Synthetic polymer material modified by d-peptide and its targeted application in the treatment of non-small cell lung cancer

Int J Pharm. 2022 May 10:619:121651. doi: 10.1016/j.ijpharm.2022.121651. Epub 2022 Mar 11.

Abstract

Liposomes functionalized with targeted material offer a breakthrough compared with passive drug delivery. Here, we designed a polymer material, VAP-PEG3350-DSPE (VAP-PEG-DSPE), modified with a d-peptide VAP ligand that combines tumor-homing VAP with GRP78 receptor, a cancer marker on the membranes of many cancer cells. This paper establishes a docetaxel-loaded lipid nanodisk modified with multifunctional material to evaluate its anti-NSCLC efficacy in vivo. Additionally, the present study verified that VAP-conjugated nanodisks adapt to the developed tumor vasculature of the lung cancer microenvironment, making it a promising nanocarrier for NSCLC-targeting therapy. Moreover, in vitro and in vivo experiments demonstrated the targeting ability of VAP-DISK/DTX to tumor cells. Lung slices of mice also demonstrated the safety of VAP-DISK/DTX. The encapsulation efficiency of docetaxel-disks (VAP-DISK/DTX) was as high as 92.46±4.48%. Encapsulating anti-cancer drugs in lipid nanoparticles is thus an effective mechanism to change the pharmacokinetic and pharmacodynamic characteristics of drugs.

Keywords: Active targeting material; Drug delivery; Lipid nanodisk; NSCLC; VAP.

MeSH terms

  • Animals
  • Antineoplastic Agents*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Cell Line, Tumor
  • Docetaxel / pharmacology
  • Drug Delivery Systems
  • Liposomes
  • Lung Neoplasms* / drug therapy
  • Mice
  • Mice, Nude
  • Nanoparticles*
  • Peptides
  • Polymers
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Lipid Nanoparticles
  • Liposomes
  • Peptides
  • Polymers
  • Docetaxel