Degradable Nanocarriers Capable of Gene Delivery Derived from pH‐Responsive Polyester: RROP Copolymerization Between Cyclic Ketene Acetals

The ability to combine biodegradability with responsive units by radical ring-opening polymerization (RROP) is the ideal setup for a modern drug delivery system. Since the required polymers were recently unlocked by RROP copolymerization between different cyclic ketene acetals (CKAs), we herein prepared a series of polyester copolymers derived from an amine-bearing CKA 6-(iso-propyl)-2-methylene-1,3,6-dioxazocane (ⁱPr-MAC) and 2-methylene-1,3,6-trioxocane (MTC). Functional nanoparticles with tunable sizes and extremely narrow size distributions could be achieved from these copolymers. Comprehensive studies showed that the resulting nanoparticles exhibited tuneable pH-transition points from 6.3 to 7.1 as the ⁱPr-MAC content increased from 10 to 40 mol%, enabling precise pH-triggered control release at varying pH levels. Furthermore, this work demonstrates the potential of these pH-sensitive polyesters as an alternative to traditional polycations, exploring their biocompatibility and gene delivery capability, which suggests a new application prospect for CKA-derived functional polyesters.