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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 H 2 S-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 H 2 S 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 H 2 S-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy. Conclusion: This cascade H 2 S-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.

ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H2S-amplified synergistic therapy

ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H₂S-amplified synergistic therapy