Hybrid inorganic (nonporous silica)/organic (alginate) core-shell platform for targeting a cisplatin-based Pt(IV) anticancer prodrug

J Inorg Biochem. 2018 Dec:189:185-191. doi: 10.1016/j.jinorgbio.2018.09.019. Epub 2018 Oct 2.

Abstract

Nonporous silica nanoparticles with an external shell containing the 3‑aminopropyl arm (SiNP) were further decorated with alginic acid (SiNP-ALG) as a potential biocompatible delivery system for Pt antitumor agents. Such particles were coupled with the prodrug (OC‑6‑44)‑acetato(β‑alaninato)diamminedichloridoplatinum(IV), 1, through the formation of amide bonds between the pendant carboxylate groups on SiNP-ALG and the free amino group of the complex. Cytosol extracted from tumor cells was able to quickly and efficiently reduce the Pt(IV) prodrug, and produces the active metabolite cisplatin. SiNP-ALG-Pt conjugate was more active than both cisplatin and 1, due to its more efficient cell uptake, whereas the SiNP-ALG unplatinated nanoparticles were deprived of any nonspecific toxicity.

Keywords: Alginic acid; Antiproliferative activity; Platinum(IV); Silica nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cisplatin / chemistry*
  • Cytosol / chemistry
  • Humans
  • Nanoparticles / chemistry*
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*
  • Prodrugs / chemistry*
  • Prodrugs / pharmacology*
  • Silicon Dioxide / chemistry*

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Prodrugs
  • Silicon Dioxide
  • Cisplatin