Tobacco Mosaic Virus Delivery of Phenanthriplatin for Cancer therapy.

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.

• Authors: Anna E Czapar, Yao-Rong Zheng, Imogen A Riddell, Sourabh Shukla, Samuel G Awuah, Stephen J Lippard, Nicole F Steinmetz
• Journal: ACS nano (ACS Nano) Vol. 10 Issue 4 Pg. 4119-26 (04 26 2016) ISSN: 1936-086X [Electronic] United States
• PMID: 26982250 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Phenanthridines
• phenanthriplatin
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line, Tumor
• Cell Survival
• Cisplatin (administration & dosage)
• Drug Delivery Systems
• Heterografts
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Organoplatinum Compounds (administration & dosage)
• Phenanthridines (administration & dosage)
• Tissue Distribution
• Tobacco Mosaic Virus (genetics)
• Triple Negative Breast Neoplasms