title: Doxorubicin-conjugated polypeptide nanoparticles inhibit metastasis in two murine models of carcinoma.
abstract: Drug delivery vehicles are often assessed for their ability to control primary tumor growth, but the outcome of cancer treatment depends on controlling or inhibiting metastasis. Therefore, we studied the efficacy of our genetically encoded polypeptide nanoparticle for doxorubicin delivery (CP-Dox) in the syngeneic metastatic murine models 4T1 and Lewis lung carcinoma. We found that our nanoparticle formulation increased the half-life, maximum tolerated dose, and tumor accumulation of doxorubicin. When drug treatment was combined with primary tumor resection, greater than 60% of the mice were cured in both the 4T1 and Lewis lung carcinoma models compared to 20% treated with free drug. Mechanistic studies suggest that metastasis inhibition and survival increase were achieved by preventing the dissemination of viable tumor cells from the primary tumor.
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
authors: Eric M
authors: EM
authors: Mastria
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
authors: Mingnan
authors: M
authors: Chen
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
authors: Jonathan R
authors: JR
authors: McDaniel
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
authors: Xinghai
authors: X
authors: Li
authors: Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jinho
authors: J
authors: Hyun
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States; Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27708, United States.
authors: Mark W
authors: MW
authors: Dewhirst
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States; Center for Biologically Inspired Materials and Materials Systems, Duke University, Durham, NC 27708, United States. Electronic address: chilkoti@duke.edu.
authors: Ashutosh
authors: A
authors: Chilkoti
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006207:Half-Life; D020714:Maximum Tolerated Dose; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry*; D016019:Survival Analysis; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D010455:Peptides; D004317:Doxorubicin
keywords: Cancer; Delivery vehicle; Doxorubicin; Metastasis; Nanoparticle; Recombinant polypeptide
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