Metastasis is the major cause of high mortality in cancer patients, thus metastasis suppression is the key and most challenging mission in cancer therapies. Many patients have generated micro-metastasis at the early stage, whereas conventional therapeutic methods or drugs are far less effective against metastasis. Therefore, it is necessary to identify vital mechanisms in process of metastasis formation for the development of novel and efficient strategies for metastasis inhibition.

Pre-metastatic niche, a specific inflammatory microenvironment, allows the colonization of circulating tumor cells (CTCs) and serves as a potential target for metastasis suppression. However, little effort has been dedicated to developing drug delivery systems to modulate the pre-metastatic microenvironment. Professor Jun Chen’s group from School of Pharmacy of Fudan University and Professor Xiaoling Gao’s team from Shanghai Jiao Tong University collaborated to report a targeted hybrid micelle for pre-metastatic niche modulation and metastasis inhibition. The micelles are self-assembled with the oleate carbon chain derivative of metformin and docosahexaenoic acid (DHA), two anti-inflammatory agents with low toxicity, and coated with fucoidan for pre-metastatic niche targeting. The functionalized micelles (FucOMDs) exhibit excellent blood circulation profile and targeting effect to the pre-metastatic niche, inhibit CTC adhesion to activated endothelial cells, alleviate lung vascular permeability and reverse the aberrant expression of key marker proteins in pre-metastatic niches. Consequently, FucOMDs prevent metastasis formation effectively, and suppress both primary tumor growth and metastasis establishment when combined with targeted chemotherapy. Collectively, this study provides proof of concept that the modulation of pre-metastatic niche with targeted anti-inflammatory agents offers a powerful strategy and a safe and clinical translational method for metastasis suppression in cancer therapies.

Relevant studies were published online in Nano Letters entitled “Metformin and Docosahexaenoic Acid Hybrid Micelles for Premetastatic Niche Modulation and Tumor Metastasis Suppression”. Tianze Jiang, a PhD student from School of Pharmacy of Fudan University, is the first author of this paper. Prof. Jun Chen from School of Pharmacy of Fudan University and Prof. Xiaoling Gao from Shanghai Jiao Tong University are the co-corresponding authors. This work was supported by National Natural Science Foundation of China and “Shu Guang” project funded by Shanghai Municipal Education Commission and Shanghai Education Development Foundation.

Illustration of metformin and DHA hybrid micelles for pre-metastatic niche modulation.