Functional Rattle-type Hollow Mesoporous Silica For Molecular Detection And Drug Delivery

Rattle-type hollow mesoporous silica is a special type of core-shell structure and usually made up of three different components,namely core,void and shell.Just like many other silica nanomaterials,the hollow silica shows non-toxicity,high stability,good biocompatibility,easy surface modification.Besides,due to its special structure,it can also serve as universal drug carrier,sensitive nanosensor and stable catalytic nanoreactor.Now,nanomaterials with novel optical,electric,magnetic properties have been used as cores for optical imaging,magnetic guiding,metal catalysis.Furthermore,in combination with its good loading capability and smart drug releasing profile,many multi-functionalized nanocarriers and nanosensors have been developed.In this article,by taking advantages of the special core-shell structure,excellent drug loading capability and mature surface modification technique,we develop an excellent ratiometric fluorescent nanosensor for biosensing and imaging of bioactive small molecules,and a targeting delivery system for drug-resistant breast cancer therapy.The main contents are as follows:1.FITC Doped Rattle-type Silica Colloidal Particle-Based Ratiometric Fluorescent Sensor for Biosensing and Imaging of Superoxide AnionDue to the complicated surface modification process and background interference,applications of fluorescent nanosensor in practical biological samples are limited.Here,a simple,universal method was developed for ratiometric fluorescent determination of general small molecules.Taking superoxide anion(O2·-)as an example,the designed sensor was composed of three main moieties:probe carrier,rattle-type silica colloidal particles(mSiO2@hmSiO2 NPs);reference fluorophore doped into the core of NPs,fluorescein isothiocyanate(FITC);fluorescent probe for superoxide anion,hydroethidine(HE).In the absence of the sensor just emitted green fluorescence of FITC at 518 nm.When released HE was oxidized by O2·-,the oxidation product exhibited red fluorescence at 570 nm and the intensity was linearly associated with the concentration of O2·-,while that of reference element remained constant.Accordingly,ratiometric determination of O2·-was sensitively and selectively achieved with a linear range of 0.2-20 μM and the detection limit was calculated as low as 80 nM.Besides,the technique was also successfully applied for dual-emission imaging of O2·-in live cells and realized visual recognition with obvious fluorescence color change in normal condition or under oxidative stress.As long as appropriate reference dyes and sensing probes are selected,ratiometric biosensing and imaging of bioactive small molecules would be achieved.Therefore,the design could provide a simple,accurate,universal strategy for biological applications.2.Hyaluronidase-triggered Anticancer Drug and siRNA Delivery from Cascaded Targeting Nanoparticles for Drug-resistant Breast CancerMetastatic breast cancers over express connective tissue growth factor(CTGF),resulting in drug resistance and ineffective standard chemotherapy.Rattle-type hollow mesoporous silica(rmSiO2)was used for therapy of CTGF over-expressing breast cancer by co-embedding breast tumor homing cell-penetrating peptide(PEGA-pVEC)and hyaluronic acid(HA)as cascaded targeting media,as well as loading siRNA and anticancer drug in different locations simultaneously to overcome drug resistance.The cascaded targeting nanoparticles first selectively accumulated in the vasculatures under the guidance of PEGA-pVEC,cascaded by another targeting agent HA-mediated endocytosis,presenting greater in vivo tumor targeting ability than single targeting ligand vectors.In another sense,HA shell prevented the leakage of therapeutic drug during the cargo transport process,until the hyaluronidase(HAase)-triggered degradation upon entering lysosomes,guaranteeing controllable drug release inside the target cells.As protective shell disintegrated,siRNA was released into the cytoplasm to silence the gene associated with drug resistance,CTGF,thus facilitating the Dox-induced apoptosis.The cascaded targeting media(PEGA-pVEC,HA)advances the precision-guided therapy in vivo,while the encapsulation of siRNA into chemotherapy drug delivery system provides an efficient strategy for the treatment of drug-resistant cancers.