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Updated: Apr 3, 2026
Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Gambogic acid-loaded pH-sensitive mixed micelles for overcoming breast cancer resistance
Shengpeng Wang1, Yu Yang1, Yitao Wang1
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
Abstract:
Multidrug resistance (MDR) is one of the major obstacles to the successful treatment of breast cancer. The overexpression of drug efflux transporters such as P-glycoprotein (P-gp) and of anti-apoptotic proteins like survivin are the major causes of MDR. Here, we developed a gambogic acid (GA)-loaded mixed micelle system made of poly(ethylene glycol)-poly(L-histidine)-poly(D,L-lactide-co-glycolide) (PEG-pHis-PLGA) and D-α-tocopheryl polyethylene glycol 1000 (TPGS) that is potentially useful for overcoming MDR by integrating the beneficial effects of pH-sensitive behavior, P-gp inhibition, and down-regulation of anti-apoptotic proteins. The therapeutic potential and mechanism of action of GA-loaded pH-sensitive mixed micelles were examined in drug-sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. The resulting GA-loaded mixed micelles with an average size of 190.1 nm were stable at pH 7.4, but dissociated rapidly in a weakly acidic environment (pH 5.5). The GA-loaded mixed micelles increased the cell cytotoxicity against both MCF-7 and MCF-7/ADR cells, which was associated with enhanced apoptosis. In addition, the GA-loaded mixed micelles down-regulated the expression of the anti-apoptotic proteins survivin and Bcl-2, and inhibited the expression and activity of P-gp in MCF-7/ADR cells. Our results indicate that this system could overcome drug resistant in breast cancer by targeting distinct mechanisms, which may facilitate the translation of the GA-mediated effects into clinical benefits.
Insights
This study presents a novel gambogic acid (GA)-loaded micelle system to combat multidrug resistance (MDR) in breast cancer. The system effectively enhances cytotoxicity and overcomes resistance by targeting P-glycoprotein and anti-apoptotic proteins.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Drug Delivery
Background:
- Multidrug resistance (MDR) is a major challenge in breast cancer treatment.
- Overexpression of P-glycoprotein (P-gp) and survivin contributes significantly to MDR.
- Developing novel strategies to overcome MDR is crucial for improving patient outcomes.
Purpose of the Study:
- To develop and evaluate a gambogic acid (GA)-loaded pH-sensitive mixed micelle system for overcoming breast cancer MDR.
- To investigate the therapeutic potential and mechanism of action of this novel nanocarrier system.
Main Methods:
- Formulation of GA-loaded mixed micelles using PEG-pHis-PLGA and TPGS.
- Characterization of micelle size, stability, and pH-sensitive dissociation.
- Assessment of cytotoxicity, apoptosis, and protein expression in drug-sensitive (MCF-7) and drug-resistant (MCF-7/ADR) breast cancer cells.
Main Results:
- GA-loaded mixed micelles exhibited pH-sensitive dissociation at acidic conditions (pH 5.5).
- The micelles significantly increased cytotoxicity and apoptosis in both MCF-7 and MCF-7/ADR cells.
- The system effectively down-regulated survivin and Bcl-2, and inhibited P-gp expression and activity in resistant cells.
Conclusions:
- The GA-loaded pH-sensitive mixed micelle system demonstrates potential for overcoming breast cancer MDR.
- This nanocarrier system targets multiple mechanisms, including P-gp inhibition and apoptosis induction.
- The findings suggest a promising avenue for translating GA-mediated effects into clinical benefits for breast cancer patients.
