Co-delivery of doxorubicin and CRISPR/Cas9 or RNAi-expressing plasmid by chitosan-based nanoparticle for cancer therapy

Carbohydr Polym. 2022 Jul 1:287:119315. doi: 10.1016/j.carbpol.2022.119315. Epub 2022 Mar 11.

Abstract

Folic acid (FA) and 2-(Diisopropylamino) ethyl methacrylate (DPA) double grafted trimethyl chitosan (TMC) nanoparticles (FTD NPs) were synthesized for the co-delivery of doxorubicin (DOX) and Survivin CRISPR/Cas9-expressing plasmid (sgSurvivin pDNA) or Survivin shRNA-expressing plasmid (iSur pDNA). FA modification enhanced the uptake of DOX and pDNA loaded into FTD NPs in tumor cells. A rapid release of DOX was triggered under acidic conditions due to pH-sensitiveness of FTD NPs arising from DPA conjugation. Negligible differences between FTD/sgSurvivin pDNA NPs and FTD/iSur pDNA NPs demonstrated that RNA interference (RNAi) and CRISPR/Cas9 technologies possessed comparable antitumor efficiency. Notably, the in vitro and in vivo antitumor efficacies of FTD/DOX/sgSurvivin pDNA NPs were superior to those of single delivery of DOX or sgSurvivin pDNA, while were comparable to those of FTD/DOX/iSur pDNA NPs. These results suggested that the combination of chemotherapeutics and CRISPR/Cas9 systems would provide a potential modality for cancer therapy.

Keywords: CRISPR/Cas9; Chitosan-based nanoparticles; FA modification; RNAi; Synergistic antitumor effects; pH-responsiveness.

MeSH terms

  • CRISPR-Cas Systems / genetics
  • Cell Line, Tumor
  • Chitosan*
  • Doxorubicin / pharmacology
  • Drug Carriers
  • Drug Delivery Systems / methods
  • Folic Acid
  • Frontotemporal Dementia*
  • Humans
  • Nanoparticles*
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Plasmids / genetics
  • RNA Interference
  • Survivin / genetics
  • Survivin / metabolism

Substances

  • Drug Carriers
  • Survivin
  • Doxorubicin
  • Chitosan
  • Folic Acid