Rakhshani Amir, Maghsoudian Samane, Ejarestaghi Negin Mousavi, Yousefi Mahzad, Yoosefi Sepideh, Asadzadeh Nima, Fatahi Yousef, Darbasizadeh Behzad, Nouri Zeinab, Bahadorikhalili Saeed, Shaabani Alireza, Farhadnejad Hassan, Motasadizadeh Hamidreza
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran university of Medical Sciences, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Int J Biol Macromol. 2025 May;305(Pt 2):141191. doi: 10.1016/j.ijbiomac.2025.141191. Epub 2025 Feb 17.
The main objective of this study was to fabricate a pH-sensitive drug carrier based on coaxial electrospun nanofibrous mats for concurrent local delivery of hydrophilic and hydrophobic anti-cancer drugs to improve the anti-tumor efficacy on breast cancer. Therefore, co-axial electrospinning technique was applied to prepare polyethylene oxide-chitosan/polycaprolactone-chitosan (PEO-CS/PCL-CS) pH-sensitive core-shell nanofibers. Doxorubicin hydrochloride (DOX, hydrophilic anti-cancer) and curcumin (CUR, hydrophobic anticancer) were loaded into core and shell sections of the fabricated pH-sensitive coaxial nanofibers, respectively. Their structure and morphology were analyzed via SEM, TEM, TGA, and FTIR techniques. The results of in vitro release analysis indicated that the release of DOX and CUR from the fabricated nanofibers was strongly depended on pH. The combined effects of the two drugs on MCF-7 cell inhibition, as measured by the MTT assay, revealed that the 1:5 ratio of DOX to CUR resulted in a CI of 0.00492, showing the strongest synergistic effect. The results of in-vivo studies indicated that the PEO-CS-DOX/PCL-CS-CUR pH-sensitive core-shell nanofibers possessed remarkable anti-tumor efficacy. As a result, PEO-CS-DOX/PCL-CS-CUR pH-sensitive core-shell nanofibrous mats with pH-responsive and sustainable and controllable manner could improve the local anti-tumor efficacy on breast cancer via inhibiting the side effects of free DOX and CUR drugs.
本研究的主要目的是制备一种基于同轴电纺纳米纤维垫的pH敏感药物载体，用于同时局部递送亲水性和疏水性抗癌药物，以提高对乳腺癌的抗肿瘤疗效。因此，采用同轴电纺技术制备了聚环氧乙烷-壳聚糖/聚己内酯-壳聚糖（PEO-CS/PCL-CS）pH敏感核壳纳米纤维。将盐酸多柔比星（DOX，亲水性抗癌药物）和姜黄素（CUR，疏水性抗癌药物）分别负载到制备的pH敏感同轴纳米纤维的核部和壳部。通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）、热重分析（TGA）和傅里叶变换红外光谱（FTIR）技术对其结构和形态进行了分析。体外释放分析结果表明，DOX和CUR从制备的纳米纤维中的释放强烈依赖于pH值。通过MTT法测定，两种药物对MCF-7细胞抑制的联合作用表明，DOX与CUR的比例为1:5时，协同指数（CI）为0.00492，显示出最强的协同效应。体内研究结果表明，PEO-CS-DOX/PCL-CS-CUR pH敏感核壳纳米纤维具有显著的抗肿瘤疗效。因此，具有pH响应性且可持续可控的PEO-CS-DOX/PCL-CS-CUR pH敏感核壳纳米纤维垫可以通过抑制游离DOX和CUR药物的副作用来提高对乳腺癌的局部抗肿瘤疗效。
