Self-assembled hydrogel nanocube for stimuli responsive drug delivery and tumor ablation by phototherapy against breast cancer

The shape and responsiveness of nanoengineered delivery carriers are crucial characteristics for the rapid and efficient delivery of therapeutics. We report on a novel type of micrometer-sized hydrogel particles of controlled shape with dual pH and redox sensitivity for intracellular delivery of anticancer drugs and phototherapy. The cubical HA-DOP-CS-PEG networks with disulfide links are obtained by cross-linking HA-DOP-CS-PEG with cystamine. The pH-triggered hydrogel swelling/shrinkage was not only affords effective doxorubicin release. It also actively provides the endosomal/lysosomal escape, redox-triggered drug release. The hydrogels degrade rapidly to low molecular weight chains in the presence of the typical intracellular concentration of glutathione. Drug-loaded cube particles found to be 12% more cytotoxic. ICG and DOX-loaded hydrogel cubes demonstrate 90% cytotoxicity when incubated with MCF-7 cancer cells for 24 and 48 h, respectively. This approach integrates the advantages of pH sensitivity, enzymatic degradation, and shape-regulated internalization for novel types of "intelligent" three-dimensional networks with programmable behavior for controlled delivery of therapeutics.