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./nMethods: 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./nResults: 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./nConclusion: This cascade H₂S-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.

中文翻译：

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ZnS @ ZIF-8核壳纳米粒子与ICG和TPZ结合使用，可实现H2S增强的协同治疗。

缺氧，间质性高血压和低pH等异常的肿瘤微环境导致当前肿瘤治疗的意外耐药性。呈现出对肿瘤微环境（TME）具有响应特性的通用药物递送系统的开发已经广泛进行，但是仍然具有挑战性。在这项研究中，沸石咪唑酯骨架-8（ZIF-8）涂覆的纳米颗粒的ZnS已经设计和ICG / TPZ分子的共同递送，表示为ZSZIT，为H制备₂ S-扩增协同therapy./n方法：该ZSZ纳米粒子使用SEM，TEM和XRD表征。在体外通过细胞计数试剂盒8（CCK-8）分析评估在常氧/低氧条件下用ZSZIT培养的癌细胞的活力。此外，还使用雄性Balb / c裸鼠作为动物模型进行了体内抗肿瘤作用。/n结果： ZSZIT在808nm NIR辐射下显示出PDT级联和缺氧激活的化学治疗作用。同时，ZSZIT在肿瘤酸性环境中降解，ZnS核产生的H ₂ S可以抑制过氧化氢酶的表达，从而有利于TPZ药物的低氧和抗肿瘤作用。二者在体外和体内研究证明为H ₂基于级联PDT /化疗S-致敏协同抗肿瘤效果。/ n的结论：这种级联的H ₂ S敏化协同纳米平台已使更有效和持久的抗癌治疗成为可能。