期刊
JOURNAL OF CONTROLLED RELEASE
卷 349, 期 -, 页码 550-564出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.07.015
关键词
Angiogenesis; Tumor vascular normalization; Nano -delivery system; Tumor microenvironment reprogramming
资金
- National Natural Science Foundation of China [81973267]
Abnormal tumor vasculature leads to malignant tumor microenvironment and affects tumor progression. We developed a nano-delivery system that sustains the release of anti-angiogenic agents to stabilize tumor vascular normalization, improving tumor perfusion and reversing abnormalities in the tumor microenvironment, ultimately inhibiting tumor progression.
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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