Bubble-generated Mesoporous Silicon Nanocarriers For Targeted Combination Therapy Of Tumors

Malignant tumor is one of the most important factors which is influencing human's health negatively.Traditional single therapies have several obvious drawbacks and thus treatment effects are not satisfactory.For example,common chemotherapy is not ideal for the variety and complexity of malignant tumors,which may lead to multi-drug resistance.In recent years,photodynamic and photothermal therapy is not effective to treat metastatic tumors and the light source penetration is poor.Under these circumstances,treating malignant tumor has become a hot field of research.However,combinational therapy usually utilizes multiple treatment methods to constrict tumor growth and induce cells apoptosis,and achieve the effect of 1+1>2.Combinational therapy for cancer treatment has gotten much attention due to its special merits.In this paper,the research is divided into two parts:1.Constructing a kind of bubble-generating mesoporous silicon nanocarriers by utilizing a kind of inorganic materials-mesoporous silica which owns good biocompatibility to load doxorubicin(DOX)and bubble-generation compound ammonium bicarbonate in pores.And the nanoparticles were modified with pH-sensitive polydopamine.Photosensitizer indocyanine green(ICG)was eventually absorbed onto the polydopamine layer so as to conduct chemotherapy,photothermal and photodynamic therapy.We also modified the nanoparticles with hydrophilic polyethylene glycol(PEG)and targeting peptide arginine-glycine-aspartic acid(RGD)in order to improve stability and targeting effect.The physical and chemical properties of nanoparticles,such as surface morphology,particle size potential,photothermal and photodynamic effect,drug release in vitro,cellular uptake and generation of reactive oxygen species(ROS),were also studied and characterized.2.The distribution and accumulation of nanoparticles in main organs and tumor sites in mice,photothermal and photodynamic effect in tumor sites,killing effect of nanoparticles for tumor cells,tumor growth inhibition experiment and biological safety were studied.The results of size and potential indicate that nanoparticles have small size and outstanding stabilization.The result of drug release experiment in vitro shows this kind of nanocarrier is pH-responsive.In an acidic environment,the polydopamine layer could be destroyed and DOX was able to release from nanoparticles and to function.In addition,Ammonium bicarbonate would decompose into carbon dioxide(C02)bubbles that could destroy polydopamine layers and accelerate drug release for chemotherapy.The distribution of nanoparticles in the main organs and tumor sites of mice shows that nanocarriers could accumulate in tumor sites through blood circulation and would not accumulate in vivo for a long period.In vivo photothermal and photodynamic effect experiment results indicate nanoparticles could generate reactive oxygen species(ROS)in tumor sites and the temperature of tumor sites could also increase performed by nanoparticles under near infrared laser irradiation.In the experiment of tumor growth inhibition,the nano-carrier can effectively inhibit tumor growth.There is no significant damage to normal tissues during the treatment.This kind of bubble-generated mesoporous silicon nanoparticles can effectively inhibit tumor growth by combination therapy and has a broad application prospect in clinical medicine.