Emerging nanotechnological approaches to regulating tumor vasculature for cancer therapy

Abnormal angiogenesis stands for one of the most striking manifestations of malignant tumor. The pathologically and structurally abnormal tumor vasculature facilitates a hostile tumor microenvironment, providing an ideal refuge exclusively for cancer cells. The emergence of vascular regulation drugs has introduced a distinctive class of therapeutics capable of influencing nutrition supply and drug delivery efficacy without the need to penetrate a series of physical barriers to reach tumor cells. Nanomedicines have been further developed for more precise regulation of tumor vasculature with the capacity of co-delivering multiple active pharmaceutical ingredients, which overall reduces the systemic toxicity and boosts the therapeutic efficacy of free drugs. Additionally, precise structure design enables the integration of specific functional motifs, such as surface-targeting ligands, droppable shells, degradable framework, or stimuli-responsive components into nanomedicines, which can improve tissue-specific accumulation, enhance tissue penetration, and realize the controlled and stimulus-triggered release of the loaded cargo. This review describes the morphological and functional characteristics of tumor blood vessels and summarizes the pivotal molecular targets commonly used in nanomedicine design, and then highlights the recent cutting-edge advancements utilizing nanotechnologies for precise regulation of tumor vasculature. Finally, the challenges and future directions of this field are discussed.