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Lactoferrin-Modified Gambogic Acid Liposomes for Colorectal Cancer Treatment

Rong WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaJingkun QuSchool of Chinese Materia Medical, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, ChinaXueping TangArtemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510450, ChinaJiaxin ZhangShanghai Institute of Materia MedicaAnte OuShanghai Institute of Materia MedicaQianqian LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaGuihua ChenState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaCaihong ZhengDepartment of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaBahtiyor MuhitdinovInstitute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, 83 M. Ulughbek Street, Tashkent 100125, UzbekistanYongzhuo HuangZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528437, China

Molecular Pharmaceuticsjournal2023en

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Annotatsiya

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.

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Mavzular

Immune cells in cancer Immune Cell Function and Interaction Epigenetics and DNA Methylation

Identifikatorlar

DOI: 10.1021/acs.molpharmaceut.3c00052

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