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

Metal-free elementary nanomaterials, having low toxicity and excellent stability, are considered to be next-generation green materials. In particular, the hollow hierarchical metal-free substances, possessing good porosity and a desired specific surface area, will undoubtedly be the alternative nanomaterials for biomedical applications in future. Herein, we first proposed a facile cell-regulated strategy for the construction of hollow sulfur nanospheres (HSNSs) with porous shell. In this biomimetic strategy, the precursor Na2Sx generates HSNSs according to the disproportional reaction by exploiting the cellular acid microenvironment cleverly. The yeast cell-derived biomolecules, as regulators and stabilizers, play a critical role in the construction of HSNSs with favorable water dispersibility and biocompatibility. Under the mediation of yeast cells, the self-assembly of S nanoparticles results in sufficient internal space and permeable shell of HSNSs, which endow them with not only excellent drug loading efficiency but also good performance in the sustained release of the drug due to the classic pore-by-pore diffusion pattern. In addition, depending on the targeted modification with folic acid and the inherent pH-dependent property of doxorubicin hydrochloride (DOX) release under the acidic tumor microenvironment, these synthesized HSNSs have been proved to be an efficient dual-responsive drug delivery system.