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Advanced Functional Materialsに論文が受理されました。（がん微小環境を支配する間質細胞を二重標的化する新規薬物送達担体の開発）

2021/08/03

Advanced Functional Materialsに論文が受理されました。（がん微小環境を支配する間質細胞を二重標的化する新規薬物送達担体の開発：薬物治療学分野、機能分子構造解析学分野、徳島大学、崇城大学、第一薬科大学との共同研究）

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

Yuki Mizuta, Hitoshi Maeda, Yu Ishima, Yuki Minayoshi, Shota Ichimizu, Ryo Kinoshita, Issay Fujita, Kenshiro Hirata,Teruya Nakamura, Junji Saruwatari, Hidetoshi Arima, Hiroshi Watanabe, Masaki Otagiri and Toru Maruyama

Abstract

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. The authors recently created a mannosylated albumin 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, the authors report on a dual-modified albumin, i.e., mannosylated and polyethylene glycosylated (PEGylated), to improve its blood circulating time and stromal cell-targeting. The product efficiently delivered paclitaxel to stromal cells in a mouse melanoma model, thus resulting in the disruption of stromal cells and suppressed tumor growth, which was seven times stronger than that for PEGylated albumin. The findings suggest that our dual-modified albumin has the potential to provide maximal therapeutic efficacies of chemotherapeutics for the treatment of intractable cancer.

Statement of significance

In the present study, we successfully designed and developed a monoPEG40k-Man-HSA that enables the dual-targeting of TAM and CAF, both of which mainly govern the tumor microenvironment. The findings of the current study not only reveal that the monoPEG40k-Man-HSA is a promising carrier for the treatment of types of intractable cancers, but also suggest the usefulness of the novel strategy of the dual-targeting to cancer-specific mannose receptors.