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Bioreducible Micelles Self-Assembled from Amphiphilic Hyperbranched Multiarm Copolymer for Glutathione-Mediated Intracellular Drug Delivery
Abstract
A new type of biodegradable micelles for glutathione-mediated intracellular drug delivery was developed on the basis of an amphiphilic hyperbranched multiarm copolymer (H40-star-PLA-SS-PEP) with disulfide linkages between the hydrophobic polyester core and hydrophilic polyphosphate arms. The resulting copolymers were characterized by nuclear magnetic resonance (NMR), Fourier transformed infrared (FTIR), gel permeation chromatography (GPC), and differential scanning calorimeter (DSC) techniques. Benefiting from amphiphilic structure, H40-star-PLA-SS-PEP was able to self-assemble into micelles in aqueous solution with an average diameter of 70 nm. Moreover, the hydrophilic polyphosphate shell of these micelles could be detached under reduction-stimulus by in vitro evaluation, which resulted in a rapid drug release due to the destruction of micelle structure. The glutathione-mediated intracellular drug delivery was investigated against a Hela human cervical carcinoma cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that H40-star-PLA-SS-PEP micelles exhibited a faster drug release in glutathione monoester (GSH-OEt) pretreated Hela cells than that in the nonpretreated cells. Cytotoxicity assay of the doxorubicin-loaded (DOX-loaded) micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated Hela cells than that of the nonpretreated ones. As expected, the DOX-loaded micelles showed lower inhibition against 0.1 mM of buthionine sulfoximine (BSO) pretreated Hela cells. These reduction-responsive and biodegradable micelles show a potential to improve the antitumor efficacy of hydrophobic chemotherapeutic drugs.
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Citations
Cites
Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery
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Recent progress in polyphosphoesters: From controlled synthesis to biomedical applications
Wang, Y., Yuan, Y., Du, J., Yang, X., & Wang, J. (2009) · Macromolecular Bioscience · doi:10.1002/mabi.200900253 · Cited by 203
Cited by
Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00346 · Cited by 3,070
Redox-responsive polymers for drug delivery: from molecular design to applications
Huo, M., Yuan, J., Tao, L., & Wei, Y. (2014) · Polym. Chem. · doi:10.1039/c3py01192e · Cited by 561
Zhang, Q., Re Ko, N., & Kwon Oh, J. (2012) · Chemical Communications · doi:10.1039/c2cc32408c · Cited by 395
Bioapplications of hyperbranched polymers
Wang, D., Zhao, T., Zhu, X., Yan, D., & Wang, W. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00229f · Cited by 301
Self-citationCui, C., Xue, Y.-N., Wu, M., Zhang, Y., Yu, P., Liu, L., Zhuo, R.-X., & Huang, S.-W. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.01.101 · Cited by 169
Metadata
- Authors
- Liu, J., Pang, Y., Huang, W., Huang, X., Meng, L., Zhu, X., Zhou, Y., & Yan, D.
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-04-14
- Volume
- 12
- Issue
- 5
- Pages
- 1567-1577
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- OpenAlex
- W2061719532
- Cited by
- 189
- References
- 3
- FWCI
- 21.00
- Type
- journal article
- Language
- en
- Open access
- closed
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- Liu, J., Pang, Y., Huang, W., Huang, X., Meng, L., Zhu, X., Zhou, Y., & Yan, D. (2011). Bioreducible Micelles Self-Assembled from Amphiphilic Hyperbranched Multiarm Copolymer for Glutathione-Mediated Intracellular Drug Delivery. Biomacromolecules. https://doi.org/10.1021/bm200275j
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