Injectable dual-affinity self-assembling peptide hydrogels for local controlled delivery of therapeutic antibodies

Abstract

Therapeutic monoclonal antibodies have revolutionized the treatment of cancers, infectious diseases and immune disorders; however, their efficacy is compromised by limitations associated with systemic administration, including systemic toxicity, poor patient compliance and inadequate drug concentration at pathological sites. Hydrogels are promising carriers for localized antibody delivery, but conventional formulations fail to simultaneously address the dual challenges of uncontrolled antibody release and insufficient hydrogel retention at the target site. Herein, leveraging a peptide co-assembly strategy, we engineered an injectable dual-affinity self-assembling peptide hydrogel for localized antibody delivery. This hydrogel integrates three components: peptide FEK as the hydrogel matrix, MEP-FEK incorporating 4-mercaptoethylpyridine (MEP) for non-covalent antibody binding, and C₁BP-FEK functionalized with the collagen-binding peptide TKKTLRT for tumor extracellular matrix anchoring. The dual-affinity hydrogel enabled controlled antibody release, exhibiting only 40% cumulative release by Day 90 and an 8.8-fold reduction in initial diffusion rate. In proof-of-concept studies using SKOV3 tumor-bearing mice, the hydrogel carrying trastuzumab as a model therapeutic antibody enhanced local antibody retention, reduced. systemic exposure, exhibited negligible toxicity, and achieved a tumor inhibition rate of 68% This dual-affinity strategy overcomes limitations of conventional affinity-based hydrogels, providing a biocompatible and versatile platform for localized antibody therapy in oncology and other biomedical applications.