang et al., Biodegradable, hydrogen peroxide, and glutathione dual responsive nanoparticles for potential programmable paclitaxel Release. J. Am. Chem. Soc. 140(24), 7373–7376 (2018). https://doi.org/10.1021/jacs.7b12025
  15. E. Ruoslahti, Tumor penetrating peptides for improved drug delivery. Adv. Drug Deliv. Rev. 110, 3–12 (2017). https://doi.org/10.1016/j.addr.2016.03.008
  16. H.Q. Zheng, Y.N. Zhang, L.F. Liu, W. Wan, P. Guo, A.M. Nyström, X.D. Zou, One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. J. Am. Chem. Soc. 138(3), 962–968 (2016). https://doi.org/10.1021/jacs.5b11720
  17. P. Grossen, D. Witzigmann, S. Sieber, J. Huwyler, PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. J. Controlled Release 260, 46–60 (2017). https://doi.org/10.1016/j.jconrel.2017.05.028
  18. X.B. Zhao, P. Liu, Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment-responsive drug delivery system. ACS Appl. Mater. Interfaces 7(1), 166–174 (2015). https://doi.org/10.1021/am505531e
  19. X.B. Zhao, M.Z. Qi, S. Liang, K. Tian, T.T. Zhou, X. Jia, J.G. Li, P. Liu, Synthesis of photo- and pH dual-sensitive amphiphilic copolymer PEG43-b-P(AA76-co-NBA35-co-tBA9) and its micellization as leakage free drug delivery system for UV-triggered intracellular delivery of doxorubicin. ACS Appl. Mater. Interfaces 8(34), 22127–22134 (2016). https://doi.org/10.1021/acsami.6b08935
  20. W.-J. Zhang, C.-Y. Hong, C.-Y. Pan, Polymerization-induced self-assembly of functionalized block copolymer nanoparticles and their application in drug delivery. Macromol. Rapid Commun. 40(2), 1800279 (2018). https://doi.org/10.1002/marc.201800279
  21. Y.T. Xiao, J. Liu, M.Y. Guo, H.G. Zhou, J. Jin et al., Synergistic combination chemotherapy using carrier-free celastrol and doxorubicin nanocrystals for overcoming drug resistance. Nanoscale 10(26), 12639–12649 (2018). https://doi.org/10.1039/c8nr02700e
  22. D.C. Niu, Y.S. Li, J.L. Shi, Silica/organosilica cross-linked block copolymer micelles: a versatile theranostic platform. Chem. Soc. Rev. 46(3), 569–585 (2017). https://doi.org/10.1039/c6cs00495d
  23. Y.L. Miao, Y.D. Qiu, W.J. Yang, Y.Q. Guo, H.W. Hou, Z.Y. Liu, X.B. Zhao, Charge reversible and biodegradable nanocarriers showing dual pH-/reduction-sensitive disintegration for rapid site-specific drug delivery. Colloids Surf. B 169, 313–320 (2018). https://doi.org/10.1016/j.colsurfb.2018.05.026
  24. S.Y. Lee, H. Lee, I. In, S.Y. Park, pH/redox/photo responsive polymeric micelle via boronate ester and disulfide bonds with spiropyran-based photochromic polymer for cell imaging and anticancer drug delivery. Eur. Polym. J. 57, 1–10 (2014). https://doi.org/10.1016/j.eurpolymj.2014.04.020
  25. H. Zhang, J.B. Fei, X.H. Yan, A.H. Wang, J.B. Li, Enzyme-responsive release of doxorubicin from monodisperse dipeptide-based nanocarriers for highly efficient cancer treatment in vitro. Adv. Funct. Mater. 25(8), 1193–1204 (2015). https://doi.org/10.1002/adfm.201403119
  26. B. Louage, Q.L. Zhang, N. Vanparijs, L. Voorhaar, S.V. Casteele et al., Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation. Biomacromolecules 16(1), 336–350 (2015). https://doi.org/10.1021/bm5015409
  27. W.S. Chen, J. Ouyang, H. Liu, M. Chen, K. Zeng et al., Black phosphorus nanosheet-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer. Adv. Mater. 29(5), 1603864 (2017). https://doi.org/10.1002/adma.201603864
  28. M. Qiu, J. Ouyang, H.L. Sun, F.H. Meng, R. Cheng et al., Biodegradable micelles based on poly(ethylene glycol)-b-polylipopeptide copolymer: a robust and versatile nanoplatform for anticancer drug delivery. ACS Appl. Mater. Interfaces. 9(33), 27587–27595 (2017). https://doi.org/10.1021/acsami.7b10533
  29. J.X. Ding, L.H. Chen, C.S. Xiao, L. Chen, X.L. Zhuang, X.S. Chen, Noncovalent interaction-assisted polymeric micelles for controlled drug delivery. Chem. Commun. 50(77), 11274–11290 (2014). https://doi.org/10.1039/c4cc03153a
  30. K.K. Bawa, J.K. Oh, Stimulus-responsive degradable polylactide-based block copolymer nanoassemblies for controlled/enhanced drug delivery. Mol. Pharm. 14(8), 2460–2474 (2017). https://doi.org/10.1021/acs.molpharmaceut.7b00284
