posted on 2021-06-24, 14:10authored byShuang Chen, Xiaohong Yang, Yan Zhang, Yun Liu, Hui Lu, Yanfei Qiu, Liting Cheng, Chong Li, Chenhui Wang
Cancer metastasis is the major cause
of cancer-related death; therefore,
achieving suppression of tumor metastasis is a long-sought goal in
cancer therapy. As the premetastatic niche acts as a prerequisite
for tumor metastasis, it serves as an effective target for metastasis
suppression. This study tests the feasibility of inhalable porous
microspheres loaded with two premetastatic niche modulation agents,
metformin and docosahexaenoic acid, as orthotopic delivery carriers
for the reversion of lung premetastatic microenvironments and targeted
suppression of tumor lung metastasis. The microspheres were prepared via an improved emulsion-solvent evaporation method and
exhibit an excellent lung deposition, leading to significant inhibition
of circulating tumor cells (CTCs)–endothelial cells adhesion,
reduction of vascular permeability, and suppression of adhesion protein
expression in lung premetastatic microenvironments. As a result, inhalable
microspheres can prevent tumor lung metastasis formation excellently in vivo. Overall, this study proved that the encapsulation
of metformin and docosahexaenoic acid in inhalable microspheres could
be a promising strategy for tumor lung metastasis inhibition via orthotopically modulating premetastatic niche in the
lungs.