TPGS and chondroitin sulfate dual-modified lipid-albumin nanosystem for targeted delivery of chemotherapeutic agent against multidrug-resistant cancer
Multidrug resistance (MDR) remains the primary issue leading to the failure of chemotherapy. In this study, a d-α-tocopherol polyethylene 1000 glycol succinate (TPGS) and chondroitin sulfate (CS) dual-modified lipid-albumin nanosystem was constructed for targeted delivery of paclitaxel (PTX) in treating MDR cancer.
Highlights
A lipid-albumin nanosystem was developed to treat multidrug resistance cancer.
Introduction of chondroitin sulfate promoted CD44-mediated endocytosis.
TAL/PTX@CS showed notable antitumor efficacy and good biosafety.
The obtained nanosystem (TLA/PTX@CS) had an average size of around 176 nm and a negative zeta potential of around −18 mV. TPGS was confirmed to improve the intracellular accumulation of PTX and facilitate the mitochondrial-targeting of lipid-albumin nanosystem. Functionalized with the outer CS shell, TLA/PTX@CS entered MDR breast cancer (MCF-7/MDR) cells via CD44 receptor-mediated endocytosis. CS shell was degraded by concentrated hyaluronidase in the lysosomes, thereby releasing PTX into cytoplasm and inhibiting cell proliferation. In vivo studies revealed that TLA/PTX@CS possessed prolonged blood circulation, resulting in elevated tumor accumulation, excellent antitumor efficacy with a tumor inhibition ratio of 75.3%, and significant survival benefit in MCF-7/MDR tumor-bearing mice.
Hence, this TPGS and CS dual-modified lipid-albumin nanosystem provides a promising strategy for targeted delivery of chemotherapeutic drug and reversal of MDR in cancer treatment.
Article information: Kaipei Luo, Feng Xu, Tianyi Yao, Jianping Zhu, Hua Yu, Guangji Wang, Juan Li. TPGS and chondroitin sulfate dual-modified lipid-albumin nanosystem for targeted delivery of chemotherapeutic agent against multidrug-resistant cancer, International Journal of Biological Macromolecules, Volume 183, 2021. https://doi.org/10.1016/j.ijbiomac.2021.05.070.