Lung cancer chemotherapy using nanoparticles: Enhanced target ability of redox-responsive and pH-sensitive cisplatin prodrug and paclitaxel

Biomed Pharmacother. 2021 Apr:136:111249. doi: 10.1016/j.biopha.2021.111249. Epub 2021 Jan 12.

Abstract

Platinum-based combination therapy is more effective and less toxic, but lack of targeting, and is not capable to enrich in the tumor zone. To obstacle these drawbacks, prodrug and nanotechnology strategies have been investigated in this study. GSH-responsive and pH-responsive cisplatin prodrug was synthesized. Cisplatin prodrug and paclitaxel co-loaded nanoparticles: DDP-P/PTX NPs were constructed. The drug release behavior and cytotoxicity of nanoparticles was assessed in vitro. In vivo anticancer efficiency and toxicity were evaluated on lung cancer bearing mice animal model. DDP-P/PTX NPs had a nanoscale size of 112.9 ± 3.5 nm. A reduction and pH triggered drug release with a synergistic tumor cell inhibition ability was observed by DDP-P/PTX NPs. DDP-P/PTX NPs also exhibited high tumor distribution, low systemic toxicity and remarkable antitumor effects in vivo. DDP-P/PTX NPs could be applied as promising anticancer system for the treatment of NSCLC.

Keywords: Cisplatin prodrug; Lung cancer; Nanoparticles; Paclitaxel; Redox-responsive; pH-sensitive.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology*
  • Cisplatin / toxicity
  • Drug Compounding
  • Drug Liberation
  • Female
  • Glutathione / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles*
  • Nanotechnology
  • Oxidation-Reduction
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology*
  • Paclitaxel / toxicity
  • Tissue Distribution
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Glutathione
  • Paclitaxel
  • Cisplatin