Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Mol Pharm. 2023 Aug 7;20(8):3925-3936. doi: 10.1021/acs.molpharmaceut.3c00052. Epub 2023 Jul 28.
Colorectal cancer (CRC) therapy is a big challenge, and seeking an effective and safe drug is a pressing clinical need. Gambogic acid is a potent antineoplastic agent without the drawback of bone marrow suppression. To improve its druggability (e.g., poor water solubility and tumor delivery), a lactoferrin-modified gambogic acid liposomal delivery system (LF-lipo) was developed to enhance the treatment efficacy of CRC. The LF-lipo can specifically bind LRP-1 expressed on colorectal cancer cells to enhance drug delivery to the tumor cells and yield enhanced therapeutic efficacy. The LF-lipo promoted tumor cell apoptosis and autophagy, reduced reactive oxygen species (ROS) levels in tumor cells, and inhibited angiogenesis; moreover, it could also repolarize tumor-associated macrophages from the M2 to M1 phenotype and induce ICD to activate T cells, exhibiting the capability of remodeling the tumor immune microenvironment. The liposomal formulation yielded an efficient and safe treatment outcome and has potential for clinical translation.
结直肠癌（CRC）的治疗是一个巨大的挑战，寻找有效且安全的药物是临床的迫切需求。藤黄酸是一种有效的抗肿瘤药物，没有骨髓抑制的缺点。为了提高其成药性（例如，水溶性差和肿瘤传递），开发了乳铁蛋白修饰的藤黄酸脂质体递药系统（LF-lipo），以增强结直肠癌的治疗效果。LF-lipo 可以特异性结合结直肠癌细胞表面表达的 LRP-1，增强药物向肿瘤细胞的传递，从而提高治疗效果。LF-lipo 促进肿瘤细胞凋亡和自噬，降低肿瘤细胞内活性氧（ROS）水平，抑制血管生成；此外，它还可以将肿瘤相关巨噬细胞从 M2 表型重编程为 M1 表型，并诱导 ICD 激活 T 细胞，表现出重塑肿瘤免疫微环境的能力。这种脂质体制剂产生了高效且安全的治疗效果，具有临床转化的潜力。
