Emerging landscapes of nanosystems based on pre-metastatic microenvironment for cancer theranostics

The emergence of disseminated metastasis is the leading cause of mortality in patients with malignant tumor. The pre-metastatic microenvironment, including the primary tumor-derived components, pre-metastatic niche (PMN), circulating tumor cells (CTCs), micro-metastases, and tumor immune microenvironment (TIM), are the crucial factors to initiate metastasis and form macro-metastases. It may be a more promising strategy for directly targeting pre-metastatic microenvironment-interrelated factors and cells before they have the chance to form secondary tumors to prevent metastasis. During recent years, a variety of nanosystems, with specific microstructures and functional properties, have been devised to selectively target pre-metastatic cells components and interrelated molecular, and exhibited strong potential on anti-metastatic therapy by absorbing and neutralizing primary tumor-derived components, preventing establishment of the PMN, eliminating the CTCs, eradicating the micro-metastases and modulating the TIM. In this review, we comprehensively review the emerging nanosystems based on the pre-metastatic microenvironments. Hopefully, this review can cast new lights for early preventing and attenuating metastatic progression. Graphical abstract This review focuses on the emerging nanosystems based on pre-metastatic microenvironment and discusses the progress in the application of nanotechnology from the perspective of targeting and regulating abnormally expressed biochemical molecules and interrelated accessory cells in the early stage of cancer metastasis. .