The programmed site-specific delivery of the angiostatin sunitinib and chemotherapeutic paclitaxel for highly efficient tumor treatment

Jin He, Hong Xiao, Bo Li, Yuan Peng, Xiaoxia Li, Yong Wang, Grazyna Adamus, Marek Kowalczuk, Xintao Shuai

Research output: Contribution to journalArticle

Abstract

Malignant solid tumors are composed of tumor cells, stromal cells and the complex networks of the tumor microenvironment (TME), which is the underlying cause of the unsatisfactory outcome of conventional chemotherapy approaches only aimed at cancer cell killing. In this study, a novel TME-responsive polymeric micelle has been developed for the programmed site-specific delivery of the angiostatin sunitinib and chemotherapeutic paclitaxel (PTX). The pH-sensitive micelle core encapsulates PTX, while β-cyclodextrin molecules being conjugated to the micelle shell via matrix metalloproteinase 2 (MMP-2) sensitive peptides include sunitinib. Following the pH and MMP-2 dual sensitive structure design, the micelle may sequentially release sunitinib inside the tumor extracellular matrix and PTX into cancer cells through responding to enriched MMP-2 levels and decreased pH, respectively. Consequently, the anti-angiogenesis effect of sunitinib and tumor cell-killing effect of PTX synergize, resulting in highly efficient tumor treatment.

Original languageEnglish (US)
Pages (from-to)4953-4962
Number of pages10
JournalJournal of Materials Chemistry B
Volume7
Issue number32
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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