Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer-TLR-7/8a) and evaluated how varying physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer-TLR-7/8a was critical for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer-TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular platform in which protein antigens are site-specifically linked to temperature-responsive polymer-TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.

An important challenge in the field of protein bioconjugation is the development of strategies that can modify a protein once at a single site. Although many bioconjugation reactions can functionalize specific amino acids in aqueous solution, [1] most proteins display multiple copies of the targeted residue on their surface. This commonly results in product mixtures that present the new functionality in multiple locations on the protein surface. As it is one of the rarest amino acids, [2] cysteine is the most commonly targeted residue when siteselective modification is required, but there remain many situations in which the modification of a unique copy of this residue is inconvenient or impossible. To address these limitations, several chemoselective techniques have been developed to target surface-accessible aromatic residues.[3]To complement these methods further, we report herein a biomimetic transamination reaction that can modify the N terminus of proteins and peptides under mild conditions. This technique introduces a uniquely reactive ketone or aldehyde group in a single location, thus allowing further modification through oxime or hydrazone formation. This simple strategy does not require the use of site-directed mutagenesis, and therefore has the potential to introduce virtually any functional group on a wide range of protein substrates.The unique reactive properties of the N terminus have resulted in several strategies targeting this location to achieve site-selective protein modification. To a limited extent, the lower pK a value of N-terminal amino groups (relative to lysine side chains) can be used to direct acylation reactions to[*] J.