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.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Czapar
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Yao-Rong
authors.initials: YR
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Imogen A
authors.initials: IA
authors.lastname: Riddell
authors.forename: Sourabh
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Awuah
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D064593:Heterografts; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D010617:Phenanthridines / Q000008:administration & dosage*; D014018:Tissue Distribution; D014027:Tobacco Mosaic Virus / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010617:Phenanthridines; C587603:phenanthriplatin; D002945:Cisplatin
keywords: cancer therapy; drug delivery; metals in medicine; nanotechnology; tobacco mosaic virus