Chemodynamic therapy (CDT) based intracellular chemical reactions to produce highly cytotoxic reactive oxygen species has received wide attention. However, low efficiency of single CDT in weakly acidic pH and glutathione (GSH) overexpressed tumor cells has limited its clinical application. For this study were prepared two-dimensional metal–organic framework (MOF) to improve CDT efficiency based on the combined action of bimetallic CDT, consumption of overexpressed glutathione (GSH) in cells, folic acid (FA) induced tumor targeting and triphenylphosphine (TPP) induced mitochondrial targeting. With the use of Cu­(II) as the central ion and tetrakis­(4-carboxyphenyl)­porphyrin (TCPP) as the ligand, two-dimensional Cu-MOF nanosheets were prepared, which were surface modified by manganese dioxide based on the in situ redox reaction between poly­(allylamine hydrochloride) (PAH) and KMnO4 to obtain Cu-MOF@MnO2. Then FA and TPP were coupled with the nanosheets to form the title nanoplatform. Comprehensive physiochemical research has suggested that Cu­(II) and MnO2 constituents in the nanoplatform could consume intracellular GSH and hydrogen peroxide to generate hydroxyl radicals through a Fenton-like reaction; meanwhile Cu­(II) could undergo a Russell reaction to produce cytotoxic singlet oxygen. Detailed in vitro and in vivo biological experiments have revealed a good biosafety profile and a high tumor suppression effect. Therefore, the present research has realized multiple and efficient CDT effects with the aid of the sequential targeting of FA/TPP, also providing a strategy for the development of CDT drugs based on polymetallic organic frameworks.

Small-and medium-sized cyclopeptides have been found to have extensive bioactivities and have drawn much attention from medicinal chemists. In the work described in this paper, various cyclic peptide analogs of Fenestin A were synthesized by intramolecular photoinduced electron-transfer cyclization reactions to study the influence of slight structural changes on the bioactivity of small cyclopeptides. The incorporation of thiazole and rigid isoindolinone fragments was found to improve the bioactivity of the cyclopeptide. Detailed in vitro studies of the apoptosis mechanism, mitochondrial membrane potential, cell cycle, intracellular Ca 2+ concentration, and lactate dehydrogenase activity following treatment with a cyclopeptide showed that the cyclopeptide could induce apoptosis of tumor cells and lead to cycle arrest in the G2/M phase. The research also suggested that the photoinduced reaction could be applied to construct cyclic peptides stereoselectively, and the introduction of rigid fragments could enhance the biological activity of cyclopeptide drugs.

Red carbon dot-doped Cu-MOF nanoplatform was fabricated and used in combination with immune checkpoint blockade antitumor therapy.

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