Biodegradable magnesium ion-doped silica-based molecularly imprinted nanoparticles for targeting tumor cells to drugs controlled release and recognition mechanism research

Herein, we designed and constructed a novel biodegradable molecularly imprinted nanoparticles (Mg-SMSNs/DOX-Ce6 @MIPs) using a new degradable functional monomer prepared by glycerol and lactide, on magnesium ion-doped stellated mesoporous silica nanoparticles (Mg-SMSNs). These nanoparticles loaded with the anticancer drug doxorubicin (DOX) and chlorin e6 (Ce6) were used to target sialic acid (SA) overexpressed on the surface of tumor cells and release drugs in response to the tumor microenvironment. The molecularly imprinted layer avoided premature drug leakage, meanwhile, the large number of ester bonds contained in the functional monomers in the layer degraded by protonation in the tumor microenvironment to expose the drugs. Mg2+ doping in SMSNs enhanced the degradation performance in tumor microenvironment to achieve tumor-responsive drug release. The multifunctional monomers increased the interaction with SA, enhanced the binding force, and accurately targeted recognition was obtained. The recognition mechanism of Mg-SMSNs/DOX-Ce6 @MIPs to SA and drug release were investigated by model analysis. The cytotoxicity and cellular targeting of Mg-SMSNs/DOX-Ce6 @MIPs revealed that Mg-SMSNs/DOX-Ce6 @MIPs could specifically recognize SA to target MCF-7 tumor cells without interference. Under laser irradiation, Ce6 and DOX could achieve synergistic treatment to tumor cells. Mg-SMSNs/DOX-Ce6 @MIPs present good biological abilities in terms of active targeting, pH-responsiveness, antitumor efficiency and biocompatibility.