Byeon, Yeongseon Lee, Jeong-Won Choi, Whan Soo Won, Ji Eun Kim, Ga Hee Kim, Min Gi Wi, Tae In Lee, Jae Myeong Kang, Tae Heung Jung, In Duk Cho, Young-Jae Ahn, Hyung Jun Shin, Byung Cheol Lee, Young Joo Sood, Anil K. Han, Hee Dong Park, Yeong-Min 2024-01-19T21:31:20Z 2024-01-19T21:31:20Z 2021-09-05 2018-11-01 0008-5472 https://pubs.kist.re.kr/handle/201004/120705 Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP were 220 nm and -7.3 mV, respectively. Incorporation efficiencies for PTX and FAK siRNA in the HA-PLGA-NPs were 77% and 85%, respectively. HA-PLGA-NP showed higher binding efficiency for CD44-positive tumor cells as compared with CD44- negative cells. HA-PLGA (PTX+FAK siRNA)-NP caused increased cytotoxicity and apoptosis in drug-resistant tumor cells. Treatment of human epithelial ovarian cancer tumor models HeyA8-MDR (P < 0.001) and SKOV3-TR (P < 0.001) with HA-PLGA (PTX+FAK siRNA)-NP resulted in significant inhibition of tumor growth. Moreover, in a drug-resistant, patient-derived xenograft (PDX) model, HA-PLGA (PTX+FAK siRNA)-NP significantly inhibited tumor growth compared with PTX alone (P < 0.002). Taken together, HA-PLGA-NP acts as an effective and selective delivery system for both the chemotherapeutic and the siRNA in order to overcome chemoresistance in ovarian carcinoma. Significance: These findings demonstrate the efficacy of a novel, selective, two-in-one delivery system to overcome chemoresistance in epithelial ovarian cancer. (C) 2018 AACR. English AMER ASSOC CANCER RESEARCH FOCAL-ADHESION KINASE RESISTANCE CISPLATIN ANGIOGENESIS ACTIVATION DELIVERY THERAPY GROWTH ACID CD44-Targeting PLGA Nanoparticles Incorporating Paclitaxel and FAK siRNA Overcome Chemoresistance in Epithelial Ovarian Cancer Article 10.1158/0008-5472.CAN-17-3871 1 CANCER RESEARCH, v.78, no.21, pp.6247 - 6256 CANCER RESEARCH 78 21 6247 6256 scie scopus 000448929300019 2-s2.0-85055907384 Oncology Oncology Article FOCAL-ADHESION KINASE RESISTANCE CISPLATIN ANGIOGENESIS ACTIVATION DELIVERY THERAPY GROWTH ACID siRNA chemoresistance drug delivery cancer