  31. G. Saravanakumar, H. Park, J. Kim, D. Park, S. Pramanick, D.H. Kim, W.J. Kim, Miktoarm amphiphilic block copolymer with singlet oxygen-labile stereospecific β-aminoacrylate junction: synthesis, self-assembly, and photodynamically triggered drug release. Biomacromolecules 19(6), 2202–2213 (2018). https://doi.org/10.1021/acs.biomac.8b00290
  32. B. Du, X.Y. Ding, H. Wang, Q. Du, T.G. Xu, J.S. Huang, J. Zhou, G.Y. Cheng, Development of an interactive tumor vascular suppression strategy to inhibit multidrug resistance and metastasis with pH/H2O2 responsive and oxygen-producing nanohybrids. J. Mater. Chem. B 7(31), 4784–4793 (2019). https://doi.org/10.1039/C9TB00546C
  33. X.D. Lin, Y. Fang, Z.H. Tao, X. Gao, T.L. Wang, M.Y. Zhao, S. Wang, Y.Q. Liu, Tumor-microenvironment-induced all-in-one nanoplatform for multimodal imaging-guided chemical and photothermal therapy of cancer. ACS Appl. Mater. Interfaces 11(28), 25043–25053 (2019). https://doi.org/10.1021/acsami.9b07643
  34. Y. Chen, D.L. Ye, M.Y. Wu, H.R. Chen, L.L. Zhang, J.L. Shi, L.Z. Wang, Break-up of two-dimensional MnO2 nanosheets promotes ultrasensitive pH-triggered theranostics of cancer. Adv. Mater. 26(41), 7019–7026 (2014). https://doi.org/10.1002/adma.201402572
  35. Y. Chen, H.R. Chen, J.L. Shi, In vivo bio-safety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv. Mater. 25(23), 3144–3176 (2013). https://doi.org/10.1002/adma.201205292
  36. X.B. Zhao, Y.D. Qiu, Y.L. Miao, Z.Y. Liu, W.J. Yang, H.W. Hou, Unconventional preparation of polymer/amorphous manganese oxide-based biodegradable nanohybrids for low premature release and acid/glutathione-activated magnetic resonance imaging. ACS Appl. Nano Mater. 1(6), 2621–2631 (2018). https://doi.org/10.1021/acsanm.8b00307
  37. X.B. Zhao, L. Liu, X.R. Li, J. Zeng, X. Jia, P. Liu, Biocompatible graphene oxide nanoparticle-based drug delivery platform for tumor microenvironment-responsive triggered release of doxorubicin. Langmuir 30(34), 10419–10429 (2014). https://doi.org/10.1021/la502952f
  38. Q. Chen, L.Z. Feng, J.J. Liu, W.W. Zhu, Z.L. Dong, Y.F. Wu, Z. Liu, Intelligent albumin-MnO2 nanoparticles as pH-/H2O2-responsive dissociable nanocarriers to modulate tumor hypoxia for effective combination therapy. Adv. Mater. 28(33), 7129–7136 (2016). https://doi.org/10.1002/adma.201601902
  39. H. Xia, J.K. Feng, H.L. Wang, M.O. Lai, L. Lu, MnO2 nanotube and nanowire arrays by electrochemical deposition for supercapacitors. J. Power Sources 195(13), 4410–4413 (2010). https://doi.org/10.1016/j.jpowsour.2010.01.075
  40. Y.A. Mastrikov, E. Heifets, E.A. Kotomin, J. Maiera, Atomic, electronic and thermodynamic properties of cubic and orthorhombic LaMnO3 surfaces. Surf. Sci. 603(2), 326–335 (2009). https://doi.org/10.1016/j.susc.2008.11.034
  41. S.L. Canning, G.N. Smith, S.P. Armes, A critical appraisal of RAFT-mediated polymerization-induced self-assembly. Macromolecules 49(6), 1985–2001 (2016). https://doi.org/10.1021/acs.macromol.5b02602
  42. L.L. Wang, C. Zeng, H. Xu, P.C. Yin, D.C. Chen et al., A highly soluble, crystalline covalent organic framework compatible with device implementation. Chem. Sci. 10(4), 1023–1028 (2019). https://doi.org/10.1039/C8SC04255A
  43. J.M. Harris, R.B. Chess, Effect of PEGylation on pharmaceuticals. Nat. Rev. Drug Discov. 2(3), 214–221 (2003). https://doi.org/10.1038/nrd1033
  44. Q. Liao, Q.L. Shao, H.Y. Wang, G. Qiu, X.H. Lu, Hydroxypropylcellulose templated synthesis of surfactant-free poly(acrylic acid) nanogels in aqueous media. Carbohydr. Polym. 87(4), 2648–2654 (2012). https://doi.org/10.1016/j.carbpol.2011.11.056
  45. W.J. Yang, X.B. Zhao, Glutathione-induced structural transform of double-cross-linked PEGylated nanogel for efficient intracellular anticancer drug delivery. Mol. Pharm. 16(6), 2826–2837 (2019). https://doi.org/10.1021/acs.molpharmaceut.9b00467
  46. A. Pugazhendhi, T.N.J.I. Edison, B.K. Velmurugan, J.A. Jacob, I. Karuppusamy, Toxicity of doxorubicin (dox) to different experimental organ systems. Life Sci. 200, 26–30 (2018). https://doi.org/10.1016/j.lfs.2018.03.023
Read More
Author biographies are not available.
Download this PDF file
PDF SUPPLEMENTARY MATERIAL
Statistic
Read Counter : 4655 Download : 3518

Most read articles by the same author(s)