title: Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis.
abstract: Peritoneal metastasis is a major cause of morbidity and mortality in ovarian cancer. While intraperitoneal chemotherapy and radiotherapy have shown favorable clinical results, both are limited by their non-targeted nature. We aimed to develop a biologically targeted nanoparticle therapeutic for the treatment of ovarian cancer peritoneal metastasis. Folate-targeted nanoparticles encapsulating chemotherapy and/or radiotherapy were engineered. Paclitaxel (Ptxl) was used as the chemotherapeutic and yittrium-90 ((90)Y) was employed as the therapeutic radioisotope. Folate was utilized as the targeting ligand as most ovarian cancers overexpress the folate receptor. Nanoparticle characterization studies showed monodispersed particles with controlled Ptxl release. Folate targeting ligand mediated the uptake of NPs into tumor cells. In vitro efficacy studies demonstrated folate-targeted NPs containing chemoradiotherapy was the most effective therapeutic compared to folate-targeted NPs containing a single therapeutic or any non-targeted NP therapeutics. In vivo efficacy studies using an ovarian peritoneal metastasis model showed that folate-targeted NP therapeutics were significantly more effective than non-targeted NP therapeutics. Among the folate-targeted therapeutics, the NP containing chemoradiotherapy appeared to be the most effective. Our results suggest that folate-targeted nanoparticles containing chemoradiotherapy have the potential as a treatment for ovarian peritoneal metastasis.
authors.affiliation: Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Werner
authors.forename: Shrirang
authors.initials: S
authors.lastname: Karve
authors.forename: Rohit
authors.initials: R
authors.lastname: Sukumar
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Cummings
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Copp
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Chen
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015153:Blotting, Western; D003131:Combined Modality Therapy; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005492:Folic Acid; D017239:Paclitaxel