Preliminary Investigation On Charge-conversional Hollow Mesoporous Silica Nanoparticles Based Drug Delivery System

In recent years,nanoparticles based controlled drug release systems demonstrated great potential for tumor therapy,for instance,mesoporous silica nanoparticles,upconversion nanoparticles,gold nanoparticles and polymer micelle nanoparticales etc,which attracting scientists much attentions.However,these systems suffered some drawbacks,such as poor biocompatibility,severe toxic side effects,lack of dimesion uniformity,easy to leak drug during circulation etc.Thus,it is urgent to develop new controlled drug release system.To address above problems,we designed and fabricated one kind of pH responsive charge-conversional controlled drug release system,which employing hollow mesoporous silica nanoparticles as drug carrier and 2,3-dimethyl maleic anhydride modified chitosan as plugging agent,denoting as HMSNs-DMA-CS.Hollow mesoporous silica nanoparticles have relatively high pore volume and surface area,homogeneous and tunable size,and easy to be surface functionalization,which were used as carriers to load doxorubicin(DOX).Chitosan has excellent biocompatibility and could be degraded by lysozyme in a host.Dynamic light scattering analysis showed that the particle sizes of HMSNs-DMA-CS remained stable under physiological serum condition of pH 7.4.Zeta potential analysis showed that the nanoparticles were negatively charged.Nevertheless,when exposing the system to acid condition pH 6.5,mimicking tumor microenvironment,the particle sizes of HMSNs-DMA-CS dramatically decreased and their surface charges were conversed from negative to positive,which would be beneficial for in situ drug release at the tumor site.In order to validate the feasibility of the HMSNs-DMA-CS nanoparticles for controlled drug release,we employed HepG2 cell model,and co-incubated them with DOX loading HMSNs-DMA-CS nanoparticles(HMSNs-DMA-CS@DOX).Confocal laser scanning microscopy observation and flow cytometry analysis showed that HMSNs-DMA-CS@DOX nanoparticles could be endocytosed much more by HepG2 cells under weak acid condition of pH 6.5.HMSNs-DMA-CS nanoparticles were mainly distributed in cytoplasm and could efficiently induce tomor cells apoptosis.