Graphene oxide-templated biomineralization nanosystem enables multi-drug loading and controllable release

As a promising antitumor strategy, combination oncotherapy can achieve better therapeutic efficacy. However, given the different properties of drugs, carriers need to meet requirements for efficient encapsulation and controllable release of multi-drugs. Herein, we propose a graphene oxide (GO)-templated biomineralization nanosystem to optimize oncotherapy. For preparation, GO is conjugated with polyethylene glycol (PEG) to improve biostability, and glyeyrrhetinic acid (GA) is further grafted onto PEG chains for site-specific targeting. The generated nanosheet structure and large specific surface area support high doxorubicin (DOX) encapsulation and mineralized deposition of siRNA via π-π stacking and calcium phosphate co-precipitation, respectively. Followed by highly efficient penetration into tumor cells, GO-templated nanosystem performs swift drug release in response to tumor acidic microenvironment through dissolution of calcium phosphate and disruption of molecular interactions. After administration, the GO-templated nanosystem performs superior pharmacy properties and significant antitumor efficacy via the synergy of chemotherapy and RNA interference therapy. Collectively, a GO-templated biomineralization nanosystem provides an innovative delivery system for multi-drug administration in combinative tumor therapy.