Regulation Of The Size,Structure And Function Of Mesoporous Organosilica Nanospheres And Their Biological Behavior

Mesoporous organosilica nanospheres?MONs?are a new kind of material that combine the characteristics of mesoporous silica nanospheres?MSNs?and organic groups.They possess controllable size,good dispersion,large specific surface area,and biological safety,demonstrating great application prospects in biomedicine.This thesis is guided by biomedical applications,focusing on the size,structure,function regulation and biological behavior of MONs.It mainly includes the following three aspects of work:1.Size effect of mesoporous organosilica nanoparticles on tumor penetration and accumulationThe size effect of mesoporous organosilica nanoparticles?MONs?on tumor penetration and accumulation remains poorly understood.In this section,we constructed the MONs of different sizes?20,40,60,and 100 nm?and systematically studied the biocompatibility of MONs in vivo through hematology,serum biochemical indicators,and histopathology,indicating that these four different sizes MONs had good biological safety.In the multicellular spheroids?MCSs?,20 nm MONs showed the deepest penetration depth.Quantitative analysis of the penetration depth of MCSs at 120?m using laser confocal scanning microscope?CLSM?Z-scan showed that the accumulation of MONs at 20,40and 60 nm were 3.6,2.6 and 1.9 times that of 100 nm MONs,respectively.After 24 hours of intravenous injection of MONs,the distribution of fluorescence in various organs showed that MONs mainly existed in liver,spleen and lung.The accumulation of MONs at 20,40 and 60 nm in tumors were 3.7,4.2 and 2.4 times that of 100 nm MONs separately.Tumor cryosections showed that the penetration depth of MONs at 20,40,and 60 nm were 30.7,19.6,and 2.6 times that of MONs at 100nm,respectively.2.General and facile syntheses of hybridized deformable hollow mesoporous organosilica nanocapsules for drug deliveryDeformable nanocapsules can significantly improve cellular uptake and enrichment of nanocapsules in tumors,our group has reported that the deformable mesoporous organosilica nanocapsules synthesized by preferential etching with only one organic component incorporated,but a single organic component will limit its application.In this part,we changed the introduction of organosilica precursors based on the principle of chemical homology,and successfully synthesized double-,triple-,and quadruple-hybridized deformable organosilica nanocapsules?DMONs?.The triple-hybridized DMONs possessed uniform and controllable diameters?100-330 nm?,thin shells?10-30 nm?,high surface areas(521-1000 m² g^-1),large hollow cavities?50-270 nm?,and good biocompatibility.When the number of nanospheres added was 1.25×10⁴,the uptake of DMONs by MCF-7 cells was 6 times that of MONs.The triple-hybridized DMONs incorporated with benzene groups possessed a high paclitaxel?PTX?loading capacity?16.9 wt%?because the?-?interactions between the drug and the framework.In addition,the DOX release behavior from DMONs/DOX was responsive to the glutathione?GSH?due to the incorporated thioether groups,which led to a high tumor cell killing effect.3.Mesoporous organosilica nanospheres in situ loading gadolinium oxide and its application in tumor magnetic resonance imaging and targeted drug deliveryThe nanoplatform that integrates diagnostic and therapeutic functions has broad clinical transformation prospects,the small size of Gd₂O₃ can be used as a highly sensitive magnetic resonance contrast agent.But due to its lack of targeting,the tumor accumulation is low,which is not conducive to imaging in the tumor area.In this part,we first prepared Gd₂O₃ in the MONs cavity by chemical deposition?Gd₂O₃@MONs?,modified the targeting peptide RGD and the fluorescent dye FITC on the surface of MONs?Gd₂O₃@MONs-FRGD?,and then loaded the drug DOX in the channel,the obtained Gd₂O₃@MONs-FRGD/DOX possessed high magnetic resonance imaging?MRI?and fluorescent imaging.The size of the prepared Gd₂O₃@MONs was about 80 nm,which had good dispersion and high longitudinal relaxation(19.38 m M^-1 s^-1).The blood routine and tissue sections of mice after intravenous injection of Gd₂O₃@MONs showed that Gd₂O₃@MONs had good biocompatibility.Cell uptake experiments showed that RGD modification significantly increased the uptake of Gd₂O₃@MONs-FRGD from 4T1 cells.After 24 hours of intravenous injection of Gd₂O₃@MONs-FRGD or Gd₂O₃@MONs-FITC in tumor-bearing mice,fluorescence imaging and tissue frozen sections showed that Gd₂O₃@MONs-FRGD and Gd₂O₃@MONs-FITC were mainly distributed in the liver and lung,and in the heart and kidney was extremely low.The accumulation of Gd₂O₃@MONs-FRGD in the tumor was twice that of Gd₂O₃@MONs-FITC,and more obvious contrast enhancement T₁-weighted magnetic resonance image.Frozen sections of tumor tissue showed that Gd₂O₃@MONs-FRGD had stronger penetration and accumulation capacity than Gd₂O₃@MONs-FITC.In addition,Gd₂O₃@MONs-FRGD/DOX showed a good killing effect on tumour cells.