Synergistic Effects of Polycationic and Polyfluorinated Functionalities for Efficient Intracellular Protein Delivery

Intracellular protein therapy is a promising strategy in biologics, including vaccine development, gene editing, and cancer therapeutics. However, protein-based drug delivery remains a significant challenge, particularly in penetrating cell barriers to reach intracellular targets. Inspired by transport adjuvants, we designed a series of polymeric vectors to achieve efficient functional protein trafficking with low cytotoxicity. With an adequate combination of guanidinium and fluorocarbon functionalities, a synergistic improvement of intracellular delivery is achieved in terms of both high intracellular transport and low cellular toxicity. The observed synergistic outcomes highlight new opportunities for delivery vehicle optimizations of intracellular biologics.