PET‐RAFT as a facile strategy for preparing functional lipid–polymer conjugates

From readily available starting materials, we report a facile synthesis of lipid–polymer conjugates (LPCs). Easy access to multigram quantities of a dialkyl lipid chain transfer agent allows a range of LPCs to be prepared bearing well-defined hydrophilic polymer head-groups, controlled molecular weights and low dispersity by photoelectron transfer RAFT polymerization (PET-RAFT). As dictated by the lipid packing parameters, the resulting LPCs were suitable for solution-phase self-assembly, both independently and in combination with naturally occurring phospholipids, affording micelles, smaller vesicle-like structures, or stabilized large unilamellar vesicles. Notably, co-assembly of LPCs and phospholipids bearing mutually orthogonal fluorophores showed negligible phase separation/aggregation. To demonstrate the versatility of these LPCs, the RAFT chain-end was removed, affording thiol-terminated LPCs that could be used for the manipulation and stabilization of gold nanoparticle assemblies. Facile access to structurally diverse LPC building blocks enables a variety of biotechnology and biomedical applications, including drug-delivery, cell engineering, and 3D-printed biomaterials.