School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, P. R. China.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan Province, 450001, P. R. China.
Adv Healthc Mater. 2019 Oct;8(20):e1900791. doi: 10.1002/adhm.201900791. Epub 2019 Sep 18.
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.
光动力疗法（PDT）是一种非侵入性的强大肿瘤治疗工具。然而，光毒性严重限制了 PDT 的临床应用，并且很少有报道称激活的 PDT 能特异性响应肿瘤细胞抗原。在此，我们设计了一种肿瘤细胞特异性“开启”PDT 纳米平台，它采用精心设计的发夹结构 mucl 蛋白（MUC1）适体（Apt）作为特异性连接物，将金纳米棒和 Chlorin e6（Ce6）（GNR/Apt-Ce6）连接起来，并通过适体诱导的构象变化“开启”，实现金纳米棒和 Chlorin e6 之间荧光共振能量转移的缺失，从而实现选择性肿瘤治疗。在不存在肿瘤细胞的情况下，MUC1 Apt 保持发夹结构，导致 Ce6 紧密附着在 GNR 表面，即使在照射下，PDT 也处于“关闭”状态。相反，在过表达 MUC1 的肿瘤细胞存在的情况下，Apt 特异性识别并结合 MUC1，导致 Apt 从规则发夹结构到扩展链结构的构象变化。因此，随着 Ce6 和 GNR 之间距离的增大，PDT 被“开启”。由于其高肿瘤靶向性和“开启”特性，GNR/Apt-Ce6 在荷瘤小鼠中显示出优异的 PDT 疗效（55.1%对 1.3%，GNR/Apt-Ce6 对 GNR/随机序列-Ce6 的肿瘤凋亡率）。肿瘤抗原激活 PDT 的策略有望为临床应用提供新的视角。
