Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Nanomedicine (Lond). 2021 Feb;16(5):355-372. doi: 10.2217/nnm-2020-0453. Epub 2021 Feb 16.
The aim of this study was to prepare small-molecule camptothecin (CPT) prodrugs and evaluate their effectiveness in colorectal carcinoma therapy. Prodrug nanoparticles (NPs) were physicochemically characterized and evaluated for their cytotoxicity in human colon cancer (HCT116) cell lines. The antitumor efficacy of the NPs was evaluated in HCT116 tumor-bearing mice. The prepared NPs exhibited high drug loading capacity (32% of CPT w/w) and also kept a high active lactone fraction of CPT (>85%) during circulation. The NPs were internalized into tumor cells efficiently compared with free drug and significantly enhanced the drug's therapeutic efficacy. The developed small-molecule CPT prodrug NPs could be a promising strategy in the clinical therapy of colorectal carcinoma.
本研究旨在制备小分子喜树碱（CPT）前药，并评估其在结直肠癌治疗中的疗效。前药纳米颗粒（NPs）进行了物理化学表征，并在人结肠癌细胞系（HCT116）中评估了其细胞毒性。在 HCT116 荷瘤小鼠中评价了 NPs 的抗肿瘤疗效。所制备的 NPs 表现出高载药量（CPT 重量的 32%），并且在循环过程中也保持了高比例的活性内酯形式的 CPT（>85%）。与游离药物相比，NPs 能有效地被肿瘤细胞内化，并显著增强了药物的治疗效果。开发的小分子 CPT 前药 NPs 可能是结直肠癌临床治疗的一种有前途的策略。
