H2O2/O2 self-supply and Ca2+ overloading MOF-based nanoplatform for cascade-amplified chemodynamic and photodynamic therapy

Introduction: Reactive oxygen species (ROS)-mediated therapies have typically been considered as noninvasive tumor treatments owing to their high selectivity and efficiency. However, the harsh tumor microenvironment severely impairs their efficiency. Methods: Herein, the biodegradable Cu-doped zeolitic imidazolate framework-8 (ZIF-8) was synthesized for loading photosensitizer Chlorin e6 (Ce6) and CaO 2 nanoparticles, followed by surface decoration by hyaluronic acid (HA), obtaining HA/CaO 2 -Ce6@Cu-ZIF nano platform. Results and Discussion: Once HA/CaO 2 -Ce6@Cu-ZIF targets tumor sites, the degradation of Ce6 and CaO 2 release from the HA/CaO 2 -Ce6@Cu-ZIF in response to the acid environment, while the Cu 2+ active sites on Cu-ZIF are exposed. The released CaO 2 decompose to generate hydrogen peroxide (H 2 O 2 ) and oxygen (O 2 ), which alleviate the insufficiency of intracellular H 2 O 2 and hypoxia in tumor microenvironment (TME), effectively enhancing the production of hydroxyl radical (?OH) and singlet oxygen ( 1 O 2 ) in Cu 2+ -mediated chemodynamic therapy (CDT) and Ce6-induced photodynamic therapy (PDT), respectively. Importantly, Ca 2+ originating from CaO 2 could further enhance oxidative stress and result in mitochondrial dysfunction induced by Ca 2+ overloading. Conclusion: Thus, the H 2 O 2 /O 2 self-supplying and Ca 2+ overloading ZIF-based nanoplatform for cascade-amplified CDT/PDT synergistic strategy is promising for highly efficient anticancer therapy.

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