Tobacco Mosaic Virus Delivery of Phenanthriplatin for Cancer therapy

Anna E. Czapar, Yao Rong Zheng, Imogen A. Riddell, Sourabh Shukla, Samuel G. Awuah, Stephen J. Lippard, Nicole F. Steinmetz

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

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.

Original languageEnglish
Pages (from-to)4119-4126
Number of pages8
JournalACS Nano
Volume10
Issue number4
DOIs
StatePublished - Apr 26 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Keywords

  • cancer therapy
  • drug delivery
  • metals in medicine
  • nanotechnology
  • tobacco mosaic virus

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

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