Bioactive Peptide Brush Polymers via Photoinduced Reversible‐Deactivation Radical Polymerization

Abstract

Harnessing metal‐free photoinduced reversible‐deactivation radical polymerization (photo‐RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme‐responsive and pro‐apoptotic peptide brush polymers. Thermolysin‐responsive peptide‐based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm‐like micelles upon enzyme‐triggered cleavage of coronal peptide sidechains. Moreover, pro‐apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro‐apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo‐RDRP, make it possible to access well‐defined peptide‐based polymer bioconjugate structures with tunable bioactivity.

3D Printing of Customized Drug Delivery Systems with Controlled Architecture via Reversible Addition‐Fragmentation Chain Transfer Polymerization

“…[ 61–63 ] It should be noted that polymers having a terminal RAFT moiety have been extensively studied for their toxicity and have been found to be both easy to remove after manufacture and nontoxic in vitro. [ 64 ]…”

“…[61][62][63] It should be noted that polymers having a terminal RAFT moiety have been extensively studied for their toxicity and have been found to be both easy to remove after manufacture and nontoxic in vitro. [64] Changes to the crosslinker average molecular weight can affect printability, so 3D printing parameters were varied to optimize the printing. Initially, parameters as per entry 17 in Table 1 were used: Cure time of 25 s per 100 μm layer and PEGDA250 was replaced with PEGDA700; all other parameters were kept constant.…”

Caspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers

“…To date, BBP linkers that respond to light, pH, diols, reactive oxygen species, and esterases have been reported; − however, despite their established use in linear, block, and bottlebrush polymer synthesis via ROMP, , peptides have not yet been employed as linkers in the context of BBPs. Thus, while polymers with cleavable peptide side chains can display enhanced stability yet remain accessible to enzymatic cleavage, − the impact of the BBP molecular architecture on protease access to peptide linkers is unknown. Prior studies on the use of nitroxide labels to probe the local environment and accessibility of reactive species to molecular bottlebrushes and BBPs have shown substantially different rates of reaction (e.g., nitroxide reduction) as a function of the nitroxide location (e.g., the periphery, backbone ends, and backbone middle). , Thus, we hypothesized that the precise placement of cleavable peptides within BBPs could provide control of the rate of protease cleavage based on steric hindrance, thus offering a design strategy for triggered release in such systems.…”

Stable and Recyclable Photocatalysts of CsPbBr3@MSNs Nanocomposites for Photoinduced Electron Transfer RAFT Polymerization

“…Great efforts have been devoted to advancing photoinduced reversible-deactivation radical polymerizations (RDRP) for the preparation of macromolecules with multiple architectures, high spatial and temporal resolution, and precise chemical composition under mild reaction conditions. − Recent efforts in utilizing lead halide perovskite and perovskite-based nanocomposites for photodriven radical polymerization have demonstrated catalytic properties comparable or superior to the traditional organic photocatalysts, metal complexes, and emerging semiconductors. − For example, the reductive potentials of excited CsPbBr 3 NCs and typical activated reversible addition–fragmentation chain transfer (RAFT) agents were −1.3 V and −0.3 to −0.8 V, respectively (versus a saturated calomel electrode, SCE). ,, The reductive potential of CsPbBr 3 was sufficiently negative to activate typical RAFT agents, allowing the transfer of photogenerated electrons from NCs to the RAFT agents to induce RAFT polymerization. , Therefore, CsPbBr 3 can be a potent photocatalyst for photoinduced electron transfer RAFT (PET-RAFT) polymerization. However, the instability of CsPbBr 3 toward ultraviolet (UV) light, heat, and moisture lead to NC degradation, PL loss, and poor optoelectronic efficiencies, which prevent its practical applications. − …”