Ultra-stable MOF@MOF nanoplatform for photodynamic therapy sensitized by relieved hypoxia due to mitochondrial respiration inhibition

by Selleckchem | Jan 16 2024

Metal-organic frameworks (MOFs) with periodically arranged porphyrinic linkers avoiding the self-quenching issue of porphyrins in photodynamic therapy (PDT) have been widely applied. However, the porphyrinic MOFs still face challenges of poor stability under physiological conditions and limited photodynamic efficiency by the hypoxia condition of tumors. Herein, we fabricate the MOF@MOF structure with a protective MOF shell to improve the stability and relieve the hypoxia condition of tumors for sensitized PDT. Under protection of the MOF shell, the MOF@MOF structure can keep intact for 96 h under physiological conditions. Consequently, the tumoral accumulation efficiency is two folds of the MOF core. Furthermore, the MOF shell decomposes under acidic environment, and the loaded inhibitor of mitochondria pyruvate carrier (7-amino carboxycoumarins-2, 7ACC2) will be released. 7ACC2 inhibits the mitochondrial pyruvate influx and simultaneously blocks glucose and lactate from fueling the mitochondrial respiration, thereupon relieving the hypoxia condition of tumors. Under a 5-min laser irradiation, the 7ACC2 carrying MOF@MOF nanoplatforms induced doubled cellular apoptosis and reduced 70% of the tumor growth compared with the cargo-free MOF@MOF. In summary, the design of this stable and hypoxia self-relievable MOF@MOF nanoplatform will enlighten the future development of MOF-based nanomedicines and PDT. STATEMENT OF SIGNIFICANCE: Though widely used for photodynamic therapy (PDT) in previous studies, porphyrinic metal-organic frameworks (MOFs) still face challenges in poor stability under physiological conditions and limited photodynamic efficiency due to the hypoxia condition of tumors. In order to solve these problems, (1) we develop the MOF@MOF strategy to improve the physiological stability; (2) an inhibitor of mitochondria pyruvate carrier, 7-amino carboxycoumarins-2 (7ACC2), is loaded to inhibit the mitochondrial pyruvate influx and simultaneously block glucose and lactate from fueling the mitochondrial respiration, thereupon relieving the hypoxia condition of tumors. In comparison with previous studies, our strategy simultaneously improves stability and overcomes the limited PDT efficiency in the hypoxia tumor tissue, which will enlighten the future development of MOF-based nanomedicines and PDT.

Comments:

Your work on developing a MOF@MOF structure for improved stability and enhanced photodynamic therapy (PDT) efficiency sounds fascinating! By addressing the challenges of poor stability under physiological conditions and limited efficacy in hypoxic tumor environments, you've taken a significant step forward in MOF-based nanomedicines.

The protective MOF shell you've introduced seems to effectively enhance stability, allowing the structure to remain intact for an extended period under physiological conditions. Moreover, the inclusion of an inhibitor like 7ACC2 holds immense promise. By inhibiting mitochondrial pyruvate influx and disrupting glucose and lactate utilization, you're effectively mitigating the hypoxic conditions in tumors.

The results you've obtained are impressive. Doubling cellular apoptosis and significantly reducing tumor growth compared to cargo-free MOF@MOF underlines the efficacy of your design. This not only improves the therapeutic potential but also demonstrates the significance of your approach in overcoming challenges previously encountered with porphyrinic MOFs in PDT.

Your work seems poised to advance the field by offering a solution that simultaneously enhances stability and addresses the limitations of PDT in hypoxic tumor tissues. This development indeed holds promise for future advancements in MOF-based nanomedicines and their application in PDT.