Li Weinan, Gong HeXin, Fu Yuhan, Sun Jialin, Wang Yanhong
School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, People's Republic of China; Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, People's Republic of China.
Biological Science and Technology Department, Heilongjiang Vocational College for Nationalities, Harbin 150066, People's Republic of China.
Colloids Surf B Biointerfaces. 2022 Nov;219:112838. doi: 10.1016/j.colsurfb.2022.112838. Epub 2022 Sep 14.
Developing chemotherapy with nanoparticle-based prodrugs provides promising strategies for improving the safety and delivery of anti-cancer drugs therapeutics and effective cancer treatment. Herein, we developed a pH-sensitive prodrug delivery system (All-Trans-Retinoic Acid (ATRA) grafted poly (β-amino esters) (PBAE) copolymers, ATRA-g-PBAE) for delivery of ATRA with some physicochemical and biological properties. The in vitro release of ATRA-g-PBAE prodrug nanoparticles (PNPs) was sustained-release and pH-sensitive. The cytotoxicity and uptake of different preparations in vitro were evaluated on MCF-7 cells at pH 7.4 and 5.5. The carrier PBAE had no cytotoxicity, and ATRA-g-PBAE PNPs could significantly inhibit cell growth at pH 5.5. MCF-7 cells treated with Cy5.5 grafted PBAE (Cy5.5-PBAE) showed stronger fluorescence signals at pH 5.5. Meanwhile, ATRA-g-PBAE PNPs entered the cell via a clathrin-mediated endocytic pathway. Subsequently, PBAE protonation facilitated the escape of PNPs from the lysosome and released the drug. ATRA-g-PBAE seems promising as a novel pH-sensitive prodrug to overcome the limitations of ATRA for breast cancer therapy.
开发基于纳米颗粒的前药化疗方法为提高抗癌药物治疗的安全性、递送效率及有效治疗癌症提供了有前景的策略。在此，我们开发了一种pH敏感的前药递送系统（全反式维甲酸（ATRA）接枝聚（β-氨基酯）（PBAE）共聚物，ATRA-g-PBAE），用于递送具有某些物理化学和生物学特性的ATRA。ATRA-g-PBAE前药纳米颗粒（PNPs）的体外释放具有缓释性且对pH敏感。在pH 7.4和5.5条件下，对MCF-7细胞评估了不同制剂的体外细胞毒性和摄取情况。载体PBAE无细胞毒性，且ATRA-g-PBAE PNPs在pH 5.5时可显著抑制细胞生长。用Cy5.5接枝PBAE（Cy5.5-PBAE）处理的MCF-7细胞在pH 5.5时显示出更强的荧光信号。同时，ATRA-g-PBAE PNPs通过网格蛋白介导的内吞途径进入细胞。随后，PBAE质子化促进了PNPs从溶酶体中逃逸并释放药物。作为一种新型的pH敏感前药，ATRA-g-PBAE似乎有望克服ATRA在乳腺癌治疗中的局限性。
