Cystamine-crosslinked and nanozyme decorated polyacrylic acid-based composite microgel of dual functionality: delivery and controlled doxorubicin release

Developing new and improving existing systems for controlled drug release is one of the top tasks of biomaterials science nowadays. The current work aims to develop an efficiently controlled doxorubicin release system based on composite hydrogel formed by polyacrylic acid p(AA) cross-linked by N,N’-bis(acryloyl)cystamine (BAC). The formed p(AA-BAC) microgel provides a dual function as a pH-sensitive doxorubicin holding carrier as well as an immobilization matrix for covalent bonding of gold nanoparticles (AuNPs) via sulfur groups of cystamine derivative cross-linker. The immobilized AuNPs are characterized by nanozyme (glucose oxidase-like) activity able to generate the local pH decrease via gluconic acid production in the presence of glucose as a trigger. The resulting local pH decrease provides protonation of carboxylic groups of the p(AA-BAC) matrix resulting in diminished electrostatic attraction between the carrier and the positively charged payload, thus causing its release from the microgels. The structural and morphological characterization of the proposed p(AA-BAC)-AuNPs composite microgel was performed by SEM, AFM, TEM, FTIR, and other techniques. The kinetics of the triggered release of the self-fluorescent doxorubicin was tested by fluorimetry combined with confocal fluorescent analysis. It was demonstrated that the proposed composite p(AA-BAC)-AuNPs microgel could be used as a promising smart release system for releasing a positively charged payload in response to a locally elevated glucose level.