Poly(amidoamine) (PAMAM) encapsulated platinum nanoparticles were synthesized and used as catalase mimics. Acetylated generation 9 (Ac-G9) PAMAM dendrimer with a molecular size around 10 nm was used as a template to synthesize platinum nanoparticles. The feeding molar ratio of Pt(4+) and Ac-G9 is 2048, and the synthesized platinum nanoparticle (Ac-G9/Pt NP) has an average size of 3.3 nm. Ac-G9/Pt NP has a similar molecular size and globular shape with catalase (~11 nm). The catalytic activity of Ac-G9/Pt NP on the decomposition of H2O2 is approaching that of catalase at 37 °C. Ac-G9/Pt NP shows differential response to the changes of pH and temperature compared with catalase, which can be explained by different catalytic mechanisms of Ac-G9/Pt NP and catalase. Ac-G9/Pt NP also shows horseradish peroxidase activity and is able to scavenge free radicals such as di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH). Furthermore, Ac-G9/Pt NP shows excellent biocompatibility on different cell lines and can down-regulate H2O2-induced intracellular reactive oxygen species (ROS) in these cells. These results suggest that dendrimers are promising mimics of proteins with different sizes and Ac-G9/Pt NP can be used as an alternative candidate of catalase to decrease oxidation stress in cells.
Tumor necrosis factor-alpha (TNF-α) neutralization has become increasingly important in the treatment of inflammatory bowel diseases (IBD). A series of monoclonal antibodies were approved in the clinic for anti-TNF-α therapy. However, a comprehensive assessment of TNF-α levels throughout the colon, which facilitates the diagnosis of IBD and predicts anti-TNF-α efficacy, remains challenging. Here, we radiolabeled infliximab with long-lived radionuclides 89 Zr for immuno-positron emission tomography (PET) imaging of TNF-α in vivo. The increased TNF-α level was detected in the inflammatory colon of the dextran sodium sulfate-induced colitis mice. The immuno-PET imaging of 89 Zr-desferrioxamine-infliximab reveals a high uptake (7.1 ± 0.3%ID/g) in the inflammatory colon, which is significantly higher than in the healthy control and blocked groups. The colon-tomuscle ratio reached more than 10 and was maintained at a high level for 10 h after injection. The ex vivo biodistribution study also verified the superior uptake in the inflammatory colon. This study provides an in vivo immune-PET approach to molecular imaging of the pro-inflammatory cytokine TNF-α. It is promising in diagnosing and predicting efficacy in both IBD and other autoimmune diseases.
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