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A novel αVβ3 ligand-modified HPMA copolymers for anticancer drug delivery

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journal contribution
posted on 2017-08-18, 08:47 authored by Fengling Wang, Lian Li, Wei Sun, Lijia Li, Yuanyuan Liu, Yuan Huang, Zhou Zhou

The integrin αVβ3 receptor emerged as one of the most promising targets owing to its high expression on the surface of various malignant tumour cells and tumour angiogenesis endothelial cells, but with little expression in mature endothelial cells and the majority of normal cells. Here, we report a new targeting ligand FQSIYPpIK (FQS) with high affinity to integrin αVβ3 receptor. To take the advantage of the particular interaction between FQS and integrin αVβ3 receptor, FQS was linked to N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. A model drug doxorubicin (DOX) was simultaneously conjugated to the same HPMA copolymers via pH-sensitive hydrazone linkages (FQS–HPMA–DOX). In in vitro study, FQS–HPMA–DOX could be internalised into αVβ3 receptor-overexpressed B16F10 cells via a highly specific ligand − receptor pathway (5.0 times and 4.5 times higher cellular internalisation than HPMA–DOX and a scrambled peptide (s)-FQS (sequence: SYFIPKQIp)-modified copolymers ((s)-FQS–HPMA–DOX)). It is worth noting that compared with the classical αVβ3 ligand cRGDfK-modified HPMA copolymers (cRGDfK–HPMA–DOX), FQS–HPMA–DOX also showed superior targeting efficiency. In in vivo study in the B16F10 melanoma bearing mice model showed the antitumour efficiency of FQS–HPMA–DOX (83.9%) were significantly higher than HPMA–DOX (44.9%) and cRGDfK–HPMA–DOX (77.5%). These results suggest that FQS peptide can act as an effective targeting ligand for the delivery of therapeutic agents.


National Natural Science Foundation of China10.13039/501100001809