title: Efficacy of polyMPC-DOX prodrugs in 4T1 tumor-bearing mice.
abstract: We report the in vivo efficacy, in tumor-bearing mice, of cancer prodrugs consisting of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) conjugated to doxorubicin (DOX). Our synthesis of polyMPC-DOX conjugates established prodrugs with tunable drug loading, pH sensitive release kinetics, and a maximum tolerated dose in the range of 30-50 mg/kg (DOX equivalent) in healthy mice. Here we show prolonged circulation of polyMPC-DOX, with a measured in vivo half-life (t1/2) 8 times greater than that of the free drug. We observed reduced drug uptake in healthy tissue, and 2-3 times enhanced drug accumulation in tumors for polyMPC-DOX prodrugs compared to free DOX, using BALB/c mice bearing 4T1 tumors. Prolonged survival and reduced tumor growth were observed in mice receiving the polyMPC-DOX prodrug treatment. Moreover, we evaluated immunogenicity of polyMPC-DOX prodrugs by examining complete blood count (CBC) and characteristic cytokine responses, demonstrating no apparent innate or adaptive immune system response.
authors.affiliation: Polymer Science & Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
authors.forename: Samantha
authors.initials: S
authors.lastname: McRae Page
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Henchey
authors.forename: Xiangji
authors.initials: X
authors.lastname: Chen
authors.forename: Sallie
authors.initials: S
authors.lastname: Schneider
authors.forename: Todd
authors.initials: T
authors.lastname: Emrick
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D004317:Doxorubicin / Q000737:chemistry* / Q000627:therapeutic use*; D005260:Female; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D011355:Prodrugs; D004317:Doxorubicin
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