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Colloid and Polymer Science

, Volume 297, Issue 2, pp 225–238 | Cite as

Redox-responsive comparison of diselenide micelles with disulfide micelles

  • Longshuai Zhang
  • Yuancheng Liu
  • Kui Zhang
  • Yuanwei Chen
  • Xianglin LuoEmail author
Original Contribution
  • 49 Downloads

Abstract

Redox-responsive block copolymer micelles have been studied extensively as drug carriers. In this study, tri-block copolymers, methoxyl poly(ethylene glycol)-b-poly(ε-caprolactone)-SeSe-b-poly(ε-caprolactone)-b-methoxyl-poly(ethylene glycol) (mPEG-PCL-SeSe-PCL-mPEG) and methoxyl poly(ethyleneglyco)-b-poly(ε-caprolactone)-SS-b- poly(ε-caprolactone)-b-methoxyl-poly(ethylene glycol) (mPEG-PCL-SS-PCL-mPEG), were synthesized to investigate the redox sensitivity differences between diselenide and disulfide micelles. The changes of micelles in size and structure were investigated under conditions with glutathione (GSH) or H2O2. The results showed that the size and PDI of (mPEG-PCL-Se)2 micelles presented more significant variations under redox condition in comparison with (mPEG-PCL-S)2 micelles. The DOX released faster and more from diselenide micelles than disulfide micelles. The half maximal inhibitory concentration (IC50) of (mPEG-PCL-Se)2/DOX micelles was lower than that of (mPEG-PCL-S)2/DOX micelles against 4T1 and Hela cells. The amount of intracellular drug release from diselenide micelles was higher than from disulfide micelles in Hela cells with GSH 4.6 mM. Therefore, the (mPEG-PCL-Se)2 micelles similar to (mPEG-PCL-S)2 micelles are stimuli-responsive and may be more sensitive drug carriers.

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The polymer micelles containing diselenide or disulfide with similar molecular structure are prepared to investigate the redox sensitivity differences. Both micelles have redox sensitivity and capability to enter into 4T1 cells and Hela cells. (mPEG-PCL-Se)2 micelles present more significant sensitivity and lower IC50 against cancer cells than disulfide micelles. The diselenide micelles may be more sensitive platforms and be suit to tumor cells in which GSH is less than 10 mM.

Keywords

Redox-responsive polymer micelles Glutathione concentration in cancer cells Diselenide Disulfide Redox sensitivity 

Notes

Acknowledgments

The authors acknowledge the testing services supplied by Analytical and Testing Center of Sichuan University and the help of laboratory members.

Funding information

This work was financially supported by the National Natural Science Foundation of China (No. 51673129, No. 51473099, and No. 51273125)

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

396_2018_4457_MOESM1_ESM.pdf (529 kb)
ESM 1 (PDF 528 kb)

