Hybrid Poly(β‐amino ester) Triblock Copolymers Utilizing a RAFT Polymerization Grafting‐From Methodology

Abstract

The biocompatibility, biodegradability and responsiveness of poly(ß‐amino esters) (PBAEs) has led to their widespread use as biomaterials for drug and gene delivery. Nonetheless the step growth polymerisation mechanism which yields PBAEs limits the scope for their structural optimisation towards specific applications because of limited monomer choice and end‐group modifications. Moreover, to date the post‐synthetic functionalisation of PBAEs has relied on grafting‐to approaches, challenged by the need for efficient polymer‐polymer coupling and potentially difficult post conjugation purification. Here a novel grafting‐from approach to grow reversible addition‐fragmentation chain transfer (RAFT) polymers from a PBAE scaffold is described. This was achieved through PBAE conversion into a macromolecular chain transfer agent through a multi‐step capping procedure, followed by RAFT polymerisation with a range of monomers to produce PBAE‐RAFT hybrid triblock copolymers. Following successful synthesis, the potential biological applications of these ABA triblock copolymers were illustrated through assembly into polymeric micelles and encapsulation of a model hydrophobic drug, followed by successful nanoparticle (NP) uptake in breast cancer cells. The findings demonstrate this novel synthetic methodology can expand the scope of PBAEs as biomaterials.This article is protected by copyright. All rights reserved

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…LumiTracker Lyso Green tracker was utilized to label lysosomes to determine the cellular distribution. 43 In Figure 5 c, a significant degree of colocalization was observed between the red fluorescence of the nanosheets and the green lysosome tracker; the Pearson correlation coefficient with lysosomes in HeLa cells was high (0.71). Given the acidic environment of lysosomes, this intracellular distribution enhances the efficacy of low pH-activated PDT.…”

“…The intracellular localization of PRGD/NLG919 nanosheets was investigated through CLSM following a 2 h incubation with HeLa cells. LumiTracker Lyso Green tracker was utilized to label lysosomes to determine the cellular distribution . In Figure c, a significant degree of colocalization was observed between the red fluorescence of the nanosheets and the green lysosome tracker; the Pearson correlation coefficient with lysosomes in HeLa cells was high (0.71).…”

Triblock copolymer micelles enhance solubility, permeability and activity of a quorum sensing inhibitor against Pseudomonas aeruginosa biofilms

“…PBAE functionalisation with NHS-PABTC was conducted as previously reported in literature. 25 Briefly HDD-PIP (1 g, 1 eq.) and NHS-PABTC (6 eq.)…”

“…Grafting-from RAFT polymerisation was conducted as previously described. 25 RAFT polymer chain extension was conducted in dioxane under nitrogen with the NAM and DMA monomers (1.5 M), selecting a degree of polymerisation (DP) of 300; using ACVA (10 mg mL −1 stock in dioxane) as the initiator and keeping the CTA to initiator ratio as 2. The reaction was left to stir under nitrogen at 70 °C for 24 h. The resulting polymers (NAM 150 -(HDD-PIP)-NAM 150 and DMA 150 -(HDD-PIP)-DMA 150 ) were analysed using 1 H NMR and SEC.…”

“…To address this our group recently reported a grafting-from methodology for PBAE post-synthetic functionalisation with RAFT polymers, enabling the synthesis of a diverse range of ABA triblock copolymer scaffolds. 25…”