Ultrasound Triggered Drug Release By Aptamer Gated Hollow Mesoporous Silica Nanoparticles

PART I DESIGN CONSTRUCTION OF APTAMER GATED HOLLOW MESOPOROUS SILICA NANOPARTICLES AND CHARACTERISTIC STUDYObjective To prepare aptamer gated hollow mesoporous silica nanoparticles (HMSNs-Apt), and observe its physical characteristics and ultrasonic imaging in vitro, and to investigate the feasibility of being ultrasound Contrast agents.Methods Hollow mesoporous silica nanoparticles (HMSNs) were prepared by "structural difference-based selective etching" strategy. Based on carbodiimide technique, HMSNs-Apt were prepared. The morphology was observed under the transmission electron microscope (TEM) and the Scanning electron microscopy (SEM) respectively. The mean size and zeta potential were measured by a laser instrument. The chemical modification of the HMSN surface were observed by FITR. the US imaging examination was performed in different concentrations of HMSNs-Apt, different imaging mode and different Mechanical index, and the efficacy of the contrast agent for US imaging was evaluated by in vitro experiments.Results The freeze drying powder of HMSNs-Apt was white suspension in appearance with good redispersibility after adding with double distilled water or ethyl alcohol. It is spherical, with average particle size was (280.2±14.5) nm and potential was-(0.63±0.28) mV. The shell of HMSNs-Apt nanoparticles was more rough in TEM than HMSNs, and no obvious pore structure can be seen. The effect of the connect of HMSNs and aptamer was confirmed by FITR. The ultrasonic signal intensity enhanced with HMSNs-Apt concentrations increased in vitro, the CEUS also show similar results, and the ultrasonic signal intensity of CEUS enhanced with the mechanical index increased.Conclusion Aptamer gated hollow mesoporous silica nanoparticles which can act as a kind of ultrasonic contrast agent is successfully prepared, and it is regular, spherical, uniform and stable.PART II STUDY ON THE TARGETING AND DRUG RELEASING PERFORMANCE OF APTAMER GATED HOLLOW MESOPOROUS SILICA NANOPARTICLES IN VITROObjective To study the targeting performance of the aptamer gated hollow mesoporous silica nanoparticles,and to observe the effect of drug release by high intensity focused ultrasound (HIFU) triggering.Methods DOX was used as a model drug to loading in the HMSNs-Apt and HMSNs nanoparticles to be HMSNs-DOX-DNA and HMSNs-DOX. drug loading efficiency and encapsulation efficiency was evaluated. HMSNs-DOX and two HMSNs-DOX-DNA group was used in evaluating controlled drug releasing properties. One HMSNs-DOX-DNA group treated with HIFU, the other groups were control groups. Release curve was Drawed. HMSNs-Apt and HMSNs nanoparticles with DOX were marked as targeting group and non-targeting group. The targeting performance was verified by being incubated with human MCF-7 cells line in vitro.Results The result indicated that the responsive nanoparticle exhibited an excellent drug loading capacity and controlled drug releasing. After using HIFU, the release of the DOX enhanced obviously. In the targeted group, a lot of nanoparticles conjugated to MCF-7cells tightly, while little specific binding was found in the non-targeted group.Conclusion The HMSNs-Apt nanoparticles can targeted to MCF-7 cells specifically and effectively in vitro, which will hopefully become an ideal molecular probe for targeted imaging and treatment of Breast cancer.and, and the drug positioning release can markedly improved by HIFU in vitro.