Disulfide-Functionalized Unimolecular Micelles as Selective Redox-Responsive Nanocarriers

Abstract

Redox-sensitive hyperbranched dendritic-linear polymers (HBDLPs) were prepared and stabilized individually as unimolecular micelles with diameters in the range 25-40 nm. The high molecular weight (500-950 kDa), core-shell amphiphilic structures were synthesized through a combination of self-condensing vinyl copolymerization (SCVCP) and atom transfer radical polymerization (ATRP). Cleavable disulfide bonds were introduced, either in the backbone, or in pendant groups, of the hyperbranched core of the HBDLPs. By triggered reductive degradation, the HBDLPs showed up to a 7-fold decrease in molecular weight, and the extent of degradation was tuned by the amount of incorporated disulfides. The HBDLP with pendant disulfide-linked functionalities in the hyperbranched core was readily postfunctionalized with a hydrophobic dye, as a mimic for a drug. An instant release of the dye was observed as a response to a reductive environment similar to the one present intracellularly. The proposed strategy shows a facile route to highly stable unimolecular micelles, which attractively exhibit redox-responsive degradation and cargo release properties.

Synthesis of Unimolecular Micelles with Incorporated Hyperbranched Boltorn H30 Polyester modified with Hyperbranched Helical Poly(phenyl isocyanide) Chains and their Enantioselective Crystallization Performance

“…However, although the polymeric micelles with excellent structural stability were achieved, sophisticated chemical reactions and postmodification were always needed. Alternatively, unimolecular micelles referring to nanostructures with polymer chains covalently anchored to a dendritic or hyperbranched core is a new type core–shell structure, whose tight covalent linkage endows them excellent disperse dimensions and structural integrity, and therefore avoids the premature disintegration once subjected to high dilution. As a unique member in the family of hyperbranched polyester, commercially available Boltorn H20, H30, and H40 were widely utilized to construct unimolecular micelles and play an important role in several fields due to the predetermined core size, controllable length, density of grafted chains, as well as their biodegradability and biocompatibility .…”

A review on core–shell structured unimolecular nanoparticles for biomedical applications

“…In the acidic endocytic compartments, the imine linkers were cleaved quickly, thereby causing a more rapid drug (DOX) release, and subsequently leading to a better therapeutic efficacy compared to unimolecular micelles lacking a pH-responsive drug release profile in A549 lung cancer cells. Since the concentration of glutathione (GSH) (approximately 2–10 mM) is drastically higher than in the extracellular spaces (approximately 2–20 μM) [161–163], GSH-responsive unimolecular micelles for redox-responsive drug release have also been reported [96, 164, 165].…”

Synthesis of branched polyisobutylenes via cationic copolymerization of p‐chloromethylstyrene and isobutylene

“…[4][5][6] Monomers, oligomers, and formed polymer chains randomly react with each other to form macromolecules with the increase of conversion; This inherent uncontrolled step-growth and nonspecific initiation result in polymers with polydisperse and irregularly branched structures. [7][8][9] To attain a narrow dispersion and well-defined structure, various approaches have been developed, such as slowing the addition of monomers into a dilute solution of multifunctional core [10][11][12][13] and segregating the polymerization of monomers in a confined nanospace. 14,15 Some new techniques have recently been developed, for example by designing a monomer AB* with a hierarchical reactivity, where B* only participates in polymerization after A has been consumed.…”

“…To attain a narrow dispersion and well‐defined structure, various approaches have been developed, such as slowing the addition of monomers into a dilute solution of multifunctional core 10–13 and segregating the polymerization of monomers in a confined nanospace 14,15 . Some new techniques have recently been developed, for example by designing a monomer AB* with a hierarchical reactivity, where B* only participates in polymerization after A has been consumed 16,17 .…”