ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable HS-amplified synergistic therapy.

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.