Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Biol Macromol. 2024 Jun;269(Pt 1):131971. doi: 10.1016/j.ijbiomac.2024.131971. Epub 2024 May 3.
A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.6 % and 55.54 %, respectively. NPs showed a pH and thermoresponsive drug release profile with a sustained prolonged release under physiological conditions. The in vitro cytotoxicity experiments showed a significant synergism of CBP and DOX to induce the IC50 of 1.96 μg/mL in MCF-7 cells and 4.54 μg/mL in MDA-MB-231 cells. Also, the final NPs were safer than free DOX and CBP on normal cells. The in vitro study confirmed the higher potency of the designed NPs in combination therapy against breast cancer cells with lower side effects than free drugs.
一种基于 ZIF-8 壳聚糖-聚（N-异丙基丙烯酰胺）（CS-PNIPAAm）的双 pH/温度敏感核壳纳米制剂被开发用于在乳腺癌细胞中共同递送阿霉素（DOX）和卡铂（CBP）。所得纳米颗粒（NPs）的粒径约为 200nm，zeta 电位约为+30mV。最终 NPs 中的 CBP 和 DOX 载药含量分别为 11.6%和 55.54%。NPs 表现出 pH 和温度响应性药物释放特性，在生理条件下具有持续延长的释放。体外细胞毒性实验表明，CBP 和 DOX 具有显著的协同作用，在 MCF-7 细胞中的 IC50 为 1.96μg/mL，在 MDA-MB-231 细胞中的 IC50 为 4.54μg/mL。此外，最终的 NPs 在正常细胞上比游离的 DOX 和 CBP 更安全。体外研究证实，与游离药物相比，设计的 NPs 在联合治疗乳腺癌细胞方面具有更高的疗效，副作用更低。
