Biomechanical forces and force-triggered drug delivery in tumor neovascularization

Tumor angiogenesis is one of the typical hallmarks of tumor occurrence and development, and tumor neovascularization also exhibits distinct characteristics from normal blood vessels. As the number of cells and matrix inside the tumor increases, the biomechanical force is enhanced, specifically manifested as solid stress, fluid stress, stiffness, and topology. This mechanical microenvironment also provides shelter for tumors and intensifies angiogenesis, providing oxygen and nutritional support for tumor progression. During tumor development, the biomechanical microenvironment also emerges, which in turn feeds back to regulate the tumor progression, including tumor angiogenesis, and biochemical and biomechanical signals can regulate tumor angiogenesis. Blood vessels possess inherent sensitivity to mechanical stimuli, but compared to the extensive research on biochemical signal regulation, the study of the regulation of tumor neovascularization by biomechanical signals remains relatively scarce. Biomechanical forces can affect the phenotypic characteristics and mechanical signaling pathways of tumor blood vessels, directly regulating angiogenesis. Meanwhile, they can indirectly regulate tumor angiogenesis by causing an imbalance in angiogenesis signals and affecting stromal cell function. Understanding the regulatory mechanism of biomechanical forces in tumor angiogenesis is beneficial for better identifying and even taming the mechanical forces involved in angiogenesis, providing new therapeutic targets for tumor vascular normalization. Therefore, we summarized the composition of biomechanical forces and their direct or indirect regulation of tumor neovascularization. In addition, this review discussed the use of biomechanical forces in combination with anti-angiogenic therapies for the treatment of tumors, and biomechanical forces triggered delivery systems.