Theme：From active targeting to precise targeting: overcoming the on-target toxicity

Host：Dr. Zhen Li

Time：24th November 2022, 16:00-17:40

Location: Online

Active targeting-based therapies could be led astray when target molecules are expressed on non-target cells, and the on-target toxicity poses critical challenges to clinical applications. Here, a captivating affinity-filtering strategy is proposed as a feasible solution for such challenges. We have made a preliminary exploration by using the antibacterial peptides(AMPs) as the targeting moiety. Based on the selective affinity of AMPs toward distinct phospholipids, the membrane of host cells (e.g., erythrocytes) is pre-bound to AMPs as the “filter,” which could screen out non-target substances with low affinity while maintaining effective interaction with high-affinity pathogens through competitive binding, realizing precise targeting, and enhanced stability. The practicability of the affinity-filtering strategy has been demonstrated both in vitro and in vivo, through systematic studies on various peptide and peptide-modified delivery systems with multiple infection models. In addition, we also discussed a potential multi-target synergy approach, which can selectively activate the don't-eat me-signal to achieve differentiation between M1 and M2 macrophages.