Cell-Regulated Hollow Sulfur Nanospheres with Porous Shell: A Dual-Responsive Carrier for Sustained Drug Release

Metal-free elementary nanomaterials, having low toxicity and excellentstability, are considered to be next-generation green materials. In particular, the hollowhierarchical metal-free substances, possessing good porosity and a desired specificsurface area, will undoubtedly be the alternative nanomaterials for biomedicalapplications in future. Herein, wefirst proposed a facile cell-regulated strategy for theconstruction of hollow sulfur nanospheres (HSNSs) with porous shell. In thisbiomimetic strategy, the precursor Na2Sxgenerates HSNSs according to thedisproportional reaction by exploiting the cellular acid microenvironment cleverly.The yeast cell-derived biomolecules, as regulators and stabilizers, play a critical role inthe construction of HSNSs with favorable water dispersibility and biocompatibility.Under the mediation of yeast cells, the self-assembly of S nanoparticles results insufficient internal space and permeable shell of HSNSs, which endow them with notonly excellent drug loading efficiency but also good performance in the sustainedrelease of the drug due to the classic pore-by-pore diffusion pattern. In addition, depending on the targeted modification with folicacid and the inherent pH-dependent property of doxorubicin hydrochloride (DOX) release under the acidic tumormicroenvironment, these synthesized HSNSs have been proved to be an efficient dual-responsive drug delivery system