Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for doxorubicin on-demand delivery and reduced premature release.

Hybrid nanocarriers based on mesoporous silica nanoparticles (MSNs) and supported lipid bilayer (SLB) have been studied as drug delivery system. It still remains challenges to develop these nanocarriers (SLB-MSNs) with on-demand drug release profile for chemotherapy. Here, we reported the biocompatible SLB-MSNs with high drug loading, which could release doxorubicin (DOX) in response to hyperthermia and reduce premature release. After synthesis of MSNs via a sol-gel procedure, the thermo-responsive SLB was deposited on the MSNs by sonication to completely seal the mesopores. The obtained SLB-MSNs consisted of 50 nm-sized MSN cores and 6.3 nm-thick SLB shells. Due to the big surface and pore volume of MSNs, the high drug loading content (7.30±0.02%) and encapsulation efficiency (91.16±0.28%) were achieved. The SLB blocking the mesopores reduced 50% of premature release and achieved on-demand release in a thermo-responsive manner. Moreover, SLB-MSNs showed good hemocompatibility at any tested concentration (25-700μg/mL), while bare MSNs caused 100% of hemolysis at concentration larger than 325μg/mL. In addition, in vitro U251 cell uptake experiment demonstrated that compared with uncapped MSNs, SLB-MSNs could prevent untargeted cellular uptake of DOX owing to reduced premature release and steric hindrance of PEG, which would be beneficial to minimize toxicity for healthy tissues. These results indicated that SLB-MSNs with thermo-responsive release capacity possessed great potential in future synergistic thermo-chemotherapy.