State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, P.R. China.
Key Laboratory of Endoscopic Technique Research of Zhejiang Province, Sir Run Shaw Hospital, Zhejiang University, Hangzhou 310016, P. R. China.
Theranostics. 2020 Jun 18;10(17):7671-7682. doi: 10.7150/thno.45079. eCollection 2020.
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 HS-amplified synergistic therapy. The ZSZ nanoparticles were characterized using SEM, TEM and XRD. The viabilities of cancer cells cultured with ZSZIT under normoxia/hypoxia conditions were evaluated by cell counting kit-8 (CCK-8) assay. In addition, anti-tumor effect was also performed using male Balb/c nude mice as animal model. ZSZIT shows cascade PDT and hypoxia-activated chemotherapeutic effect under an 808nm NIR irradiation. Meanwhile, ZSZIT degrades under tumor acidic environment, and HS produced by ZnS cores could inhibit the expression of catalase, which subsequently favors the hypoxia and antitumor effect of TPZ drug. Both and studies demonstrate the HS-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy. This cascade HS-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.
异常的肿瘤微环境，如缺氧、间质高血压和低 pH 值，导致当前肿瘤治疗产生意料之外的耐药性。具有响应肿瘤微环境（TME）特性的多功能药物输送系统的开发已经广泛进行，但仍然具有挑战性。在这项研究中，设计并制备了沸石咪唑酯骨架-8（ZIF-8）包覆的 ZnS 纳米粒子用于共递送 ICG/TPZ 分子，记为 ZSZIT，用于 HS 放大协同治疗。使用 SEM、TEM 和 XRD 对 ZSZ 纳米粒子进行了表征。通过细胞计数试剂盒-8（CCK-8）测定评估了在常氧/缺氧条件下培养的癌细胞与 ZSZIT 一起的活力。此外，还使用雄性 Balb/c 裸鼠作为动物模型进行了抗肿瘤效果研究。在 808nm NIR 照射下，ZSZIT 表现出级联 PDT 和缺氧激活的化学治疗效果。同时，ZSZIT 在肿瘤酸性环境下降解，ZnS 核产生的 HS 可以抑制过氧化氢酶的表达，从而有利于 TPZ 药物的缺氧和抗肿瘤作用。和研究都证明了基于级联 PDT/化疗的 HS 敏化协同抗肿瘤效果。这种级联 HS 敏化协同纳米平台实现了更有效和持久的抗癌治疗。
