Ding Fei, Gao Xihui, Huang Xiangang, Ge Huan, Xie Miao, Qian Jiwen, Song Jie, Li Yuehua, Zhu Xinyuan, Zhang Chuan
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Shanghai, 200032, China.
Biomaterials. 2020 Jul;245:119976. doi: 10.1016/j.biomaterials.2020.119976. Epub 2020 Mar 16.
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)通常需要将肿瘤病灶的温度维持在50°C以上,这可能会引发局部炎症和肿瘤转移。为避免这些副作用,在PTT治疗期间,在相对低温(42-45°C)下实现有效的抗肿瘤疗效至关重要。在此,我们设计了一种聚多巴胺(PDA)包覆的核酸纳米凝胶作为用于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siRNAs作为交联剂,通过核酸杂交引导接枝了DNA的聚己内酯(DNA-g-PCL)组装成纳米尺寸的水凝胶颗粒。此后,将获得的包埋有siRNA的纳米凝胶进一步用一层薄薄的聚多巴胺包覆,这不仅保护纳米凝胶免受酶降解,还赋予纳米凝胶在近红外(NIR)光照射下出色的光热转换能力。经过表面聚乙二醇化后,这种三重屏蔽的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。