Hollow mesoporous ruthenium nanoparticles conjugated bispecific antibody for targeted anti-colorectal cancer response of combination therapy
Hollow mesoporous ruthenium nanoparticles conjugated bispecific antibody for targeted anti-colorectal cancer response of combination therapy
复制标题
中空介孔钌纳米粒子缀合双特异性抗体用于靶向抗结直肠癌联合治疗反应
作者：
Xu Meng;Wen Yayu;Liu Yanan;Tan Xianjie;Chen Xu;Zhu Xufeng;Wei Chunfang;Chen Lanmei;Wang Zhong;Liu Jie
基于肿瘤靶向纳米颗粒的联合治疗已成为最有前途的抗癌策略之一。此外，双特异性抗体被设计为促进自然杀伤细胞（NK）和肿瘤细胞之间相互作用的连接体，同时触发NK细胞介导的靶细胞裂解。在这里，我们采用了一种新颖的设计，使用聚乙二醇化的中空介孔钌纳米颗粒作为载体，装载荧光抗肿瘤复合物([Ru（bpy)2(tip)]2+， RBT）和双特异性抗体（SS-Fc）的偶联物。通过精确靶向结直肠癌细胞中过表达的癌胚抗原，HMRu@RBT-SS-Fc显著提高了体外选择性渗透。功能化的纳米复合物能有效吸附NK细胞，具有优异的近红外敏感细胞毒性。系统的体内研究清楚地表明，光热联合免疫治疗在异位结直肠癌模型中具有较高的肿瘤靶向性和抗癌活性。这种纳米系统为未来的图像引导药物传递和高效的癌症治疗建立了一个新的平台。
Combined treatment based on tumor-targeted nanoparticles has become one of the most promising anticancer strategies. Moreover, bispecific antibodies have been designed as linkers to promote the interaction between natural killer (NK) cells and tumor cells, while triggering NK cell-mediated target cell lysis. Here, we adopted a novel design that uses PEGylated hollow mesoporous ruthenium nanoparticles as a carrier to load the fluorescent anti-tumor complex ([Ru(bpy)2(tip)]2+, RBT) and a conjugate with bispecific antibodies (SS-Fc). By accurately targeting carcinoembryonic antigen overexpressed in colorectal cancer cells, HMRu@RBT-SS-Fc significantly improved selective penetration in vitro. The functionalized nanocomplex effectively engaged NK cells and possessed excellent near infrared-sensitive cytotoxicity. Systematic in vivo studies clearly demonstrated the high tumor targeting and anticancer activity in heterotopic colorectal tumor model via combined photothermal and immune therapy. This nanosystem establishes a new platform for future image-guided drug delivery and highly efficient cancer therapy.