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Lapatinib-loaded acidity-triggered charge switchable polycarbonate-doxorubicin conjugate micelles for synergistic breast cancer chemotherapy.
- Source :
- Acta Biomaterialia; Dec2020, Vol. 118, p182-195, 14p
- Publication Year :
- 2020
-
Abstract
- Stimulus-responsive nanosystem is a powerful method to improve the bioavailability and reduce the side effects of anticancer agents. In the present study, a customized dual pH-responsive micellar nanoplatform (DOX+LAP-M) based on polycarbonate-doxorubicin conjugate micelles was prepared to co-deliver the chemotherapeutic agent lapatinib for inhibiting tumor growth and metastasis. DOX+LAP-M micelles with spherical morphology had a size of ~112 nm and had an initial negative surface charge, which are favorable characteristics for long-term circulation in the blood. Once the micelles accumulated in tumor tissues, the intrinsic tumor extracellular acidity triggered the charge switch of DOX+LAP-M micelles from -1 to 9 mV, thereby facilitating cell internalization and tumor penetration. Subsequently, the pH-sensitive micellar core accelerated the release of doxorubicin and lapatinib in the acidic intracellular environment. DOX+LAP-M micelles effectively inhibited the proliferation, migration, and invasion of 4T1 cells in vitro ; furthermore, the administration of DOX+LAP-M micelles in 4T1 xenograft-bearing mice suppressed solid tumor growth with an inhibitory rate of 90.2% and significantly decreased pulmonary metastatic nodules, without significant systemic toxicity. This multifunctional micellar system has high potential for clinical cancer therapy. Image, graphical abstract [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17427061
- Volume :
- 118
- Database :
- Supplemental Index
- Journal :
- Acta Biomaterialia
- Publication Type :
- Academic Journal
- Accession number :
- 147113886
- Full Text :
- https://doi.org/10.1016/j.actbio.2020.09.051