Nrp-1 receptor targeting peptide-functionalized TPGS micellar nanosystems to deliver 10-hydroxycampothecin for enhanced cancer chemotherapy

Add time:09/01/2019    Source:sciencedirect.com

Mitochondria are considered the power house of cells where ATP is generated for cellular metabolism, and they also act as a crucial regulator of the intrinsic apoptosis pathway. During ATP synthesis, reactive oxygen species (ROS) are produced as secondary products. Overproduction of ROS can promote mitochondrial DNA mutation, dysfunction and depolarization of the mitochondrial membrane, ultimately resulting in cell death. Therefore, the destruction of mitochondria would be an effective therapeutic approach to kill malignant tumors. Herein, we formulated a PEGylated α-TOS polymeric micellar system loaded with 10-hydroxycamptothecin (HCPT) drug to inhibit the nuclear topoisomerase I enzyme and disrupt the mitochondrial membrane to induce apoptosis. In addition, tumor-penetrating CRGDK peptide-functionalized TPGS2k specifically bound to the Nrp-1 receptor to facilitate higher cell uptake of polymeric micelles by tumor cells. Experimental studies confirmed that HCPT-loaded and peptide-functionalized TPGS2k-TOS micelles (HLPFTTM) showed an enhanced anti-cancer effect in A549 cancer cells.

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