Reductive Responsive Fluoroboron Dipyrrole/Mesoporous Silica Nanoparticles For Cancer Therapy

With the development of nanotechnology,nano drug delivery systems?NDDS?have received extensive attention.The NDDS can solve these problems of conventional chemotherapy such as poor water solubility,lack of targeting,and short cycle time to effectively improve anticancer efficacy and reduce side effect.The stimuli-responsive NDDS which can intelligently control drug release in response to the stimulation of the tumor microenvironment have been developed.In this thesis,we construct intelligent mesoporous silica nanoparticles?MSNs?-based NDDS for cancer therapy,in which the surface of MSNs was modified by fluoroboron compound BODIPY through reductive-responsive groups and the release of BODIPY could be controlled.1.Herein,we constructed reductive-responsive MSNs-I₂BDP-PEG nanoparticles for photodynamic therapy.First,the surface of MSNs was modified by iodide BODIPY via a disulfide bond.Then,MSNs-I2BDP was PEGylated to improve the water solubility and prolong the circulation time in vivo.The obtained MSNs-I₂BDP-PEG nanoparticles exhibited excellent stability with size of 90 nm measured by transmission electron microscope?TEM?.The experimental date indicated that MSNs-I₂BDP-PEG nanoparticles could be effectively endocytosed by tumor cells.Under the stimulation of intracellular higher glutathione,BODIPY could be released for photodynamic therapy due to the cleavage of disulfide bond.2.In this part,we decorate the surface of MSNs by one-pot Passerini reaction using near-infrared fluorescence BODIPY and poly?ethylene glycol?with an aldehyde group?PEG-CHO?.And doxorubicin?Dox?was loaded to achieve the release of the reduction response.The formed MSNs tactfully integrate chemotherapy,photothermal therapy and near-infrared fluorescence?NIRF?imaging.In vitro and vivo experiments substantiated the enhanced antitumor efficacy of multifunctional MSNs,indicating the significance of combination therapy integrating chemotherapy and photothermal therapy.These results attach importance to the potential of using multicomponent Passerini reaction to modify multifunctional MSNs and other nanoplatforms for theranostics.