Effects of Muco-inert and Acid-sensitive Modification on Mucosal Penetration of Nanoparticles br

Gastric cancer???cervical carcinoma???lung cancer are occurred in mucosa???and the nanoparticles provideda competitive way for the diagnosis and therapy of these diseases.However???the mucus layer which contains mucusand other viscous substances could adsorb and remove the foreign substance???resulting the hindered penetration ofnanoparticles.In this paper???a pH-responsive mucus-inert nanoparticle was designed for penetrating mucus andentering mucosal epithelial cells.In brief???mesoporous silica nanoparticles with surface amination???MSNs-NH2???was prepared by sol-gel method.Then???the zwitterionic polymer was modified to the surface of MSNs-NH2by atom transferradical polymerization to form mucus-inert particles???MSNs-pCBMA???.Acid-sensitive molecule DMMA was modifiedonto MSNs-pCBMA through amino groups on the particle surface to obtain pH-responsive mucus-inert nanoparticles???MSNs-pCBMA-DMMA???.The results of transmission electron microscopy???TEM??????proton nuclear magnetic resonance???1H NMR??????Fourier transform infrared spectrophotometer???FTIR???andZetapotential measurements showed that fournanoparticles were synthesized successfully???and MSNs-pCBMA-DMMA exhibited sensitive pH response at pH=7.4-5.7.A mucus-containing Transwell (R) model was used to study the permeability of nanoparticles in mucus.Thepenetration results showed that within4h???the mucus permeability of MSNs-pCBMA-DMMA reached16.3%???1.9times that of MSNs-pCBMA and3times that of MSNs-NH2???and its relative apparent permeability coefficient reached2.96calculated with the apparent penetration coefficient???Papp???of MSNs-NH2as the reference.In addition???thegrafting pCBMA improved the penetration rate of nanoparticles in mucus and the modification of DMMA furtherimproved the penetration rate.Cytotoxic test showed that the viability of cells cultured with100 mu g/mL MSNs-pCBMA-DMMA was78.3% in24h???indicating its good biosafety.The cellular uptake experiment showed that MSNs-pCBMA-DMMA could be endocytosed effectively at4h???and exhibited better endocytosis performance compared withother particles.The work proved that the combination of mucus inertia and acid sensitivity can effectively promote themucosal permeability of nanoparticles???and MSNs-pCBMA-DMMA has excellent mucus permeability.The experimen???tal results would benefit the design of nanoparticles for the diagnosis and therapy of mucosal diseases