Soft Mesoporous Organosilica Nanoplatforms Improve Blood Circulation,Tumor Accumulation/Penetration,and Photodynamic Efficacy

To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared,denoted SMONs-HA-Cy5.5,and comparative studies between SMONs-HA-Cy5.5(24.2 MPa)and stiff counterparts(79.2 MPa)are conducted.Results indicate that,apart from exhibiting a twofold increase in tumor cellular uptake,the soft nanoplatforms also display a remarkable pharmacokinetic advantage,resulting in considerably improved tumor accumulation.Moreover,SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration,achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts.Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels,diffuse farther in the dense extracellular matrix,and reach deeper tumor tissues compared to the stiff ones.Specifically,the soft nanoplatforms generate a 16-fold improvement(43 vs.2.72μm)in diffusion distance in tumor parenchyma.Based on the significantly improved blood circulation and tumor accumulation/penetration,a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5.The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.

Mitochondria-targeted Janus mesoporous nanoplatform for tumor photodynamic therapy

Photodynamic therapy(PDT)is an effective treatment method for tumors.But the specifically accumulated of photosensitizer was very difficult in the tumor site,which greatly limited the efficacy of PDT.Here,mitochondria-targeted Janus mesoporous nanoplatform(JPMO-Pt-CTPP-ZnPc)for PDT was prepared,the nanoplatform has uniform size(275 nm)and good dispersion and biocompatibility.The confocal laser scanning microscopy(CLSM)revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells,and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc.This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform.In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser,and the survival rate of cells incubated with 60μg/mL JPMO-Pt-CTPP-ZnPc was only 3%.Simultaneously,compared with JPMO-Pt-ZnPc(not modified with mitochondria targeting molecules CTPP),the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better,as it has targeted mitochondria in cells.

Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections

The formation of bacterial biofilms closely associates with infectious diseases.Until now,precise diagnosis and effective treatment of bacterial biofilm infections are still in great need.Herein,a novel multifunctional theranostic nanoplatform based on MnO_(2)nanosheets(MnO_(2)NSs)has been designed to achieve pH-responsive dual-mode imaging and hypoxia-relief-enhanced antimicrobial photodynamic therapy(aPDT)of bacterial biofilm infections.In this study,MnO_(2)NSs were modified with bovine serum albumin(BSA)and polyethylene glycol(PEG)and then loaded with chlorin e_(6)(Ce_(6))as photosensitizer to form MnO_(2)-BSA/PEG-Ce_(6)nanosheets(MBP-Ce_(6)NSs).After being delivered into the bacterial biofilm-infected tissues,the MBP-Ce_(6)NSs could be decomposed in acidic biofilm microenvironment and release Ce_(6)with Mn^(2+),which subsequently activate both fluorescence(FL)and magnetic resonance(MR)signals for effective dual-mode FL/MR imaging of bacterial biofilm infections.Meanwhile,MnO_(2)could catalyze the decomposing of H2O_(2)in biofilm-infected tissues into O_(2)and relieve the hypoxic condition of biofilm,which significantly enhances the efficacy of aPDT.An in vitro study showed that MBP-Ce_(6)NSs could significantly reduce the number of methicillin-resistant Staphylococcus aureus(MRSA)in biofilms after 635nm laser irradiation.Guided by FL/MR imaging,MRSA biofilm-infected mice can be efficiently treated by MBP-Ce_(6)NSs-based aPDT.Overall,MBP-Ce_(6)NSs not only possess biofilm microenvironment-responsive dual-mode FL/MR imaging ability but also have significantly enhanced aPDT efficacy by relieving the hypoxia habitat of biofilm,which provides a promising theranostic nanoplatform for bacterial biofilm infections.

