Biomechanical forces and force-triggered drug delivery in tumor neovascularization - 04/02/24
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
The biomechanical forces in the tumor microenvironment and biomechanical force-triggered drug delivery system. (a) Topology, also termed matrix structure, is formed by the tension of tumor cells, excessive proliferation of tumor cells, and matrix remodeling. Tumor upregulate angiogenesis and produce an abnormal vasculature network to meet nutrient demand. (b) ECM stiffness modulates cell-cell junctions and localization of VE cadherin, disrupting barrier function and increasing permeability. (c) Solid stress, generating by ECM deposition and proliferating stromal and cancer cells, causes tumor vascular compression. (d) Elevated interstitial fluid pressure (IFP) often exceeds the microvascular pressure (MVP), causing limited perfusion and anomalous flow patterns. Tumor vascular drug release in biomechanical force-triggered drug delivery system: (e) polymer dissociation; (f) nanoparticle deformation.
The biomechanical forces in the tumor microenvironment and biomechanical force-triggered drug delivery system. (a) Topology, also termed matrix structure, is formed by the tension of tumor cells, excessive proliferation of tumor cells, and matrix remodeling. Tumor upregulate angiogenesis and produce an abnormal vasculature network to meet nutrient demand. (b) ECM stiffness modulates cell-cell junctions and localization of VE cadherin, disrupting barrier function and increasing permeability. (c) Solid stress, generating by ECM deposition and proliferating stromal and cancer cells, causes tumor vascular compression. (d) Elevated interstitial fluid pressure (IFP) often exceeds the microvascular pressure (MVP), causing limited perfusion and anomalous flow patterns. Tumor vascular drug release in biomechanical force-triggered drug delivery system: (e) polymer dissociation; (f) nanoparticle deformation.ga1Le texte complet de cet article est disponible en PDF.
Highlights |
• | Introducing the regulatory mechanisms of the biomechanical forces on angiogenesis. |
• | The feasibility of biomechanical force-triggered drug delivery systems in angiogenesis. |
• | The biomechanical force combined with anti-angiogenic therapy is promising approach. |
Abbreviations : VEGF, FGF, Ang, EGF, PDGF, HIF-1, TME, ECM, ECs, IFP, MVP, CTCs, FAK, ERK1/2, CAFs, LOX, EMT, TECs, MMPs, VE-Cadherin, HCC, YAP, PECAM-1, TRPV4, GPCRs, ROCK
Keywords : Biomechanical forces, Tumor neovascularization, Biomechanical force-triggered, Drug delivery, Biomechanical microenvironment
Plan
Vol 171
Article 116117- février 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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