Anti-angiogenic nano-delivery system promotes tumor vascular normalizing and micro-environment reprogramming in solid tumor
Journal of Controlled Release(2022)
摘要
Aberrant tumor vasculature leads to the malignant tumor microenvironment (TME) for tumor progression. Research has found temporary tumor vascular normalization after treated with low-dose anti-angiogenic agents, however, has paid little attention to prolonging the normalization window and its further influence on tumor tissue. Based on the dose- and time-dependent effect of anti-angiogenic agents, we developed V@LDL NPs, a nano-delivery system sustainedly releasing Vandetanib, an anti-VEGFR2 inhibitor, to control the dose of drug to the normalizing level, and prove its stable tumor vascular normalizing effect in 4 T1 breast cancer model. Furthermore, long-term normalized vasculature could improve tumor perfusion, then provide a circulation to reverse abnormalities in TME, such as hypoxia and heterogeneity, and also inhibit tumor progression. Our findings demonstrate that stable tumor vascular normalization could be a considerable strategy for long-term change to remodel TME and probably result in a therapeutic benefit to anti-cancer treatment, which could be achieved by anti-angiogenic nano-delivery system.
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关键词
Angiogenesis,Tumor vascular normalization,Nano-delivery system,Tumor microenvironment reprogramming
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