Computed tomography and photoacoustic imaging guided photodynamic therapy against breast cancer based on mesoporous platinum with insitu oxygen generation ability

Photodynamic therapy(PDT)has been widely used in cancer treatment.However,hypoxia in most solid tumors seriously restricts the efficacy of PDT.To improve the hypoxic microenvironment,we designed a novel mesoporous platinum(mPt)nanoplatform to catalyze hydrogen peroxide(H2 O2)within the tumor cells in situ without an extra enzyme.During the fabrication,the carboxy terminus of the photosensitizer chlorin e6(Ce6)was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol(SH-PEG-NH2)by a condensation reaction,and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH2.Material,cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H2 O2 to produce oxygen(O2)and that Ce6 transformed O2 to generate reactive oxygen species(ROS)upon laser irradiation.The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation.Due to the high atomic number and good near-infrared absorption for Pt,this Pt@PEG-Ce6 nanoplatform showed computed tomography(CT)and photoacoustic(PA)dual-mode imaging ability,thus providing an important tool for monitoring the tumor hypoxic microenvironment.Moreover,the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-la(HIF-1α)and programmed death-1(PD-1)in tumors,discussing the relationship between hypoxia,PD-1,and PDT for the first time.

Controlled PEGylation of periodic mesoporous organosilica nanospheres for improving their stability in physiological solutions

The stability of periodic mesoporous organosilica(PMO) nanoparticles in physiological solutions greatly affects their potential biomedical applications. Herein, thioether-bridged PMO nanospheres with a diameter of 61 nm are synthesized. Then, the thioether-bridged PMO nanospheres are modified with different molecular weighted polyethylene glycol(PEG) via click reaction for the first time. FI-IR and thermogravimetric analysis confirm the successful modification of PEG on the PMO. The influence of PEG molecular weight on the dispersity and stability of the PMO-PEG in phosphate buffer(PBS) and Dulbecco's modified Eagle's medium(DMEM) is studied. The results show that the PEG coating increases the stability and dispersity of PMO in the biological solutions. The PMO-PEG1K, PMO-PEG2K, and PMOPEG5K have better stability in PBS solution. The PMO-PEG2K shows best stability and dispersity in DMEM. Over all, this work provides important method and knowledge to guide the modification of PMO for biomedical

Deformable double-shelled hollow mesoporous organosilica nanocapsules:A multi-interfacial etching strategy

Multishelled hollow structures have drawn increasing interest because of their peculiar compartmentation environments and physicochemical properties.In this work,deformable double-shelled hollow mesoporous o rganosilica nanocapsules(DDHMONs)were succes s fully synthesized by a multi-interfacial etching strategy.The obtained DDHMONs have a double-shelled structure with aninorganic-organic hybrid framework,a uniform outer layer(~320 nm)and inner layer(~180 nm),ordered mesochannels(~2.21 nm),and a large specific surface area(~1233 m^(2)/g).In vitro toxicity tests show that the DDHMONs have excellent biocompatibility when coincubated with human breast cancer cells.In addition,the anti cancer substance doxorubicin(DOX)can be highly loaded in DDHMONs(~335μg/mg).The results from flow cytometry together with confocal laser scanning microscopy show that DOX can be efficiently delivered into MCF-7 cells by DDHMONs,thus improving chemotherapeutic efficiency and demonstrating that DDHMONs have potential nanomedicine applications as anticancer agents.

Uniform hierarchical silica film with perpendicular macroporous channels and accessible ordered mesopores for biomolecule separation

Herein, we demonstrate that silica films with perpendicular macroporous channels and accessible ordered mesopores can be conveniently prepared. The hierarchical macroporous–mesoporous silica films are synthesized by using zinc oxide nanorod array as macroporous template and CTAB surfactant as mesoporous template. In basic surfactant-containing solution, ordered mesoporous silica shells homogeneously grow on the zinc oxide nanorod array. The growth of the mesostructures do not require any chemical modification for the zinc oxide nanorod, which opens a new way for preparing hierarchical silica films with perpendicular mesochannels. The prepared hierarchical macroporous–mesoporous silica films possess a uniform thickness of 2μm, large perpendicular macropores with a length of 1.8μm and a width of 80 nm, and accessible ordered mesopores. Separation experiment demonstrates that this macroporous–mesoporous film can effectively separate biomolecules with different sizes.