AUTHOR=Liang Yujia , Cai Zhengmin , Tang Yamei , Su Chenglin , Xie Liye , Li Yan , Liang Xinqiang TITLE=H2O2/O2 self-supply and Ca2+ overloading MOF-based nanoplatform for cascade-amplified chemodynamic and photodynamic therapy JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=11 YEAR=2023 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1196839 DOI=10.3389/fbioe.2023.1196839 ISSN=2296-4185 ABSTRACT=

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 CaO₂ nanoparticles, followed by surface decoration by hyaluronic acid (HA), obtaining HA/CaO₂-Ce6@Cu-ZIF nano platform.

Results and Discussion: Once HA/CaO₂-Ce6@Cu-ZIF targets tumor sites, the degradation of Ce6 and CaO₂ release from the HA/CaO₂-Ce6@Cu-ZIF in response to the acid environment, while the Cu²⁺ active sites on Cu-ZIF are exposed. The released CaO₂ decompose to generate hydrogen peroxide (H₂O₂) and oxygen (O₂), which alleviate the insufficiency of intracellular H₂O₂ and hypoxia in tumor microenvironment (TME), effectively enhancing the production of hydroxyl radical (•OH) and singlet oxygen (¹O₂) in Cu²⁺-mediated chemodynamic therapy (CDT) and Ce6-induced photodynamic therapy (PDT), respectively. Importantly, Ca²⁺ originating from CaO₂ could further enhance oxidative stress and result in mitochondrial dysfunction induced by Ca²⁺ overloading.

Conclusion: Thus, the H₂O₂/O₂ self-supplying and Ca²⁺ overloading ZIF-based nanoplatform for cascade-amplified CDT/PDT synergistic strategy is promising for highly efficient anticancer therapy.