Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours

Suping Li, Yinlong Zhang, Jing Wang, Ying Zhao, Tianjiao Ji, Xiao Zhao, Yanping Ding, Xiaozheng Zhao, Ruifang Zhao, Feng Li, Xiao Yang, Shaoli Liu, Zhaofei Liu, Jianhao Lai, Andrew K. Whittaker, Gregory J. Anderson, Jingyan Wei, Guangjun Nie

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Limited intratumoural perfusion and nanoparticle retention remain major bottlenecks for the delivery of nanoparticle therapeutics into tumours. Here, we show that polymer-lipid-peptide nanoparticles delivering the antiplatelet antibody R300 and the chemotherapeutic agent doxorubicin can locally deplete tumour-associated platelets, thereby enhancing vascular permeability and augmenting the accumulation of the nanoparticles in tumours. R300 is specifically released in the tumour on cleavage of the lipid-peptide shell of the nanoparticles by matrix metalloprotease 2, which is commonly overexpressed in tumour vascular endothelia and stroma, thus facilitating vascular breaches that enhance tumour permeability. We also show that this strategy leads to substantial tumour regression and metastasis inhibition in mice.

Original languageEnglish (US)
Pages (from-to)667-679
Number of pages13
JournalNature Biomedical Engineering
Volume1
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Computer Science Applications

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