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Supplementary MaterialsSC-006-C4SC03549F-s001. Furthermore, we proven targeted drug delivery and cellular imaging

Supplementary MaterialsSC-006-C4SC03549F-s001. Furthermore, we proven targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising 19F MRI-traceable drug carriers for application in cancer therapy and bio-imaging. Introduction Efficient delivery of drugs to diseased tissues is a major goal in the field of drug Regorafenib tyrosianse inhibitor delivery in an effort to reduce adverse effects.1 Toward this end, various nanoparticle-based drug carriers such as liposomes, polymers, and inorganic materials have been developed.2 Among these nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted significant attention owing to their attractive properties such as extremely large surface areas (1000 m2 gC1), tunable pore sizes (1.5C10 nm), and ease of functionalization various synthetic approaches.3 Since controlled release of drugs from the pores of MSNs results in prolonged drug efficacy, MSNs serve as ideal materials for drug delivery.4 To assess the drug efficacy and toxicity of drug carriers, it is essential to monitor the localization of the drug carrier. Accordingly, Modified with imaging agents have already been created MSNs. Fluorescence-traceable MSNs are of help for visualizing mobile localization fluorescence microscopy. Specifically, near infrared (NIR) fluorescent dye-modified MSNs are effective nanomaterials for visualization in cells and localization.5 Magnetic resonance imaging (MRI)-traceable MSNs also have attracted attention in neuro-scientific medication delivery due to their deep tissue imaging capabilities. MRI can be a noninvasive molecular imaging technique found in both Regorafenib tyrosianse inhibitor medical- and research-based areas.6 Gd3+ complex- or superparamagnetic iron oxide (SPIO)-loaded MSNs Regorafenib tyrosianse inhibitor are widely used due to their high sensitivity.7 Recently, multimodal imaging methods (NIR/MRI) possess gained attention as the mix of NIR and MRI provides detailed information concerning deep cells and cell localization.8 Therefore, MSNs that may be traced multiple methods (NIR/MRI) are desired. l9F MRI offers attracted significant interest due to the high level of sensitivity much like that of 1H and negligible history indicators.9 19F MRI compare agents are ideal for tracking specific biological makers.10 Although MSNs packed with 19F-traceable fluorine compounds have already been created, the fluorine-containing compounds can diffuse through the pores from the MSNs.11 On the other hand, perfluorocarbon (PFC)-encapsulated micelles have surfaced as highly delicate 19F MRI contrast agents and also have been used as cell-tracking markers.12 Although PFC encapsulated micelles with prospect of make use of in medication delivery have been reported,13 nanoparticles are not suitable for use as drug carriers owing to their low stability in aqueous solutions. Thus, MSNs with PFC-based cores are potentially viable for efficient drug delivery and as traceable drug carriers by 19F MRI. In a previous study, we developed novel, EBR2 highly sensitive 19F MRI contrast agents termed FLAME (FLuorine Accumulated silica nanoparticles for MRI Enhancement), composed of a PFC core and amorphous silica shell.14 FLAME has excellent properties such as high sensitivity, feasible surface modifications, and biocompatibility. Furthermore, we showed that FLAME was useful for cell labeling and tumor imaging. 14 In this study, by advancing the silica coverage of the PFC core, we developed 19F MRI traceable MSNs as drug carriers. The MSNs consisted of the PFC core and an NIR dye modified-mesoporous silica shell, enabling both dual modal imaging (NIR/19F MRI) and drug delivery. The modification of targeting ligands on the MSN surface enhanced the internalization of the MSNs into tumor cells, resulting in adequate drug efficacy due to fast drug release in acidic environments. Results and discussion Design, preparation, and physical properties of 19F MRI- and fluorescence-traceable drug delivery carrier For efficient drug delivery and monitoring of drug carriers, we designed a novel drug carrier with dual modal imaging capabilities (NIR/19F MRI), termed mFLAME (mesoporous FLAME, Fig. 1a). mFLAME consisted of a perfluoro-15-crown-5-ether (PFCE) core and mesoporous silica shell. PFCE is a highly sensitive 19F MRI marker owing to its twenty magnetically identical fluorine atoms.12 Mesoporous silica shells are stable in aqueous solutions, and drugs can be loaded into their pores. Furthermore, active targeting to foci can be achieved by modifying targeting ligands on the mFLAME surface. To impart fluorescence imaging capabilities, Cy5 dye was covalently modified on a mesoporous silica shell by silica polymerization in the presence of Cy5-conjugated 3-aminopropyltriethoxysilane (APTES). Open in a separate window Fig. 1 (a) The components of mFLAME. (b) Transmission electron microscopy (TEM) image of mFLAME. (c) N2 adsorption/desorption isotherms of mFLAME. (d) Excitation and fluorescence spectra of mFLAME in phosphate buffered saline (pH 7.4). (e) (Left) 19F MRI of mFLAME in phosphate buffered saline (500 L); (right) plot of normalized 19F MRI signal intensity.