Pt(IV) Prodrugs Designed to Embed in Nanotubes of a Polysaccharide for Drug Delivery

ACS Appl Bio Mater. 2021 Jun 21;4(6):4841-4848. doi: 10.1021/acsabm.1c00128. Epub 2021 Apr 14.

Abstract

Cisplatin exhibits a sufficient killing effect on cancer cells; however, it damages normal cells simultaneously. Herein, we developed a prodrug delivery system based on branched β-(1→3)-d-glucan. This natural biomacromolecule-based polysaccharide nanotube was modified with cisplatin embedded in the hollow cavity (BFCP), showing high anticancer activity and low toxicity in vitro. It is a broad-prospect system, which is based on biocompatible nanomaterials loaded with Pt(IV) prodrugs for cancer cell absorption with subsequent release in tumors by utilizing the intracellular reducibility. BFCP chains adopted a nanotube conformation in water, observed by transmission electron microscopy. In comparison to cisplatin, the Pt(IV) prodrugs not only displayed better antitumor properties but also had significant tumor targeting. A potent natural complex conjugated with redox-responsive platinum prodrugs is a significantly efficient tumor drug demonstrated in vitro and in vivo.

Keywords: anticancer activity; bioactive polysaccharide; drug delivery; platinum(IV) prodrug; reduction-responsive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Apoptosis / drug effects
  • Cell Line
  • Cisplatin / administration & dosage*
  • Cisplatin / chemistry
  • Drug Delivery Systems*
  • Humans
  • Mice
  • Mice, Nude
  • Nanotubes* / chemistry
  • Neoplasms / drug therapy*
  • Polysaccharides / administration & dosage*
  • Polysaccharides / chemistry
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry
  • beta-Glucans / administration & dosage*
  • beta-Glucans / chemistry

Substances

  • Antineoplastic Agents
  • Polysaccharides
  • Prodrugs
  • beta-Glucans
  • Cisplatin