Tobacco mosaic virus delivery of phenanthriplatin for cancer therapy

Research output: Contribution to journalArticle

  • External authors:
  • Anna Czapar
  • Yao-Rong Zheng
  • Sourabh Shukla
  • Samuel Awuah
  • Stephen Lippard (Corresponding)
  • Nicole Steinmetz (Corresponding)

Abstract

Phenanthriplatin, cis-[Pt(NH3)2Cl(phenanthridine)](NO3), is a cationic monofunctional DNA-binding platinum(II) anticancer drug candidate with unusual potency and cellular response profiles. Its in vivo efficacy has not yet been demonstrated, highlighting the need for a delivery system. Here we report tobacco mosaic virus (TMV) as a delivery system for phenanthriplatin. TMV forms hollow nanotubes with a polyanionic interior surface; capitalizing on this native structure, we developed a one-step phenanthriplatin loading protocol. Phenanthriplatin release from the carrier is induced in acidic environments. This delivery system, designated PhenPt-TMV, exhibits matched efficacy in a cancer cell panel compared to free phenanthriplatin. In vivo tumor delivery and efficacy were confirmed by using a mouse model of triple negative breast cancer. Tumors treated with PhenPt-TMV were 4× smaller than tumors treated with free phenanthriplatin or cisplatin, owing to increased accumulation of phenanthriplatin within the tumor tissue. The biology-derived TMV delivery system may facilitate translation of phenanthriplatin into the clinic.

Bibliographical metadata

Original languageEnglish
Pages (from-to)4119-4126
JournalACS Nano
Volume10
Issue number4
DOIs
StatePublished - 16 Mar 2016