Mimotope peptide modified pompon mum-like magnetic microparticles for precise recognition,capture and biotransformation analysis of rituximab in biological fluids

Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.

Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint signaling.Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress.Furthermore,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.