Tumor Antigen Mediated Conformational Changes ofNanoplatform for Activated Photodynamic Therapy

【作者】Junjie Liu, Yiwen Zhang, Wei Liu, Kaixiang Zhang, Jinjin Shi, and Zhenzhong Zhang

【期刊名】Advanced Healthcare Materials

【影响因子】 2019年:6.357

【作者单位】School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2019, 1900791

【关键词】aptamers, conformational changes, PDT, switch-on, tumor antigens

【摘要】Photodynamic therapy (PDT) is a noninvasive powerful tool for tumor treatment. However, phototoxicity seriously limits the clinical application ofPDT, and activated PDT specifically response to tumor cell antigen is rarelyreported. Herein, a tumor cell specific “switch-on” PDT nanoplatform, whichemploys a well-designed hairpin structure mucl protein (MUC1) aptamer(Apt) as specific linker to conjugate gold nanorod and Chlorin e6 (Ce6) (GNR/Apt-Ce6) is prepared, and “switch on” via conformational changes of aptamerinduced fluorescence resonance energy transfer missing between GNR andCe6 for selective tumor therapy. In the absence of tumor cells, MUC1 Aptkeeps a hairpin structure, leading to Ce6 closely adhered to the surface ofGNR, PDT is in an “off” state even under the irradiations. On the contrary, inthe presence of tumor cells with overexpressed MUC1, Apt specifically recognizes and binds to MUC1, resulting in conformational changes of Apt fromregular hairpin to extended chain structure. Thus with an enlarged distancebetween Ce6 and GNR, PDT is switched-on. GNR/Apt-Ce6 shows excellentPDT efficacy in tumor-bearing mice (55.1% vs 1.3%, tumor apoptosis rate ofGNR/Apt-Ce6 vs GNR/random sequence-Ce6) due to its high tumor-targetingand “switch-on” properties. The strategy of tumor antigen activated PDT isexpected to provide a new perspective for clinical application

【全文链接】https://doi.org/10.1002/adhm.201900791