Photothermal therapy (PTT) normally requires to maintain the temperature of tumor lesions above 50 °C, which potentially induces local inflammation and tumor metastasis. To avoid these side effects, it is vital to achieve effective antitumor efficacy at relatively low temperature (42–45 °C) during the PTT treatment. Herein, we design a polydopamine (PDA)-coated nucleic acid nanogel as a therapeutic complex for siRNA-mediated low-temperature PTT. First, siRNAs that target the heat-shock-protein 70 (Hsp70) serve as crosslinkers to guide the DNA-grafted polycaprolactone (DNA-g-PCL) assemble into nanosized hydrogel particles through nucleic acid hybridization. Thereafter, the obtained siRNA-embedded nanogels are further coated with a thin layer of polydopamine, which not only protects the nanogels against enzymatic degradation but also endows the nanogels with excellent photothermal conversion capacity under near infrared (NIR) light irradiation. After surface PEGylation, this triple shield siRNA delivery complex shows the capability of effective ablating the tumor under relatively mild condition.

光热疗法（PTT）通常需要将肿瘤病变的温度维持在50°C以上，这有可能诱发局部炎症和肿瘤转移。为避免这些副作用，在PTT治疗期间在相对较低的温度（42–45°C）下获得有效的抗肿瘤功效至关重要。在本文中，我们设计了聚多巴胺（PDA）涂层的核酸纳米凝胶，作为siRNA介导的低温PTT的治疗复合物。首先，靶向热休克蛋白70（Hsp70）的siRNA作为交联剂，指导DNA接枝的聚己内酯（DNA- g-PCL）通过核酸杂交组装成纳米级水凝胶颗粒。此后，将获得的嵌入siRNA的纳米凝胶进一步涂上一层聚多巴胺薄层，这不仅可以保护纳米凝胶免于酶促降解，而且还使纳米凝胶在近红外（NIR）光照射下具有出色的光热转化能力。表面聚乙二醇化后，这种三重屏蔽siRNA递送复合物显示出在相对温和的条件下有效消融肿瘤的能力。