Tumor Microenvironment Activated Multifunctional Nanomaterials For Precisely Controlled Tumor Photothermal And Photodynamic Therapy

Cancer,as one of the leading causes of death in the world,is a serious threat to human health.Although surgical excision,chemotherapy and radiation therapy play an important role in the treatment of cancer,there are some limitations in these treatments that can not meet the needs of human beings.In recent years,the development of nanotechnology has provided more strategies for tumor treatment.Light-induced photothermal therapy and photodynamic therapy are highly specific.After administration of therapeutic agents,heat or reactive oxygen species(ROS)can be produced upon irradiation with additional light source to treat the tumor.Therefore,photothermal therapy and photodynamic therapy have great potential in the treatment of cancer.In addition many photothermal conversion reagents and photosensitizers have been developed.Based on these findings,the combination of photothermal and photodynamic therapy could generate the higher therapeutic efficiency.But there are still some problems that hinder the extensive application of this combination therapy.First of all,it is very difficult to control the gathering of photothermal conversion reagents only at tumor site.Meanwhile,there is no guarantee that the light source will only be irradiated at the tumor site,which will cause high temperature and damage to the normal tissue.Secondly,two light sources with different wavelengths are usually employed to trigger photothermal therapy and photodynamic therapy.This complicated cancer treatment may weaken the therapeutic effect.In order to solve these two problems,an ideal therapeutic platform that not only improves the therapeutic effect,but also protects normal tissues is needed.Therefore,only single light source to activate the photothermal reagents and photosensitizers to produce heat and ROS simultaneously are pretty important to improve the therapeutic effect.Herein,a double therapeutic model system by combining photothermal with photodynamic therapy was developed using polyaniline(PANI)as pH response photothermal conversion reagent and indocyanine green(ICG)as photosensitizer.The nanoplatform was constructed by synthesizing polyaniline in hollow mesoporous silica(HMSN)and absorbing small molecule photosensitizer ICG.In order to increase the biocompatibility and safety of the platform,hyaluronic acid(HA)is adsorbed on the outermost layer of the material by electrostatic adsorption.The synthesized nanomaterials can produce both heat and ROS under laser irradiation at 808 nm.The experimental results show that the HMSN@PANI/ICG/HA can be synthesized quickly and effectively.And data on cell level and animal level shows that the material has no obvious toxicity and exhibits good photothermal conversion ability under the stimulation of acidic environment.The drug was administered by tail vein injection.HMSN@PANI/ICG/HA can be enriched in tumor site through EPR effect and can effectively produce heat and ROS under 808 nm near infrared laser irradiation to inhibit the growth of tumor in mice.