title: Polymeric nanoparticles for targeted radiosensitization of prostate cancer cells.
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.
authors.affiliation: Department of Bioengineering, The University of Texas at Arlington, Arlington, Texas, 76010; Graduate Program in Biomedical Engineering, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Jyothi U
authors.initials: JU
authors.lastname: Menon
authors.forename: Vasu
authors.initials: V
authors.lastname: Tumati
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D065546:Drug Liberation; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay
chemical_list: C499693:8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one; D002867:Chromones; D009025:Morpholines; D011838:Radiation-Sensitizing Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: NU7441; nanoparticles; prostate cancer; radiosensitization; targeting
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