Investigation Of Imaging-guided Tumor Theranostics Based On Rod-shaped Mesoporous Silica Nanocarriers

With the rapid development of nanoscience,nanotechnology has been applied in the field of biomedicine,including cancer prevention,diagnosis and treatment,which provides a new solution to overcome the bottleneck of cancer treatment.Photothermal therapy(PTT)is a spatiotemporal and non-invasive tumor treatment method,which utilize photothermal conversion agents(PTAs)to generate local hyperthermia under near-infrared(NIR)light irradiation almost without side effects on normal tissues.Compared with solo PTT,a strategy of combination with other treatment methods,including immunotherapy,photodynamic therapy(PDT)and radiotherapy(RT)exhibited dramatically improved therapeutic efficacy.Theranostics represent a method of combining biomedical imaging and cancer treatment,which could realize visual monitoring and precise treatment.Therefore,it is essential to rationally design a nanocomposite to integrate therapeutic and imaging constituents in one platform.However,the poor biocompatibility,low efficacy of drug loading and weak cellular uptake of nanocomposites heavily limit their bio-applications.Recently,mesoporous silica nanoparticles(MSNs)have been considered to be a promising nanoplatforms due to the adjustable sizes,large surface area,great modification capability,and good biocompatibility.Noticeably,it is reported that suitable aspect ratio and size of nanoparticles could increase the cellular uptake by the enhanced permeability and retention(EPR)effect.Therefore,rod-shape mesoporous silica nanoparticles(MSNRs)possesses higher cellular uptake efficiency,increasing the accumulation of therapeutic nanoparticles in tumor site and thus enhancing the anti-tumor efficacy.In addition,MSNRs have been studied as template to synthesize various rod-shape nano-agents.In view of these advantages of MSNRs mentioned above,two nanoplatforms were designed for tumor theranostic.Firstly,we constructed MoS₂nanosheets coated mesoporous silica nanorods(MSNR@MoS₂)via a one-step hydrothermal method,using silica nanorods as template,which could not only combine the MOST/CT imaging with PTT,but also improve the cellular uptake efficiency,thus enhancing the“specificity”of PTT.Human serum albumin(HSA),an active targeting-agents,was coated on MSNR@MoS₂ to promote bioavailability and reduce toxicity.Afterwards,the hydrophobic photosensitizer(PS),chlorin e6(Ce6)with fluorescence ability was chemically conjugated to MSNR@MoS₂-HSA to endow the nanocomposites with the ability of fluorescence(FL)imaging.TEM,UV-vis spectra,and XPS characterization have confirmed the successful preparation of MSNR@MoS₂-HSA/Ce6.In addition,in vitro performance test demonstrated that MSNR@MoS₂-HSA/Ce6 possessed outstanding photothermal conversion efficiency and ROS generation capacity.The FL/MOST/CT imaging capacity was also validated.The therapeutic efficacy was evaluated in cytological and animal experiments,which demonstrated that MSNR@MoS₂-HSA/Ce6 was an outstanding nanoplatform to effectively inhibit the tumor growth under the NIR irradiation.Based on the first study,we constructed a rod-shape biomimetic nanozymes for catalysis-enhanced PTT and RT against hypoxic tumor based on MSNR@Mn O₂-Au.Firstly,MSNR@Mn O₂ was prepared by hydrothermal method using MSNR as template.Then the ultra-small Au NPs were deposited on the surface of Mn O₂ by in-situ reduction method.In this nanocarrier,Mn O₂ could react with endogenous H₂O₂ to generate O₂ to alleviate tumor hypoxia,thus enhancing RT as well as providing p H responsive T₁-weighted MR imaging.At the same time,the ultra-small Au NPs can catalyze the oxidation of?-D-glucose to produce gluconic acid(H⁺)and H₂O₂,thus inhibiting the synthesis of heat shock protein(HSP)and reducing the thermotolerance of tumors.What's more,Au NPs also possessed excellent MSOT/CT imaging capacity.For characterization studies,TEM,UV-vis spectra,and XPS characterization were adopted to confirm the fabrication of MSNR@Mn O₂-Au.And the various performance test,including photothermal properties,O₂ generation capacity,MSOT/CT/MR imaging ability,hypoxia regulation and DNA damage in cell level,were evaluated.The therapeutic efficiency evaluation results demonstrated that MSNR@Mn O₂-Au performed excellent PTT/RT,exhibiting excellent anti-tumor efficiency.