References

  1. 1.
    Hu J, Sheng Y, Shi J, Yu B, Yu Z, Liao G (2017) Long circulating polymeric nanoparticles for gene/drug delivery. Curr Drug Metab 19:723–738.  https://doi.org/10.2174/1389200219666171207120643 CrossRefGoogle Scholar
  2. 2.
    You X, Kang Y, Hollett G, Chen X, Zhao W, Gu Z, Wu J (2016) Polymeric nanoparticles for colon cancer therapy: overview and perspectives. J Mater Chem B 4(48):7779–7792.  https://doi.org/10.1039/C6TB01925K CrossRefGoogle Scholar
  3. 3.
    Biswas S, Kumari P, Lakhani PM, Ghosh B (2016) Recent advances in polymeric micelles for anti-cancer drug delivery. Eur J Pharm Sci 83:184–202.  https://doi.org/10.1016/j.ejps.2015.12.031 CrossRefGoogle Scholar
  4. 4.
    Gothwal A, Khan I, Gupta U (2016) Polymeric micelles: recent advancements in the delivery of anticancer drugs. Pharm Res 33(1):18–39.  https://doi.org/10.1007/s11095-015-1784-1 CrossRefGoogle Scholar
  5. 5.
    Cheng R, Meng F, Deng C, Zhong Z (2015) Bioresponsive polymeric nanotherapeutics for targeted cancer chemotherapy. Nano Today 10(5):656–670.  https://doi.org/10.1016/j.nantod.2015.09.005 CrossRefGoogle Scholar
  6. 6.
    Jhaveri A, Deshpande P, Torchilin V (2014) Stimuli-sensitive nanopreparations for combination cancer therapy. J Control Release 190:352–370.  https://doi.org/10.1016/j.jconrel.2014.05.002 CrossRefGoogle Scholar
  7. 7.
    Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P (2013) Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chem Soc Rev 42(3):1147–1235.  https://doi.org/10.1039/C2CS35265F CrossRefGoogle Scholar
  8. 8.
    Zhang X, Han L, Liu M, Wang K, Tao L, Wan Q, Wei Y (2017) Recent progress and advances in redox-responsive polymers as controlled delivery nanoplatforms. Mater Chem Front 1(5):807–822.  https://doi.org/10.1039/C6QM00135A CrossRefGoogle Scholar
  9. 9.
    Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z (2011) Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J Control Release 152(1):2–12.  https://doi.org/10.1016/j.jconrel.2011.01.030 CrossRefGoogle Scholar
  10. 10.
    Deng B, Ma P, Xie Y (2015) Reduction-sensitive polymeric nanocarriers in cancer therapy: a comprehensive review. Nanoscale 7(30):12773–12795.  https://doi.org/10.1039/C5NR02878G CrossRefGoogle Scholar
  11. 11.
    Lu Y, Mo R, Tai W, Sun W, Pacardo DB, Qian C, Shen Q, Ligler FS, Gu Z (2014) Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery. Chem Commun 50(95):15105–15108.  https://doi.org/10.1039/C4CC07004F CrossRefGoogle Scholar
  12. 12.
    Sun H, Meng F, Cheng R, Deng C, Zhong Z (2013) Reduction-responsive polymeric micelles and vesicles for triggered intracellular drug release. Antioxid Redox Signal 21(5):755–767.  https://doi.org/10.1089/ars.2013.5733 CrossRefGoogle Scholar
  13. 13.
    Wu Z, Cai M, Cao J, Zhang J, Luo X (2017) Effects of copolymer component on the properties of phosphorylcholine micelles. Int J Nanomedicine 12:487–500.  https://doi.org/10.2147/IJN.S118197 CrossRefGoogle Scholar
  14. 14.
    Cerritelli S, Velluto D, Hubbell JA (2007) PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. Biomacromolecules 8(6):1966–1972.  https://doi.org/10.1021/bm070085x CrossRefGoogle Scholar
  15. 15.
    Kim JO, Sahay G, Kabanov AV, Bronich TK (2010) Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents. Biomacromolecules 11(4):919–926.  https://doi.org/10.1021/bm9013364 CrossRefGoogle Scholar
  16. 16.
    Yue D, Cheng G, He Y, Nie Y, Jiang Q, Cai X, Gu Z (2014) Influence of reduction-sensitive diselenide bonds and disulfide bonds on oligoethylenimine conjugates for gene delivery. J Mater Chem B 2(41):7210–7221.  https://doi.org/10.1039/C4TB00757C CrossRefGoogle Scholar
  17. 17.
    Xu H, Cao W, Zhang X (2013) Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics. Acc Chem Res 46(7):1647–1658.  https://doi.org/10.1021/ar4000339 CrossRefGoogle Scholar
  18. 18.
    H GWH (1972) Selenium containing polymers. USGoogle Scholar
