Polymeric nanoparticles for targeted radiosensitization of prostate cancer cells

One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle (NP) system consisting of poly (lactic‐co‐glycolic acid) (PLGA) NPs conjugated with prostate cancer cell penetrating peptide‐R11 and encapsulated with a potent radio‐sensitizer 8‐dibenzothiophen‐4‐yl‐2‐morpholin‐4‐yl‐chromen‐4‐one (NU7441) to allow prostate cancer‐specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11‐conjugated NPs (R11‐NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in deionized water and serum. The NPs were cytocompatible with immortalized prostate cells (PZ‐HPV‐7). Further, the particles showed a bi‐phasic release of encapsulated NU7441 and were taken up by PC3 prostate cancer cells in a dose‐ and magnetic field‐dependent manner while not being taken up in nonprostate cancer cell lines. In addition, R11‐NU7441 NPs were effective radiation sensitizers of prostate cancer cell lines in vitro. These results thus demonstrate the potential of R11‐conjugated PLGA NPs as novel platforms for targeted radiosensitization of prostate cancer cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1632–1639, 2015.