Cationic cellulose nanocrystals complexed with polymeric siRNA for efficient anticancer drug delivery

Carbohydr Polym. 2020 Nov 1:247:116684. doi: 10.1016/j.carbpol.2020.116684. Epub 2020 Jun 25.

Abstract

Surface-modified cellulose nanocrystals (CNCs) were developed for efficient delivery of polymeric siRNA in cancer cells. Cationic CNCs were synthesized using the sequential process of hydrothermal desulfation and chemical modification following which, polymeric siRNA obtained using from a two-step process of rolling circle transcription and Mg2+ chelation was complexed with the modified CNCs by electrostatic interaction. The complexation efficiency was optimized for high drug loading and release in the cytoplasmic environment. The resultant nanocomplex showed significantly enhanced enzymatic stability, gene knockdown efficacy, and apoptosis-induced in vitro therapeutic effect. Our results suggest CNCs as a promising carbohydrate-based delivery platform which could be utilized for RNAi-mediated cancer therapeutics.

Keywords: Cellulose nanocrystals; Hydrothermal desulfation; Nanocomplex; Rolling circle transcription; siRNA delivery.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cations / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cellulose / chemistry*
  • Delayed-Action Preparations / pharmacology*
  • Delayed-Action Preparations / therapeutic use
  • Drug Liberation
  • Gene Knockdown Techniques / methods
  • Humans
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • RNA, Small Interfering / chemical synthesis
  • RNA, Small Interfering / pharmacology*
  • Static Electricity
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Cations
  • Delayed-Action Preparations
  • Polymers
  • RNA, Small Interfering
  • Cellulose