Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small‐molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum‐protein‐binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph‐node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.

Via a smart combination of temperature-responsive and acid labile acetal monomers, copolymers are obtained with à la carte lower critical solution temperature behavior. RAFT copolymerization of these monomers using, respectively, a PEG-functionalized or amine-reactive NHS-functionalized chain transfer agent allows designing of micelles and polymer-protein conjugates with transient solubility properties within a physiologically relevant window.

a Efficient polymer-protein conjugation is a crucial step in the design of many therapeutic protein formulations including nanoscopic vaccine formulations, antibody-drug conjugates and to enhance the in vivo behaviour of proteins. Here we aimed at preparing well-defined polymers for conjugation to proteins by reversible addition-fragmentation chain transfer (RAFT) polymerization of both acrylates and methacrylamides with protein-reactive chain transfer agents (CTAs). These RAFT agents contain either a N-hydroxysuccinimide (NHS) or pentafluorophenyl (PFP) ester moiety that can be conjugated to lysine residues, and alternatively a maleimide (MAL) or pyridyl disulfide (PDS) moiety that can be conjugated to cysteine residues. Efficiency of the bioconjugation of these polymers to bovine and avian serum albumin was investigated as a function of stoichiometry, polymer molecular weight and the presence of reducing agents. A large molar excess of polymer was required to obtain an acceptable degree of protein conjugation.However, protein modification with N-succinimidyl-S-acetylthiopropionate (SATP) to introduce sulfhydryl groups onto primary amines, significantly increased conjugation efficiency with MAL-and PDS-containing polymers.

Living cells are anchored with magnetic microcapsules that allow in vitro manipulation via a magnetic field.