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A Mannosylated, PEGylated Albumin as a Drug Delivery System for the Treatment of Cancer Stroma Cells

机译：甘露糖基化的聚乙二醇化白蛋白作为治疗癌基质细胞的药物递送系统

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摘要

Mannose receptors that are expressed on macrophages and fibroblasts in cancer stroma are promising therapeutic targets for cancer treatment. Albumin can be used as a drug carrier in chemotherapeutics due to its accumulation in the tumor tissue by the enhanced permeability and retention effects. A mannosylated albumin was recently developed as a new drug carrier targeting cells that express mannose receptors such as macrophages and fibroblasts in cancer stroma. The mannosylated albumin is specifically distributed to hepatic macrophages in vivo, leading to an extremely short residence time in the blood. Here, a dual-modified albumin, i.e., mannosylated and polyethylene glycosylated (PEGylated) is reported, to improve its blood circulating time and stromal cell targeting. The product efficiently delivers paclitaxel to stromal cells in a mouse melanoma model, thus resulting in the disruption of stromal cells and suppressed tumor growth, which is seven times stronger than that for PEGylated albumin. The findings suggest that the dual-modified albumin has the potential to provide maximal therapeutic efficacies of chemotherapeutics for the treatment of intractable cancer.
机译：在巨噬细胞和癌基质中的成纤维细胞表达的甘露糖受体是癌症治疗的治疗靶标。白蛋白可以在化学治疗剂中用作药物载体，由于其在肿瘤组织中积累通过增强的渗透性和保留效应。最近甘露糖基化白蛋白是作为一种新的药物载体靶向细胞，其表达甘露糖受体如癌基质中的巨噬细胞和成纤维细胞。甘露糖苷化白蛋白特异性分布到体内肝巨噬细胞，导致血液中的极短停留时间。这里，据报道，双改性白蛋白，即甘露糖基化和聚乙二醇基化（聚乙二醇化），以改善其血液循环时间和基质细胞靶向。该产品有效地将紫杉醇递到小鼠黑素瘤模型中的基质细胞，从而导致基质细胞的破坏并抑制肿瘤生长，这比聚乙二醇化白蛋白更强的七倍。研究结果表明，双改性白蛋白有可能为治疗顽固性癌症提供最大的化学治疗方法。

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  • 来源
    《Advanced Functional Materials》 |2021年第43期|2104136.1-2104136.17|共17页
  • 作者

    Mizuta Yuki; Maeda Hitoshi; Ishima Yu; Minayoshi Yuki; Ichimizu Shota; Kinoshita Ryo; Fujita Issei; Kai Takuma; Hirata Kenshiro; Nakamura Teruya; Saruwatari Junji; Arima Hidetoshi; Watanabe Hiroshi; Otagiri Masaki; Maruyama Toru;

  • 作者单位

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Tokushima Univ Dept Pharmacokinet & Biopharmaceut Inst Biomed Sci 1-78-1 Sho Machi Tokushima 7708505 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Sojo Univ Fac Pharmaceut Sci 4-22-1 Ikeda Kumamoto 8600082 Japan;

    Kumamoto Univ Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oehonmachi Kumamoto 8620973 Japan;

    Kumamoto Univ Grad Sch Pharmaceut Sci Div Pharmacol & Therapeut Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Daiichi Univ Pharm Lab Evidence Based Pharmacotherapy Minami Ku 22-1 Tamagawa Machi Fukuoka 8158511 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

    Sojo Univ Fac Pharmaceut Sci 4-22-1 Ikeda Kumamoto 8600082 Japan;

    Kumamoto Univ Dept Biopharmaceut Grad Sch Pharmaceut Sci Chuo Ku 5-1 Oe Honmachi Kumamoto 8620973 Japan;

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  • 正文语种 eng
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  • 关键词

    cancer-associated fibroblasts; drug delivery systems; human serum albumin; mannose receptors; mannosylation; polyethylene glycosylation; tumor-associated macrophages;

    机译：癌症相关的成纤维细胞;药物递送系统;人血清白蛋白;甘露糖受体;甘露那糖化;聚乙烯糖基化;肿瘤相关的巨噬细胞;

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