A biocompatible glycol-capped nano-delivery system with stimuli-responsive drug release kinetics abrogates cancer cell survival

Int J Biol Macromol. 2020 Dec 15;165(Pt A):568-581. doi: 10.1016/j.ijbiomac.2020.09.121. Epub 2020 Sep 20.

Abstract

An eco-friendly polysaccharide (PSP001) isolated from the fruit rind of Punica granatum is a biodegradable polymer with immunostimulatory and anticancer properties. PSP001 was employed for the stimuli-responsive targeted delivery of antineoplastic agent doxorubicin (Dox) by the fabrication of Dox-holding PSP nanoparticles (DPN). The galactose moieties of PSP001 were occupied as an effective tumor-targeted motif against the over-expressed asialoglycoprotein and galectin receptors of cancers. DPN followed a pH-sensitive cargo release kinetics, competent cancer cell internalization profile, and appealing biocompatibility towards peripheral red blood cells. The selective execution of caspase-mediated programmed cell death by the DPN on cancer cells was confirmed with multiple apoptosis studies. Extensive toxicity profiling on BALB/c mice rules out any palpable signs of abnormality with DPN administration while bare Dox produced vital signs of toxicity. Studies on syngraft solid tumor-bearing mice uncovered the tumor homing nature of DPN with the subsequent release of the entrapped drug which further translated in the direction of a significant reduction in the tumor payload and enhanced survival benefits, thus offering a robust approach towards endurable cancer management.

Keywords: Doxorubicin; Drug delivery; Polysaccharide; Tumor reduction; pH.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacokinetics
  • Antineoplastic Agents* / pharmacology
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Doxorubicin