An injectable nanoparticle generator enhances delivery of cancer therapeutics

Rong Xu, Guodong Zhang, Junhua Mai, Xiaoyong Deng, Victor Segura-Ibarra, Suhong Wu, Jianliang Shen, Haoran Liu, Zhenhua Hu, Lingxiao Chen, Yi Huang, Eugene Koay, Yu Huang, Jun Liu, Joe E. Ensor, Elvin Blanco, Xuewu Liu, Mauro Ferrari, Haifa Shen

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) by means of a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40-50% of treated mice.

Original languageEnglish (US)
Pages (from-to)414-418
Number of pages5
JournalNature Biotechnology
Volume34
Issue number4
Early online dateMar 14 2016
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

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