Back to Search
Start Over
Dual-responsive TPGS crosslinked nanocarriers to overcome multidrug resistance.
- 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.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Apoptosis drug effects
Cell-Penetrating Peptides chemistry
Cell-Penetrating Peptides pharmacokinetics
Doxorubicin chemistry
Doxorubicin pharmacokinetics
Drug Carriers pharmacokinetics
Drug Liberation
Female
Fluorescence
Humans
MCF-7 Cells
Mice, Inbred BALB C
Micelles
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacokinetics
Vitamin E pharmacokinetics
Vitamin E therapeutic use
Antineoplastic Agents therapeutic use
Doxorubicin therapeutic use
Drug Carriers chemistry
Drug Resistance, Multiple drug effects
Drug Resistance, Neoplasm drug effects
Neoplasms drug therapy
Subjects
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