Construction Of Upconversion Nanocrystals-based Nanocarriers For Photodynamic Therapy

Photodynamic therapy（PDT）is a new method for the treatment of malignant tumor.However,traditional PDT in deep tissue is mainly constrained by the poor solubility of photosensitizers and limited tissue-penetration of excitation light.The emerging of nano drug delivery system,provides an effective way to solve the problem of poor solubility of therapeutic drugs.Among most of the nanocarriers,upconversion nanoparticles（UCNs）,which absorbs the near-infrared（NIR）light and convert it into UV and visible light,can effectively improve the tissue penetration depth of the excitation light.Herein,based on the UCNs,by polymer and mesoporous silica modification,two kinds of UCNs-based nano delivery systems were constructed for PDT treatment in deep-tumor therapy.The details are as follows:1.The synthesis of drug loaded upconversion nanocarriers（ZnPc loaded-UCN@lipid@polymersome NPs）and their application in PDT.The hydrophobic UCNs were transferred into water by an amphiphilic lipid named octadecyl-quaternized poly-glutamicacid.Polystyrene-block-poly（acrylic acid）was selected to form the big polymeric polymersome container to carry photosensitizers and UCNs,thus forming a multi-functional drug delivery system with good chemical stability and high drug loading efficiency.The results showed that the nanoparticles were uniform and dispersed as individuals.Under the exposure of the 980 nm NIR light,they could generated cytotoxic produce reactive oxygen species（ROS）for PDT.Meanwhile,the fluorescent emitting from the UCNs could be used for tumor cell imaging.In addition,RGD peptide decoration enhanced target specificity of the nanparticles to cancer cells.2.Based on UCNs,the light-triggered drug delivery system（Dox loaded-UCN@mSiO₂-（Azo+RB）NPs）was developed for combinational therapy by using（NaYF₄:Yb,Tm）@0.6（NaYF₄:Yb,Er）UCNs as inner core,doxorubicin（Dox）as antitumor drugs,and mesoporous silica as the firm framework for loading drugs,as well as covalently incorporating the photosensitizers Rose Bengal（RB）and photoresponsive azobenzene groups（Azo）,the NIR light-triggered co-release of Dox and ROS nanosystem was constructed successfully.The results showed that the nanoparticles were uniform and monodisperse with an average diameter of about 70 nm Upon irradiation,the green emission from UCNs could be absorbed by photosensitizers to produce cytotoxic ROS for PDT.Meanwhile,the UV/blue emission could be used for triggering the trans-cis-trans isomerization of the Azo molecules,and the continuous rotation–inversion movement propelled the release of therapeutic agents,simultaneously realizing chemotherapy and PDT to kill the cancer cells.Compared with single chemotherapy or PDT therapy systems,the synergistic therapy based on the UCNs nanosystem demonstrated significantly enhanced can tumor cell killing efficiency.Taken together,two kinds of UCNs-based multifunctional nanoplatforms for tumor diagnosis and therapy were designed and synthesized in this article.All the results demonstrated that they hold great potential in the field of tumor theranostics.