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.

Development of phosphonate-terminated magnetic mesoporous silica nanoparticles for pH-controlled release of doxorubicin and improved tumor accumulation

In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on to the surface of MMSNs.The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer(VSM).pMMSNs had a spherical morphology and a pore size of 2.2 nm.FromN2 adsorption-desorption analysis,pMMSNs had a surface area of 613.4 m^(2)/g and a pore volume of 0.78 cm^(3)/g.Phosphonate modification improved the colloidal stability of MMSNs,and the hydrodynamic diameter of pMMSNs was around 175 nm.The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs.In addition,the rate and amount of release of doxorubicin(DOX)from DOX/pMMSNs was pH-dependent and increased with the decrease of pH.At pH 7.4,the release amount was quite low and only approximately 17wt%ofDOXwasreleasedin48h.AtpH5.0and3.0,the release rate increased significantly and the release amount achieved 31 wt%and 60 wt%in 48 h,respectively.To evaluate the magnetic targeting performance ofpMMSNs,FITC labeledpMMSNswas injected into mice bearing S180 solid tumor.FITC labeledpMMSNscontrolled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.

Co-solvent polarity controlled self-assembly of tetraphenylethylene-buried amphiphile for size-regulated tumor accumulation

We report that the co-solvent polarity can precisely control the TPE-buried amphiphile 1 to selfassemble into nanoparticles(NPs)in water with size range from21–32nm to 55–68nm to 95–106 nm.Excepted for size,these TPE-buried amphiphile fabricated NPs hold identical physical properties such as spherical shape,surface charge,and luminescent properties,and moreover,after covalent capture of the acrylate hydrophilic heads,the resulting cross-linked NPs(cNPs I–III)own excellent in vivo stability,which thus would be an ideal platform for investigating the size effects on tumor accumulation and penetration.