New Design of Thiol‐Responsive Degradable Polylactide‐Based Block Copolymer Micelles

Abstract

A new design to synthesize thiol-responsive degradable polylactide (PLA)-based micelles having a disulfide linkage in the middle of triblock copolymers is reported. They were synthesized by a new method that centers on the use of a disulfide-labeled diol as an initiator for ring-opening polymerization, followed by controlled radical polymerization. These well-controlled copolymers with monomodal and narrow molecular weight distribution (M(w) /M(n) < 1.15) self-assembled to form aqueous micellar aggregates with disulfide-containing PLA cores, which is not toxic to cells. Central disulfide linkages were cleaved in response to thiols; such thiol-triggered degradation enhanced the release of encapsulated anticancer drugs.

<p>Multi-Stimuli-Responsive DOX Released from Magnetosome for Tumor Synergistic Theranostics</p>

“…For example, the PLA-based block copolymer composed of the disulfide linkages in the dual location positioned in the PLA core and PLA/POEOMA (polyoligoethylene oxide methacrylate) interface showed disassembly of micelles in the presence of 10 mM GSH after 20 h. 32 Amphiphilic block PLA-SS-POEOMA copolymers functionalized with disulfides at hydrophilic and hydrophobic block junctions degraded in the presence of DTT after 2 h. 6 Although SS(PLA- b -POEOMA) 2 bearing a single disulfide linkage in the middle of triblock copolymers did not exhibit a marked change in the dynamic particle size after 2 days with DTT, the molecular weight of the extracted residue evaluated by GPC was half that of the original. 33 This result suggests that the central single disulfide linkage of SS(PLA- b -POEOMA) 2 in the micellar core can be cleaved in response to DTT, to yield amphiphilic HS-PLA- b -POEOMA. Based on the studies of Oh and colleagues as well as our own previous studies, 1 polymers with disulfide linkages positioned in the central core of micelles exhibited a prolonged response to reducing agents.…”

Novel Temperature/Reduction Dual-Stimulus Responsive Triblock Copolymer [P(MEO2MA-co- OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] via a Combination of ROP and ATRP: Synthesis, Characterization and Application of Self-Assembled Micelles

“…Synthesis of OH-PLLA-SS-PLLA-OH used the method of ROP with L-lactide (LLA) as the polymeric raw material, 2,2'-dithio diethanol (SS-DOH) as the initiator, and Sn(Oct) 2 as the catalyst [43]. The specific synthesis route was as follows.…”

“…Synthesis of macromolecular initiator iBuBr-PLLA-SS-PLLA-iBuBr was performed by esterification reaction with dry triethylamine (TEA) as the acid-binding reagent, and 2-bromo-2-methylpropionyl bromide (Br-iBuBr) and purified homopolymers OH-PLLA-SS-PLLA-OH as reactants [43,44]. The specific synthesis route was as follows.…”

Thiol-responsive gemini poly(ethylene glycol)-poly(lactide) with a cystine disulfide spacer as an intracellular drug delivery nanocarrier

“…Therefore, polymeric micelles containing disulfide bonds have been prepared for redox-responsive drug delivery [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. These assemblies exhibit the controlled release of encapsulated drugs through the cleavage of disulfide bonds, causing destabilization or disintegration of the micellar aggregates.…”