Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery

Diana Dehaini, Ronnie H. Fang, Brian T. Luk, Zhiqing Pang, Che Ming J. Hu, Ashley V. Kroll, Chun Lai Yu, Weiwei Gao, Liangfang Zhang

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Lipid-polymer hybrid nanoparticles, consisting of a polymeric core coated by a layer of lipids, are a class of highly scalable, biodegradable nanocarriers that have shown great promise in drug delivery applications. Here, we demonstrate the facile synthesis of ultra-small, sub-25 nm lipid-polymer hybrid nanoparticles using an adapted nanoprecipitation approach and explore their utility for targeted delivery of a model chemotherapeutic. The fabrication process is first optimized to produce a monodisperse population of particles that are stable under physiological conditions. It is shown that these ultra-small hybrid nanoparticles can be functionalized with a targeting ligand on the surface and loaded with drug inside the polymeric matrix. Further, the in vivo fate of the nanoparticles after intravenous injection is characterized by examining the blood circulation and biodistribution. In a final proof-of-concept study, targeted ultra-small hybrid nanoparticles loaded with the cancer drug docetaxel are used to treat a mouse tumor model and demonstrate improved efficacy compared to a clinically available formulation of the drug. The ability to synthesize a significantly smaller version of the established lipid-polymer hybrid platform can ultimately enhance its applicability across a wider range of applications.

Original languageEnglish
Pages (from-to)14411-14419
Number of pages9
JournalNanoscale
Volume8
Issue number30
DOIs
Publication statusPublished - 2016 Aug 14

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

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