Biodegradable Block Copolymer Micelles with Thiol-Responsive Sheddable Coronas

Abstract

Novel sheddable micelles having hydrophilic coronas capable of being shed from biodegradable polylactide (PLA) cores by the cleavage of disulfide linkages in response to thiols were prepared by aqueous micellization of PLA-based amphiphilic block copolymers functionalized with disulfides at block junctions. These well-defined copolymers were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization in the presence of a new disulfide-functionalized double-head initiator having both terminal OH and Br groups. (1)H NMR and GPC results indicate that both polymerizations were well-controlled with molecular weight distribution as low as M(w)/M(n) < 1.2. Aqueous micellization to form core/shell micelles with disulfides at the interface of PLA cores and hydrophilic coronas and their thiol-responsive degradation were investigated. In the presence of water-soluble thiols, disulfide linkages in the micelles were cleaved and hydrophilic coronas were lost, causing PLA cores to precipitate due to the loss of colloidal stability. In a biomedical perspective, the new sheddable micelles were not cytotoxic and hence biocompatible.

Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances

“…50 Moreover, diverse methodologies have been used for characterization of the thermoresponsive polymeric NPs such as cryogenic transmission electron microscopy (cryo-TEM), 51 atomic force microscopy (AFM), 52 nuclear magnetic resonance (NMR) spectroscopy, 53,54 small-angle X-ray scattering (SAXS), 51,55,56 Fourier-transform infrared spectroscopy (FT-IR), 10 UV–vis, 46 and static and/or dynamic light scattering (SLS/DLS). 46,57 …”

Neuron-Targeted Copolymers with Sheddable Shielding Blocks Synthesized Using a Reducible, RAFT-ATRP Double-Head Agent

“…The double-head agent CPADB-SS-iBuBr was synthesized by N , N ′-dicyclohexylcarbodiimide (DCC) coupling between the RAFT CTA 4-cyanopentanoic acid dithiobenzoate (CPADB) 7 and 2-hydroxyethyl-2′-(bromoisobutyryl)ethyl disulfide initiator (OH-SS-iBuBr) 8 in the presence of 4-(dimethylamino)pyridine (DMAP) as a catalyst. After purification by column chromatog-raphy, CPADB-SS-iBuBr was successfully obtained with 43.1% yield (Figure 1a).…”

“…Chain extension using different monomers by consecutive CLRP processes always leads to block copolymers with non-degradable C-C links in the block junctions. Recently Oh et al reported the synthesis of poly(lactide)-SS-polymethacrylate amphiphilic block copolymers with SS linkages positioned at the block junction by ring-opening polymerization (ROP) and ATRP, 8 but these methods are limited to the application of cyclic monomers.…”

Air‐Spun PLA Nanofibers Modified with Reductively Sheddable Hydrophilic Surfaces for Vascular Tissue Engineering: Synthesis and Surface Modification

“…The synthesis of HO‐ss‐Br double‐head initiator for both ROP and ATRP is described in our previous publication . In the presence of HO‐ss‐Br, a series of ROP of d,l ‐lactide (LA) mediated with tin(II) 2‐ethylhexanoate (Sn(Oct) 2 ) in toluene at 120 °C was conducted.…”