ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H 2 S-amplified synergistic therapy
ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H 2 S-amplified synergistic therapy
复制标题
ZnS@ZIF-8核壳纳米颗粒与ICG和TPZ结合，实现H2S放大协同治疗
DOI：
10.7150/thno.45079
复制
发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Han, Gaorong
中科院分区：
文献类型：
--
作者：
Fang, Chao;Cen, Dong;Han, Gaorong
异常的肿瘤微环境，如缺氧、间质高压和低pH，导致当前肿瘤治疗的意想不到的抵抗。对肿瘤微环境（TME）具有响应特性的多功能药物递送系统的开发已被广泛开展，但仍然具有挑战性。在这项研究中，沸石咪唑骨架-8（ZIF-8）包覆的ZnS纳米粒子已被设计和制备用于共递送ICG/TPZ分子，表示为ZIF ZIT，用于H2S放大的协同治疗。方法：采用扫描电镜、透射电镜、X射线衍射等方法对纳米粒进行表征。用CCK-8法检测常氧/低氧条件下与ZIT共同培养的癌细胞的体外存活率。此外，还使用雄性Balb/c裸鼠作为动物模型进行体内抗肿瘤作用。结果：在808 nm近红外光照射下，丹参酮Ⅱ A具有光动力学级联效应和缺氧激活化疗效应。同时，TPZ在肿瘤酸性环境中降解，ZnS核产生的H2S抑制过氧化氢酶的表达，有利于TPZ药物的耐缺氧和抗肿瘤作用。体外和体内研究均证实了基于级联PDT/化疗的H2S敏化协同抗肿瘤作用。结论：这种级联H2S敏化协同纳米平台能够实现更有效和持久的抗癌治疗。
Abnormal tumor microenvironment, such as hypoxia, interstitial hypertension and low pH, leads to unexpected resistance for current tumor treatment. The development of versatile drug delivery systems which present responsive characteristics to tumor microenvironment (TME) has been extensively carried out, but remains challenging. In this study, zeolitic imidazolate framework-8 (ZIF-8) coated ZnS nanoparticles have been designed and prepared for co-delivery of ICG/TPZ molecules, denoted as ZSZIT, for H2S-amplified synergistic therapy. Methods: The ZSZ nanoparticles were characterized using SEM, TEM and XRD. The in vitro viabilities of cancer cells cultured with ZSZIT under normoxia/hypoxia conditions were evaluated by cell counting kit-8 (CCK-8) assay. In addition, in vivo anti-tumor effect was also performed using male Balb/c nude mice as animal model. Results: ZSZIT shows cascade PDT and hypoxia-activated chemotherapeutic effect under an 808nm NIR irradiation. Meanwhile, ZSZIT degrades under tumor acidic environment, and H2S produced by ZnS cores could inhibit the expression of catalase, which subsequently favors the hypoxia and antitumor effect of TPZ drug. Both in vitro and in vivo studies demonstrate the H2S-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy. Conclusion: This cascade H2S-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.