Biomimetic nano-surfactant stabilizes sub-50 nanometer phospholipid particles enabling high paclitaxel payload and deep tumor penetration

Hoon Choi, Ting Liu, Hui Qiao, Ann Marie Chacko, Shang Hsiu Hu, San-Yuan Chen, Rong Zhou, I. Wei Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Sub-50 nm nanoparticles feature long circulation and deep tumor penetration. However, at high volume fractions needed for intravenous injection, safe, highly biocompatible phospholipids cannot form such nanoparticles due to the fluidity of phospholipid shells. Here we overcome this challenge using a nano-surfactant, a sterilized 18-amino-acid biomimetic of the amphipathic helical motif abundant in HDL-apolipoproteins. As it induces a nanoscale phase (glass) transition in the phospholipid monolayer, the peptide stabilizes 5–7 nm phospholipid micelles that do not fuse at high concentrations but aggregate into stable micellesomes exhibiting size-dependent penetration into tumors. In mice bearing human Her-2-positive breast cancer xenografts, high-payload paclitaxel encapsulated in 25 nm (diameter) micellesomes kills more cancer cells than paclitaxel in standard clinical formulation, as evidenced by the enhanced apparent diffusion coefficient of water determined by in vivo MR imaging. Importantly, the bio-inertness of this biomimetic nano-surfactant spares the nanoparticles from being absorbed by liver hepatocytes, making them more generally available for drug delivery.

Original languageEnglish
Pages (from-to)240-251
Number of pages12
JournalBiomaterials
Volume181
DOIs
StatePublished - 1 Oct 2018

Keywords

  • Amphipathic peptides
  • Apolipoproteins
  • Breast cancer
  • Drug delivery
  • Fluid-gel transition
  • Her-2
  • Lipoproteins
  • Liposomes
  • Micelle
  • Nano medicine
  • Paclitaxel
  • Phospholipid
  • Surfactant

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