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Dual-responsive TPGS crosslinked nanocarriers to overcome multidrug resistance.

Authors :
Li L
Liu T
Liao JX
Zhang ZY
Song DB
Wang GH
Source :
Journal of materials chemistry. B [J Mater Chem B] 2020 Sep 23; Vol. 8 (36), pp. 8383-8394.
Publication Year :
2020

Abstract

Efficient delivery of chemotherapeutic agents into tumor cells and reversal of chemoresistance are crucially important to enhance cancer therapy. We fabricated pH/redox dual responsive nanocarriers based on cell penetrating peptides (TAT) functionalized TPGS (cTAT-TPGS) and polypeptide (PEG-b-poly(aspartic-lipoic acid), PPAL) to reduce the permanent drug release and overcome multidrug resistance. TAT was used to functionalize TPGS and shielded by pH-responsive fatty acids, and polypeptides with lipoic acid side chains (PPAL) were synthesized. Reversibly crosslinked hybrid micelles (RCMs) were fabricated based on cTAT-TPGS and PPAL. RCMs nanocarriers exhibited acid-responsive charge reversal and redox-responsive drug release. The in vitro results showed that the RCMs could be efficiently internalized by the MCF-7/ADR cells in an acidic microenvironment and inhibited the DOX efflux, causing a higher cytotoxicity than non-crosslinked nanocarriers. Furthermore, the dual-responsive structure effectively prolonged the circulation time of RCM nanocarriers and achieved a high level of accumulation in cancer cells in vivo, leading to much more effective inhibition of tumor growth. The DOX-loaded RCMs also showed excellent biosafety, especially for the myocardium tissue. This novel strategy provided an effective platform for drug target delivery and reversal of MDR.

Details

Language :
English
ISSN :
2050-7518
Volume :
8
Issue :
36
Database :
MEDLINE
Journal :
Journal of materials chemistry. B
Publication Type :
Academic Journal
Accession number :
32803210
Full Text :
https://doi.org/10.1039/d0tb01140a