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Miktoarm Star Polymers with Environment‐Selective ROS/GSH Responsive Locations: From Modular Synthesis to Tuned Drug Release through Micellar Partial Corona Shedding and/or Core Disassembly
Author(s) -
Lotocki Victor,
Yazdani Hossein,
Zhang Qiaochu,
Gran Evan Rizzel,
Nyrko Anastasiia,
Maysinger Dusica,
Kakkar Ashok
Publication year - 2021
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.202000305
Subject(s) - nanocarriers , micelle , glutathione , reactive oxygen species , chemistry , amphiphile , drug delivery , biophysics , nanoparticle , nanotechnology , polymer , combinatorial chemistry , chemical engineering , materials science , organic chemistry , aqueous solution , copolymer , biochemistry , engineering , biology , enzyme
Branched architectures with asymmetric polymeric arms provide an advantageous platform for the construction of tailored nanocarriers for therapeutic interventions. Simple and adaptable synthetic methodologies to amphiphilic miktoarm star polymers have been developed in which spatial location of reactive oxygen species (ROS) and glutathione (GSH) responsive entities is articulated to be on the corona shell surface or inside the core. The design of such architectures is facilitated through versatile building blocks and selected combinations of ring‐opening polymerization, Steglich esterification, and alkyne‐azide click reactions. Soft nanoparticles from aqueous self‐assembly of these stimuli responsive miktoarm stars have low critical micelle concentrations and high drug loading efficiencies. Partial corona shedding upon response to ROS is accompanied by an increase in drug release, without significant changes to overall micelle morphology. The location of the GSH responsive unit at the core leads to micelle disassembly and complete drug release. Curcumin loaded soft nanoparticles show higher efficiencies in preventing ROS generation in extracellular and cellular environments, and in ROS scavenging in human glioblastoma cells. The ease in synthetic elaboration and an understanding of structure‐property relationships in stimuli responsive nanoparticles offer a facile venue for well‐controlled drug delivery, based on the extra‐ and intracellular concentrations of ROS and GSH.