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Polymer Bulletin

, Volume 76, Issue 5, pp 2471–2479 | Cite as

Amphiphilic polymer to improve polyplex stability for enhanced transfection efficiency

  • Yanfen Zheng
  • Xiaoyuan Wang
  • Funan Qiu
  • Lu YinEmail author
Original Paper
  • 45 Downloads

Abstract

The clinical applications of cationic polymer-based non-viral gene carriers are usually hindered by the instability of polyplex or complex between these cationic polymers and anionic genes. In order to increase the stability, an amphiphilic cationic block copolymer PHB-b-PDMAEMA was designed to form cationic micelle, which comprised hydrophobic poly[(R)-3-hydroxybutyrate] (PHB) block and cationic poly(2-(dimethylamino)ethyl methacrylate) (DMAEMA) block. Interestingly, this cationic micelle after complex formation with plasmid deoxyribonucleic acid (pDNA) exhibited enhanced stability within 24 h and showed improved gene transfection performance than PDMAEMA only or non-viral transfection gold standard poly(ethylene imine) with molecular weight of 25 kDa (PEI-25k). In short, the design of cationic amphiphilic polymer, with micelle formation ability to enhance stability of polyplex, might greatly benefit the designs of non-viral cationic polymers as potential gene vectors.

Notes

Funding

Funding was provided by Xiamen Science and Technology Program Grant (Grant No. 3502Z20174025), Fujian Health-Education Research Grant (Grant No. WKJ2016-2-03), and Fujian Provincial Natural Science Foundation (Grant No. 2015J01416).

