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

Abstract

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.