Immobilization of horseradish peroxidase on metal-organic framework to imporve enzyme activity for enhanced chemodynamic therapy.

Bio-enzymes have the advantages of strong substrate specificity, high catalytic efficiency, and minimal toxic side effects, making them promising drugs in cancer therapy. However, the poor stability and cellular penetrability of uncoated protein in the physiological environment severely restricts the direct application of Bio-enzyme. To address it, we report a metal-organic framework (MOF), Hf-DBA (H2DBA, biphenyl carboxylic acid ligands). The morphology of the Hf-DBA was revealed by TEM and the diameter was in the range of 200 to 350 nm. Hf-DBA acted a carrier for intracellular delivery and protection of horseradish peroxidase (HRP). The prepared HRP@Hf-DBA can catalyze the excess H2O2 in the tumor cells to generation of •OH for chemodynamic therapy (CDT). Compared with free HRP, the catalytic activity of HRP@Hf-DBA is significantly improved, and the optimal catalytic conditions are explored. The catalytic stability of HRP@Hf-DBA remained above 70% after 12 cycles of catalysis. After treatment with HRP@Hf-DBA, the apoptosis rates of A549 and Hela cells was 71.64%, and 76.86%. The results in vitro show that HRP@Hf-DBA can effectively inhibit the growth of tumor cells through enhanced CDT.

Porphyrin-Based Metal-Organic Framework Probe: Highly Selective and Sensitive Fluorescent Turn-On Sensor for M3+ (Al3+, Cr3+, and Fe3+) Ions.

The development of porphyrin-based metal-organic frameworks (MOFs) has attracted significant interest in the scientific community in recent years because of their versatile applications particularly in optical and electronic fields. In this study, a highly selective and sensitive fluorescent turn-on sensor using a porphyrinic MOF, Tb-TCPP, is presented, which displays a 10-fold fluorescence enhancement in the presence of Al3+, Cr3+, and Fe3+ ions. The detection limit is in the nM region. For the Al3+ ion, it could be visually detected at concentrations as low as 5 mM within 15 min. Tb-TCPP could also be used as an indicator for acidic or alkaline solutions at pH values of >9 and <3. The studies on the detection mechanism illustrate that cation exchange proceed between Tb-TCPP and these M3+ ions, and consequently, energy transfer from TCPP to Tb3+ is suppressed and π*-π energy transfer of the porphyrin ligand is significantly enhanced.

Metal-organic framework combined with CaO2 nanoparticles for enhanced and targeted photodynamic therapy.

Photodynamic therapy (PDT) has been rapidly developed as an effective therapeutic approach in clinical settings. However, hypoxia seriously limits the effectiveness of PDT. Here, we report a porphyrin-based metal-organic framework combined with hyaluronate-modified CaO2 nanoparticles (PCN-224-CaO2-HA) to target and enhance PDT efficacy. CaO2 reacts with H2O or weak acid to produce O2, overcoming the hypoxia problem. Hyaluronate protects CaO2 and specifically targets the CD44 receptor, which is highly expressed on tumor cell membranes, performing targeted therapy. After PDT treatment in vitro, the survival rates of 4T1 and MCF-7 tumor cells were 14.58% and 22.45%, respectively. The fluorescence imaging showed that PCN-224-CaO2-HA effectively aggregated in the tumor after 12 h of its intravenous injection into tumor-bearing mice. PCN-224-CaO2-HA exhibited efficacious tumor growth inhibition via enhanced PDT. Overall, this nanosystem providing in situ oxygen production was successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo.