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

doi:10.1021/acsnano.5b07360

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 journal › Article › peer-review

153 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 language	English
Pages (from-to)	4119-4126
Number of pages	8
Journal	ACS Nano
Volume	10
Issue number	4
DOIs	https://doi.org/10.1021/acsnano.5b07360
State	Published - Apr 26 2016

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

Funding

This work was supported in part by grants from the National Cancer Institute (CA 034992 to S.J.L.), National Science Foundation (CHE 1306447 to N.F.S.), and Mt. Sinai Foundation (to N.F.S.). A.E.C. was supported in part by NIH grants T32 GM007250 and TL1 TR000441.

Funders	Funder number
National Science Foundation Arctic Social Science Program	CHE 1306447
National Institutes of Health (NIH)	T32 GM007250, TL1 TR000441
National Childhood Cancer Registry – National Cancer Institute	R37CA034992
Mt. Sinai Health Care Foundation

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.5b07360

Cite this

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title = "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.",

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author = "Czapar, \{Anna E.\} and Zheng, \{Yao Rong\} and Riddell, \{Imogen A.\} and Sourabh Shukla and Awuah, \{Samuel G.\} and Lippard, \{Stephen J.\} and Steinmetz, \{Nicole F.\}",

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AU - Zheng, Yao Rong

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AU - Shukla, Sourabh

AU - Awuah, Samuel G.

AU - Lippard, Stephen J.

AU - Steinmetz, Nicole F.

PY - 2016/4/26

Y1 - 2016/4/26

N2 - 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.

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Tobacco Mosaic Virus Delivery of Phenanthriplatin for Cancer therapy

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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