References

  1. 1.
    Xia JL, Chen J, Lin L, Guo ZP, Han B, Yang HY, Feng ZC, Tian HY (2016) Sulfathiazole grafted PEG–PLL as pH-sensitive shielding system for cationic gene delivery. Polym Bull 73(12):3503–3511CrossRefGoogle Scholar
  2. 2.
    Badwaik VD, Aicart E, Mondjinou YA, Johnson MA, Bowman VD, Thompson DH (2016) Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-beta-cyclodextrin: PEG–PPG–PEG polyrotaxane vectors. Biomaterials 84:86–98CrossRefGoogle Scholar
  3. 3.
    Li Z, Liu X, Chen X, Chua MX, Wu Y-L (2017) Targeted delivery of Bcl-2 conversion gene by MPEG–PCL–PEI–FA cationic copolymer to combat therapeutic resistant cancer. Mater Sci Eng C 76:66–72CrossRefGoogle Scholar
  4. 4.
    Liu X, Chen X, Chua MX, Li Z, Loh XJ, Wu Y-L (2017) Injectable supramolecular hydrogels as delivery agents of Bcl-2 conversion gene for the effective shrinkage of therapeutic resistance tumors. Adv Healthcare Mater 6(11):1700159CrossRefGoogle Scholar
  5. 5.
    Wu Y-L, Engl W, Hu B, Cai P, Leow WR, Tan NS, Lim CT, Chen X (2017) Nanomechanically visualizing drug–cell interaction at the early stage of chemotherapy. ACS Nano 11(7):6996–7005CrossRefGoogle Scholar
  6. 6.
    Cheng H, Wu Z, Wu C, Wang X, Liow SS, Li Z, Wu Y-L (2018) Overcoming STC2 mediated drug resistance through drug and gene co-delivery by PHB-PDMAEMA cationic polyester in liver cancer cells. Mater Sci Eng C 83:210–217CrossRefGoogle Scholar
  7. 7.
    Liu X, Li Z, Loh XJ, Chen K, Li Z, Wu Y-L (2018) Targeted and sustained corelease of chemotherapeutics and gene by injectable supramolecular hydrogel for drug-resistant cancer therapy. Macromol Rapid Commun 39:1800117Google Scholar
  8. 8.
    Cheng H, Fan X, Wu C, Wang X, Wang L-J, Loh XJ, Li Z, Wu Y-L (2018) Cyclodextrin-based star-like amphiphilic cationic polymer as a potential pharmaceutical carrier in macrophages. Macromol Rapid Commun 39:1800207CrossRefGoogle Scholar
  9. 9.
    Nishiyama N, Bae Y, Miyata K, Fukushima S, Kataoka K (2005) Smart polymeric micelles for gene and drug delivery. Drug Discov Today Technol 2(1):21–26CrossRefGoogle Scholar
  10. 10.
    Wang Y, Ke CY, Weijie Beh C, Liu SQ, Goh SH, Yang YY (2007) The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection. Biomaterials 28(35):5358–5368CrossRefGoogle Scholar
  11. 11.
    Xiang Y, Oo NNL, Lee JP, Li Z, Loh XJ (2017) Recent development of synthetic nonviral systems for sustained gene delivery. Drug Discov Today 22(9):1318–1335CrossRefGoogle Scholar
  12. 12.
    Lu X, Jia F, Tan X, Wang D, Cao X, Zheng J, Zhang K (2016) Effective antisense gene regulation via noncationic, polyethylene glycol brushes. J Am Chem Soc 138(29):9097–9100CrossRefGoogle Scholar
  13. 13.
    Fan X, Chung JY, Lim YX, Li Z, Loh XJ (2016) Review of adaptive programmable materials and their bioapplications. ACS Appl Mater Interfaces 8(49):33351–33370CrossRefGoogle Scholar
  14. 14.
    Li Z, Loh XJ (2017) Recent advances of using polyhydroxyalkanoate-based nanovehicles as therapeutic delivery carriers. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9(3):e1429CrossRefGoogle Scholar
  15. 15.
    Fan XS, Li ZBA, Loh XJ (2016) Recent development of unimolecular micelles as functional materials and applications. Polym Chem 7(38):5898–5919CrossRefGoogle Scholar
  16. 16.
    Li ZB, Wong SL (2017) Functionalization of 2D transition metal dichalcogenides for biomedical applications. Mat Sci Eng C Mater 70:1095–1106CrossRefGoogle Scholar
  17. 17.
    Ding CZ, Li ZB (2017) A review of drug release mechanisms from nanocarrier systems. Mat Sci Eng C Mater 76:1440–1453CrossRefGoogle Scholar
  18. 18.
    Zheng C, Gao H, Yang D-P, Liu M, Cheng H, Wu Y-L, Loh XJ (2017) PCL-based thermo-gelling polymers for in vivo delivery of chemotherapeutics to tumors. Mater Sci Eng C 74:110–116CrossRefGoogle Scholar
  19. 19.
    Loh XJ, Ong SJ, Tung YT, Choo HT (2013) Co-delivery of drug and DNA from cationic dual-responsive micelles derived from poly (DMAEMA-co-PPGMA). Mater Sci Eng C Mater Biol Appl 33(8):4545–4550CrossRefGoogle Scholar
  20. 20.
    Cheng H, Fan X, Wang X, Ye E, Loh XJ, Li Z, Wu Y-L (2018) Hierarchically self-assembled supramolecular host–guest delivery system for drug resistant cancer therapy. Biomacromolecules 19(6):1926–1938CrossRefGoogle Scholar
  21. 21.
    Wang X, Liow SS, Wu Q, Li C, Owh C, Li Z, Loh XJ, Wu Y-L (2017) Codelivery for paclitaxel and Bcl-2 conversion gene by PHB-PDMAEMA amphiphilic cationic copolymer for effective drug resistant cancer therapy. Macromol Biosci 17(11):1700186CrossRefGoogle Scholar
  22. 22.
    Loh XJ, Ong SJ, Tung YT, Teng CH (2013) Dual responsive micelles based on poly[(R)-3-hydroxybutyrate] and poly(2-(di-methylamino)ethyl methacrylate) for effective doxorubicin delivery. Polym Chem 4(8):2564–2574CrossRefGoogle Scholar
  23. 23.
    Loh XJ, Ong SJ, Tung YT, Choo HT (2013) Incorporation of poly[(R)-3-hydroxybutyrate] into cationic copolymers based on poly(2-(dimethylamino)ethyl methacrylate) to improve gene delivery. Macromol Biosci 13(8):1092–1099CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Stomatological HospitalXiamen Medical CollegeXiamenPeople’s Republic of China
  2. 2.School of Pharmaceutical SciencesXiamen UniversityXiamenPeople’s Republic of China
  3. 3.Provincial Clinical CollegeFujian Medical UniversityFuzhouPeople’s Republic of China
  4. 4.Department of Hepatobiliary SurgeryFujian Provincial HospitalFuzhouPeople’s Republic of China

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