چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for the delivery of JSI-124 (a small molecule inhibitor of STAT3) to tumor and immunosuppressed DCs using poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs). For this purpose, JSI-124 was chemically conjugated to PLGA and the PLGA-JSI-124 conjugate was formulated into nanoparticles using the emulsification solvent evaporation method. The attachment of JSI-124 to PLGA was confirmed by a combination of thin layer chromatography and (1)H NMR. The level of JSI-124 in NPs, determined by liquid chromatography-mass spectrometry, was found to be 1.7 +/- 0.3 microg per mg of PLGA. The PLGA-JSI-124 NPs demonstrated a controlled drug release profile over a 1-month period and exhibited potent anticancer and STAT3 inhibitory activity comparable to the soluble JSI-124 after 24 h incubation with B16 melanoma cells, in vitro. Moreover, PLGA-JSI-124 NPs efficiently suppressed the level of p-STAT3 in p-STAT3(high) DCs, generated from mouse bone marrow cells in the presence of conditioned media of B16 cells (B16CM-DCs), and improved their function as assessed by mixed lymphocyte reaction (MLR). Specifically cotreatment of B16CM-DCs with PLGA-JSI-124 NPs and PLGA NPs containing the DC adjuvant CpG resulted in higher levels of T cell proliferation in the MLR assay compared with B16CM-DCs untreated or treated with either CpG NPs or JSI-124 NPs alone. Our results indicate that PLGA NPs containing conjugated JSI-124 can potentially provide a useful platform for sustained JSI-124 release in tumor and its targeted delivery to DCs leading to the modulation of anticancer response by JSI-124 in tumor cells and immunosuppressed DCs, in vitro. |
| نویسنده | نفر چندم مقاله |
|---|---|
| ام لیلا مولوی | اول |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| molavi et al ACS 2010.pdf | 1397/08/20 | 356083 | دانلود |
