Abstract：
As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPRILK) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.
摘要：
作为甲状腺乳头状癌（PTC）的传统治疗方法，手术切除病变组织常常给患者带来很多不便,肿瘤复发和转移难以避免。在这里，我们开发了一种基于聚吡咯(Ppy)-聚(乙烯亚胺)-siILK纳米复合物(PPRILK)的基因和光热联合治疗纳米系统,以同时实现PTC的微创消融和淋巴转移抑制.在这个系统中,明胶稳定的Ppy主要充当光热和光声（PA）响应的纳米材料，并有助于其在近红外区域表现良好的光敏性。此外，明胶稳定的Ppy具有电荷逆转功能，促进siILK基因在生理pH（7.35-7.45）时的紧密连接，并自动释放到酸性溶酶体（pH4.0-5.5）中；在此过程中产生的质子海绵效应进一步促进siILK从溶酶体逃逸到细胞质，并在抑制PTC增殖和淋巴转移中发挥作用。在荧光和PA双峰成像的指导下，可以清楚地观察到肿瘤区域的基因传递和Ppy位置。因此,肿瘤被光热疗法完全根除，siILK明显抑制复发和转移。
