Bombesin-conjugated nanoparticles improve the cytotoxic efficacy of docetaxel against gastrin-releasing but androgen-independent prostate cancer
Aim: Bombesin (BBN)-conjugated polymeric nanoparticles to target docetaxel (DTX) to prostate cancer cells that overexpress gastrin-releasing peptides receptors. Materials & methods: In vitro cytotoxicity, uptake of nanoparticles and inhibition of cell migration were assessed against human prostate cancer cells. Preclinical pharmacokinetic and tissue-distribution studies of nanoparticles were performed in Balb/c mice and results compared with the marketed formulation Taxotere®. Results: BBN-conjugated DTX-loaded nanoparticles exhibited higher cytotoxicity, inhibition of cell migration and colony formation than non-targeted nanoparticles or DTX alone. More BBN-conjugated nanoparticles were taken up at a faster rate than unconjugated nanoparticles. In vivo, this drug delivery improved pharmacokinetics of DTX by increasing mean residence time and decreasing clearance. Conclusion: This study provides an alternate approach for polysorbate-free delivery of DTX, with improved in vivo performance.
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