Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1632-1639 |
Number of pages | 8 |
Journal | Journal of Biomedical Materials Research - Part A |
Volume | 103 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2015 |
Keywords
- NU7441
- nanoparticles
- prostate cancer
- radiosensitization
- targeting
ASJC Scopus subject areas
- Ceramics and Composites
- Biomaterials
- Biomedical Engineering
- Metals and Alloys