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Photodynamic therapy (PDT) is a noninvasive powerful tool for tumor treatment. However, phototoxicity seriously limits the clinical application of PDT, and activated PDT specifically response to tumor cell antigen is rarely reported. Herein, a tumor cell specific "switch-on" PDT nanoplatform, which employs 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 aptamer-induced fluorescence resonance energy transfer missing between GNR and Ce6 for selective tumor therapy. In the absence of tumor cells, MUC1 Apt keeps a hairpin structure, leading to Ce6 closely adhered to the surface of GNR, PDT is in an "off" state even under the irradiations. On the contrary, in the presence of tumor cells with overexpressed MUC1, Apt specifically recognizes and binds to MUC1, resulting in conformational changes of Apt from regular hairpin to extended chain structure. Thus with an enlarged distance between Ce6 and GNR, PDT is switched-on. GNR/Apt-Ce6 shows excellent PDT efficacy in tumor-bearing mice (55.1% vs 1.3%, tumor apoptosis rate of GNR/Apt-Ce6 vs GNR/random sequence-Ce6) due to its high tumor-targeting and "switch-on" properties. The strategy of tumor antigen activated PDT is expected to provide a new perspective for clinical application.
PMID: 31532896 [PubMed - as supplied by publisher]