  19. 19.
    Ma N, Li Y, Xu H, Wang Z, Zhang X (2010) Dual redox responsive assemblies formed from diselenide block copolymers. J Am Chem Soc 132(2):442–443.  https://doi.org/10.1021/ja908124g CrossRefGoogle Scholar
  20. 20.
    Zeng X, Zhou X, Li M, Wang C, Xu J, Ma D, Xue W (2015) Redox poly(ethylene glycol)-b-poly(l-lactide) micelles containing diselenide bonds for effective drug delivery. J Mater Sci Mater Med 26(9):234.  https://doi.org/10.1007/s10856-015-5573-5 CrossRefGoogle Scholar
  21. 21.
    Wei C, Zhang Y, Xu H, Xu Y, Xu Y, Lang M (2016) Well-defined labile diselenide-centered poly(ε-caprolactone)-based micelles for activated intracellular drug release. J Mater Chem B 4(29):5059–5067.  https://doi.org/10.1039/C6TB01040G CrossRefGoogle Scholar
  22. 22.
    Xu Q, He C, Xiao C, Chen X (2016) Reactive oxygen species (ROS) responsive polymers for biomedical applications. Macromol Biosci 16(5):635–646.  https://doi.org/10.1002/mabi.201500440 CrossRefGoogle Scholar
  23. 23.
    Wei C, Xu Y, Yan B, Hou J, Du Z, Lang M (2018) Well-defined selenium-containing aliphatic polycarbonates via lipase-catalyzed ring-opening polymerization of selenic macrocyclic carbonate monomer. ACS Macro Lett 7(3):336–340.  https://doi.org/10.1021/acsmacrolett.8b00039 CrossRefGoogle Scholar
  24. 24.
    Wei C, Zhang Y, Yan B, Du Z, Lang M (2017) A versatile strategy to main chain sulfur/selenium-functionalized polycarbonates by macro-ring closure of diols and subsequent ring-opening polymerization. Chem Eur J 24(4):789–792.  https://doi.org/10.1002/chem.201704301 CrossRefGoogle Scholar
  25. 25.
    Wei C, Zhang Y, Song Z, Xia Y, Xu H, Lang M (2017) Enhanced bioreduction-responsive biodegradable diselenide-containing poly(ester urethane) nanocarriers. Biomater Sci 5(4):669–677.  https://doi.org/10.1039/C6BM00960C CrossRefGoogle Scholar
  26. 26.
    Li Y, Leng M, Cai M, Huang L, Chen Y, Luo X (2017) pH responsive micelles based on copolymers mPEG-PCL-PDEA: the relationship between composition and properties. Colloids Surf B: Biointerfaces 154:397–407.  https://doi.org/10.1016/j.colsurfb.2017.03.045 CrossRefGoogle Scholar
  27. 27.
    Qiu M, Ouyang J, Sun H, Meng F, Cheng R, Zhang J, Cheng L, Lan Q, Deng C, Zhong Z (2017) 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.  https://doi.org/10.1021/acsami.7b10533 CrossRefGoogle Scholar
  28. 28.
    Cai Y, Li S, Cai M, Chen Y, Luo X (2017) Cellular uptake of pH/reduction responsive phosphorylcholine micelles. New J Chem 41(20):11828–11838.  https://doi.org/10.1039/C7NJ02484C CrossRefGoogle Scholar
  29. 29.
    Jiang H, Ma J, Li C (2012) Hierarchical porous NiCo2O4 nanowires for high-rate supercapacitors. Chem Commun 48(37):4465–4467.  https://doi.org/10.1039/C2CC31418E CrossRefGoogle Scholar
  30. 30.
    Wan H, Jiang J, Yu J, Xu K, Miao L, Zhang L, Chen H, Ruan Y (2013) NiCo2S4 porous nanotubes synthesis via sacrificial templates: high-performance electrode materials of supercapacitors. CrystEngComm 15(38):7649–7651.  https://doi.org/10.1039/C3CE41243A CrossRefGoogle Scholar
  31. 31.
    Liu L, Li C, Li X, Yuan Z, An Y, He B (2001) Biodegradable polylactide/poly(ethylene glycol)/polylactide triblock copolymer micelles as anticancer drug carriers. J Appl Polym Sci 80(11):1976–1982.  https://doi.org/10.1002/app.1295 CrossRefGoogle Scholar
  32. 32.
    Chen XTY (2009) The synthesis and structure analysis of the complexes between flavonoids and selenide (in Chinese). J Wenzhou Med Coll 39(1)Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Longshuai Zhang
    • 1
  • Yuancheng Liu
    • 1
  • Kui Zhang
    • 1
  • Yuanwei Chen
    • 1
  • Xianglin Luo
    • 1
    • 2
    Email author
  1. 1.College of Polymer Science and EngineeringSichuan UniversityChengduPeople’s Republic of China
  2. 2.State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengduPeople’s Republic of China

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