Functionalized Hyperbranched Polymers Derived from Kinetically Controlled Polymerization for Gene Therapy

The efficiency of drug delivery systems is of great significance in modern medicine, as it can significantly improve therapeutic outcomes and reduce side effects. Polypeptides, due to their excellent biocompatibility and diverse functional properties, have become ideal candidates for drug carriers. However, traditional polypeptide polymers still face challenges in terms of stability and delivery efficiency. To address these issues, we have developed polypeptide-functionalized cyclized/knot polymers aimed at enhancing drug delivery efficiency.<br/>In this study, through the kinetically controlled strategy, we designed and synthesized a series of polypeptide-functionalized cyclized/knot polymers with introducing monomers with different functional groups. These polymers possess condensed conformations, multiple intramolecularly cyclized structures and well-defined three-dimensional structures. By optimizing the degree of cyclization and the design of the polypeptide chains, we can precisely control the physicochemical properties of the polymers. Experimental results demonstrate that these cyclized/knot polymers exhibit excellent stability and biocompatibility under physiological conditions, as well as low toxicity.<br/>To improve drug delivery efficiency, we focused on the membrane-penetrating ability and endosomal escape characteristics of these polymers. In vitro experimental results show that polypeptide-functionalized cyclized/knot polymers have exceptional membrane-penetrating capabilities, efficiently crossing cell membranes and entering the interior of cells. Additionally, these polymers exhibit excellent endosomal escape ability in endosomal environments, effectively releasing the loaded drugs and thereby enhancing the therapeutic effects.<br/>In summary, polypeptide-functionalized cyclized/knot polymers, as a new type of drug delivery carrier, show great potential in improving drug delivery efficiency. This study not only provides new strategies and methods for the development of efficient drug delivery systems but also lays a solid foundation for future clinical applications.