Multistage Continuous Targeting with Quantitatively Controlled Peptides on Chitosan-Lipid Nanoparticles with Multicore–Shell Nanoarchitecture for Enhanced Orally Administrated Anticancer In Vitro and In Vivo

Chia Wei Su, Ching Shu Yen, Chih Sheng Chiang, Chin Hao Hsu, San-Yuan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A DOX-loaded polysaccharide-lecithin reverse micelles triglyceride-based oral delivery nanocarrier (D-PL/TG NPs) conjugated with (i) RGD peptide for targeting to β1 integrin of M cells and (ii) Lyp-1 peptide for targeting to the p32 receptor of MDA-MB-231 cells is used to investigate the multistage continuous targeting capabilities of these peptide-conjugated nanocarriers (GLD-PL/TG NPs) for tumor therapy. Variations in the targeting efficacy and pharmacokinetic properties are investigated by quantitatively controlling the surface density of different peptides on the nanoparticles. In vitro permeability in a human follicle-associated epithelium model and cytotoxicity against MDA-MB-231 cells indicate that the nanocarriers conjugated with high RGD peptide concentrations display a higher permeability due to the existence of M cells with higher transcytosis activity, but a higher concentration of conjugated Lyp-1 peptide exhibits the lowest cell viability. Being benefited from specific targeting of peptide conjugation, improved bioavailability and enhanced tumor accumulation are achieved by the GLD-PL/TG NPs, leading to better antitumor efficacy. The results of in vivo biodistribution and antitumor studies reveal that the effect of LyP-1 peptide is more predominant than that of RGD peptide. This proof of multistage continuous targeting may open the door to a new generation of oral drug delivery systems in targeted cancer therapy. (Figure presented.).

Original languageEnglish
Article number1600260
JournalMacromolecular Bioscience
Volume17
Issue number2
DOIs
StatePublished - 1 Feb 2017

Keywords

  • Drug targeting
  • Lyp-1
  • Multistage continuous targeting delivery
  • Oral Administration
  • RGD

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