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

Int J Pharm

Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Published: August 2018

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 TPGS 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 TPGS-TOS micelles (HLPFTTM) showed an enhanced anti-cancer effect in A549 cancer cells.

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http://dx.doi.org/10.1016/j.ijpharm.2018.05.074DOI Listing

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