An in situ microenvironmental nano-regulator to inhibit the proliferation and metastasis of 4T1 tumor.
【作者】 Huijuan Zhang, Xiaoge Zhang, Yanping Ren, Fang Cao, Lin Hou, Zhenzhong Zhang
【期刊名】 Theranostics
【影响因子】 2019年:8.12
【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
【年，卷(期)：页码】2019, 9(12): 3580-3594
【关键词】 mesoporous Prussian blue, low molecular weight hyaluronic acid, tumor microenvironment, SDT,tumor associated macrophages
【摘要】Tumor microenvironment, such as hypoxia and presence of immune cells, plays a critical role incancer initiation, growth as well as progression, and seriously affectsantitumor effect. Accordingly,we constructed a kind of multifunctional nanoparticles (NPs) with macrophage transformation andoxygen (O2) generation characteristics, to regulate the tumor microenvironment.Methods: In this study, we synthesized mesoporous Prussian blue (MPB) NPs with low molecularweight hyaluronic acid (LMWHA) surface modification (LMWHA-MPB), and discovered thatLMWHA-MPB could be used as an in situ macrophages converter and O2 generator.Results: In vitro results showed after uptake by M2 macrophages, LMWHA-MPB displayed thepotential in remodeling tumor-associated macrophages (TAMs) phenotype (pro-tumorM2→anti-tumor M1), and anti-metastatic effect on 4T1 cells. Furthermore, in vivo visualizednear-infrared (NIR) imaging data proved IR783 labeled LMWHA-MPB NPs could selectively
accumulate in tumor sites. Then plenty of O2 generated to alleviate tumor hypoxia via catalyticdecomposition of endogenous hydrogen peroxide (H2O2). Based on these outstandingcharacteristics, LMWHA-MPB NPs were adopted as multifunctional nanocarriers to loadsonosensitizer hematoporphyrin monomethyl ether (HMME) for O2 self-provided sonodynamictherapy (SDT). In vivo anti-tumor results showed LMWHA-MPB/HMME could effectively inhibit theproliferation and metastasis of 4T1 tumors by improving tumor microenvironment.Conclusion: The multifunctional NPs can be used as in situ microenvironmental nano-regulatorsto inhibit the proliferation and metastasis of 4T1 tumor.
【全文链接】https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587164/
