Therapeutic delivery · 2025
Development and evaluation of targeted liposomes for improved doxorubicin and quercetin delivery for MDR breast cancer.
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Gautam Shreastha, Maurya Rashmi, Patel Preeti, Gupta Ghanshyam Das, Kurmi Balak Das
Аннотация
INTRODUCTION: Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Despite the availability of chemotherapeutics, such as doxorubicin, treatment efficacy, is often hampered by multidrug resistance, largely driven by efflux transporters like P-glycoprotein.
AIM & OBJECTIVES: This study aimed to develop and evaluate a targeted liposomal system for the co-delivery of doxorubicin and quercetin to overcome multidrug resistance in breast cancer cells. The objective was to enhance therapeutic efficacy while minimizing systemic toxicity.
METHOD: Liposomes were prepared using the thin-film hydration method and optimized via Box-Behnken Design. Two formulations, doxorubicin and quercetin liposomes (DOX-QCT-LIPO) and Trastuzumab conjugated (TmAb-DOX-QCT-LIPO), were characterized for vesicle size, PDI, and entrapment efficiency. Their cytotoxicity (MTT assay) and cellular uptake (FACS) were tested in MCF-7 and MCF-7/ADR cell lines.
RESULTS: Optimized formulations exhibited nanoscale size, uniform distribution, and high drug encapsulation. Tmab-DOX-QCT-LIPO showed significantly enhanced cytotoxicity and uptake in MDR breast cancer cells compared to free DOX and non-targeted liposomes, indicating effective bypass of efflux mechanisms via HER2-mediated endocytosis.
CONCLUSION: TmAb-DOX-QCT-LIPO demonstrated superior anticancer potential by integrating dual-drug loading, P-gp inhibition, and HER2-targeted uptake, offering a promising therapeutic strategy against MDR breast cancer.
AIM & OBJECTIVES: This study aimed to develop and evaluate a targeted liposomal system for the co-delivery of doxorubicin and quercetin to overcome multidrug resistance in breast cancer cells. The objective was to enhance therapeutic efficacy while minimizing systemic toxicity.
METHOD: Liposomes were prepared using the thin-film hydration method and optimized via Box-Behnken Design. Two formulations, doxorubicin and quercetin liposomes (DOX-QCT-LIPO) and Trastuzumab conjugated (TmAb-DOX-QCT-LIPO), were characterized for vesicle size, PDI, and entrapment efficiency. Their cytotoxicity (MTT assay) and cellular uptake (FACS) were tested in MCF-7 and MCF-7/ADR cell lines.
RESULTS: Optimized formulations exhibited nanoscale size, uniform distribution, and high drug encapsulation. Tmab-DOX-QCT-LIPO showed significantly enhanced cytotoxicity and uptake in MDR breast cancer cells compared to free DOX and non-targeted liposomes, indicating effective bypass of efflux mechanisms via HER2-mediated endocytosis.
CONCLUSION: TmAb-DOX-QCT-LIPO demonstrated superior anticancer potential by integrating dual-drug loading, P-gp inhibition, and HER2-targeted uptake, offering a promising therapeutic strategy against MDR breast cancer.