T regulatory and prostate cancer cell-specific drug targeting using novel XPclad© nanoparticles (42.7)
| Autor: | Rajesh Singh, Shailesh Singh, Praveen K Sharma, James W Lillard, Jr. |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:42.7-42.7 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.42.7 |
| Popis: | In our study, we determined the utility of cisplatin-loaded biodegradable XPclad nanoparticles coated with polycaprolactone-polyethylene glycol copolymers conjugated to folate. We hypothesized that these 28 ± 5 nm sized particles would enhance the therapeutic efficacy of cisplatin through targeted delivery to both prostate tumors and CD4+CD25HiFoxP3+ T cells (Treg) cells. PCa cell lines (PC3 and LNCaP), but not normal prostatic epithelial cells (PrEC and RWPE-1), expressed high levels of folate receptor α (FRα/FR1). Similarly, Treg, but not CD4+CD25LoFoxP3- T cells (T helper), cells expressed FRδ/FR4. Treatment using 20 μM of cisplatin solution resulted in > 90% cell death of PCa cells, PrEC, and RWPE-1 cells as well as purified Treg and T helper cells after 24 hr of culture. However, XPclad nanoparticles, containing cisplatin (equivalent to a 200 nM dose) induced the same level of apoptosis in PCa and Treg cells as cisplatin solution, but did not affect PrEC or RWPE-1 cells or T helper cell death. We also show that PC3 tumor-bearing mice that received either cisplatin solution (8 mg/kg/week) or cisplatin-encapsulated folate-coated XPclad nanoparticles (equivalent cisplatin dose = 0.08 mg/kg/week) had significant tumor regression. While mice receiving cisplatin solution had significant higher kidney and liver toxicities, XPclad nanoparticle-treated mice did not. In conclusion, our studies show that novel XPclad nanoparticles enhance tumor therapy efficacy with lower toxicities and suggest that FR-targeted nanotherapy cause the destruction of prostate tumor cells and Treg cells. |
| Databáze: | OpenAIRE |
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