Emerging nanomedicines strategies focused on tumor microenvironment against cancer recurrence and metastasis

Every stage of cancer metastasis, immune surveillance evasion, and therapeutic resistance is influenced by tumor microenvironment (TME). In light of this, nanomedicines design based on remodeling TME has developed as a promising strategy to promote tumor therapy. In this review, we first introduce the formation, distribution, and properties of TME, as well as the influence of each component in TME on cancer development, metastasis, and recurrence. Subsequently, the recent advancements in nanomedicines for inhibiting tumor angiogenesis and promoting vascular normalization are described. Furthermore, new strategies for dealing with tumor hypoxia are proposed, with a particular emphasis on the innovative design of a series of nanomaterials to generate oxygen (O2), supply O2, or target tumor hypoxia. And the emerging nanotechnologies that have been established to regulate the tumor extracellular matrix (ECM), including disruption and intervention in tumor ECM production also been illustrated. New nanotherapeutics based on tumor-associated macrophages, cancer-associated fibroblast, and myeloid-derived suppressor cells are thoroughly discussed, including destruction and targeting of relevant cellular components. Also, we exemplify recent advances in nanomedicines design for immunotherapy to prevent postoperative tumor recurrence. Finally, we highlight the current challenges and possible solutions in clinical translation of TME remodeling nanomedicines against cancer recurrence and metastasis.