Toward Intracellular\nDelivery: Aliphatic Polycarbonates\nwith Pendant Thiol-Reactive Thiosulfonates for Reversible Postpolymerization\nModification

Postpolymerization modifications are valuable techniques\nfor creating\nfunctional polymers that are challenging to synthesize directly. This\nstudy presents aliphatic polycarbonates with pendant thiol-reactive\ngroups for disulfide formation with mercaptans. The reductive responsive\nnature of this reaction allows for reversible postpolymerization modifications\non biodegradable scaffolds. Six-membered cyclic carbonate monomers\nwith pendant thiosulfonate groups were synthesized and polymerized\nusing controlled organocatalytic ring-opening polymerization, yielding\npolymers with narrow molecular weight dispersities (<i>Đ</i> = 1.2) and intact reactive thiosulfonate side chains. Reversible\nmodification with benzyl mercaptans achieved high degrees of disulfide\nmodification. Additionally, thiol-reactive carbonate monomers were\nblock-copolymerized onto polyethylene glycol (mPEG<sub>113</sub>)\nand then converted into benzyl disulfides, while the block copolymers’\nhydroxyl end groups remained available for fluorescent dye labeling.\nThe amphiphilic block copolymers self-assembled in water into micelles\n(∼33 nm diameter), capable of encapsulating hydrophobic molecules.\nThese micelles successfully delivered hydrophobic dyes into macrophages,\nindicating the potential for intracellular drug delivery.