HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting

Zhihong Zhang, Juan Chen, Lili Ding, Honglin Jin, Jonathan F. Lovell, Ian R. Corbin, Weiguo Cao, Pui Chi Lo, Mi Yang, Ming Sound Tsao, Qingming Luo, Gang Zheng

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Targeted delivery of intracellular active diagnostics and therapeutics in vivo is a major challenge in cancer nanomedicine. A nanocarrier should possess long circulation time yet be small and stable enough to freely navigate through interstitial space to deliver its cargo to targeted cells. Herein, it is shown that by adding targeting ligands to nanoparticles that mimic high-density lipoprotein (HDL), tumor-targeted sub-30-nm peptide-lipid nanocarriers are created with controllable size, cargo loading, and shielding properties. The size of the nanocarrier is tunable between 10 and 30 nm, which correlates with a pay load of 15-100 molecules of fluorescent dye. Ligand-directed nanocarriers targeting epidermal growth factor receptor (EGFR) are confirmed both in vitro and in vivo. The nanocarriers show favorable circulation time, tumor accumulation and biodistribution with or without the targeting ligand. The EGFR targeting ligand is proved to be essential for the EGFR-mediated tumor cell uptake of the nanocarriers, a prerequisite of intracellular delivery. The results demonstrate that targeted HDL-mimetic nanocarriers are useful delivery vehicles that could open new avenues for the development of clinically viable targeted nanomedicine.

Original languageEnglish (US)
Pages (from-to)430-437
Number of pages8
JournalSmall
Volume6
Issue number3
DOIs
StatePublished - Feb 5 2010

Keywords

  • Cancer therapy
  • Lipids
  • Nanoparticles
  • Peptides
  • Tumor targeting

ASJC Scopus subject areas

  • Engineering (miscellaneous)
  • General Chemistry
  • General Materials Science
  • Biotechnology
  • Biomaterials

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