hTERT-molecular targeted therapy of ovarian cancer cells via folate-functionalized PLGA nanoparticles co-loaded with MNPs/siRNA/ wortmannin
hTERT-molecular targeted therapy of ovarian cancer cells via folate-functionalized PLGA nanoparticles co-loaded with MNPs/siRNA/ wortmannin
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DOI：
10.1016/j.lfs.2021.119621
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发表时间：
2021-05-17
期刊：
影响因子：
6.1
通讯作者：
Hemmati, Salar
中科院分区：
文献类型：
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作者：
Ghareghomi, Somayyeh;Ahmadian, Shahin;Hemmati, Salar
有效的端粒酶分子靶向治疗有望成为卵巢癌的有效治疗手段。因此，叶酸功能化的PLGA纳米颗粒（NPs）与hTERT siRNA、作为有效的PI 3 K抑制剂的渥曼青霉素（Wtmn）和作为治疗诊断剂的磁性纳米颗粒（MNP）共负载，以获得用于靶向药物递送以及分子靶向治疗的多功能NPs。采用1HNMR、FTIR、DLS、FE-SEM和TEM等方法对合成的纳米粒子进行了表征。siRNA和Wtmn从双重载药纳米粒的体外释放模式显示早期快速释放，随后持续释放长达200 h。根据MRI分析，通过增加NPs中Fe 3 O 4的浓度，较弱的T2信号强度增强，并且在MRI图像中检测到相当大的对比度。MTT法和中效分析表明，负载Wtmn/siRNA的MNPs-PLGA-F2纳米粒对卵巢癌SKOV-3细胞的杀伤作用最强。负载Wtmn/siRNA的MNPs-PLGA-FA纳米粒较单一药物纳米粒能显著降低hTERT、AKT和p-AKT的表达（P < 0.05）。这些研究结果表明，依赖于组合治疗的多功能纳米颗粒可能具有相当大的潜力，用于有效的端粒酶分子靶向治疗卵巢癌。
Effective telomerase-molecular targeted cancer therapy might be a promising approach for the efficient treatment of ovarian cancer. Therefore, folate-functionalized PLGA nanoparticles (NPs) were co-loaded with hTERT siRNA, Wortmannin (Wtmn), as a potent PI3K inhibitor, and magnetic nanoparticle (MNPs) as a theranostic agent to gain a multifunctional NPs for targeted drug delivery as well as molecular targeted therapy. 1HNMR, FTIR, DLS, FE-SEM and TEM were applied to characterize the synthesized NPs. In vitro discharge pattern for siRNA and Wtmn from the dual drug-loaded NPs showed an early fast release followed by a constant release up to 200 h. According to the MRI analysis, by increasing the concentration of Fe3O4 in NPs, the weaker T2 signal intensity was enhanced, and a considerable contrast was detected in the MRI images. MTT assay and medianeffect analysis showed that the Wtmn/siRNA-loaded MNPs-PLGA-F2 NPs display the most synergistic cytotoxicity on the SKOV-3 ovarian cancer cells. Moreover, the Wtmn/siRNA-loaded MNPs-PLGA-FA NPs could significantly reduce the expression of hTERT, AKT, and p-AKT than the single drug-encapsulated NPs (P < 0.05). Taken together, the findings showed that the multifunctional NPs relying on combinatorial therapy might have considerable potential for effective telomerase-molecular targeted therapy of ovarian cancer.