Prostate-Cancer-Targeted N-(2-Hydroxypropyl)methacrylamide Copolymer/Docetaxel Conjugates

Biodistribution, pharmacokinetics, and efficacy of prostate‐cancer‐targeted HPMA copolymer/DTX conjugates are evaluated in nude mice bearing prostate cancer C4‐2 xenografts. PSMA‐specific monoclonal antibodies 3F/11 are used as the targeting moiety. Control conjugates contain either non‐specific IgG or no IgG. The ratios of tumor accumulation to total background organs (heart, lung, kidney, liver, spleen and blood) accumulation increase substantially with time for the targeted conjugate, and the ratio at 48 h is 7‐fold higher than that at 6 h. Preliminary evaluation of the efficacy of the conjugates in vivo show tumor growth inhibition for all HPMA copolymer/DTX conjugates. HPMA copolymer/DTX/3F/11 antibody conjugates possess binding affinities to PSMA‐expressing prostate cancer C4‐2 cells in the order of 10−9 M. All DTX‐containing conjugates are efficiently cytotoxic with IC50 values of 5–10 × 10−9 M. In vivo experiments on nude mice bearing prostate cancer C4‐2 xenografts demonstrate enhanced tumor accumulation, favorable pharmacokinetics, and tumor growth inhibition.