Ye Hao, Wang Kaiyuan, Lu Qi, Zhao Jian, Wang Menglin, Kan Qiming, Zhang Haotian, Wang Yongjun, He Zhonggui, Sun Jin
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
Biomaterials. 2020 Jun;242:119932. doi: 10.1016/j.biomaterials.2020.119932. Epub 2020 Mar 4.
Breast cancer contributes to high mortality rates as a result of metastasis. Tumor-derived exosomes facilitate the development of the premetastatic environment, interacting and inhibiting the normal function of immune cells, thereby forming an immunosuppressive microenvironment for tumor metastasis. Herein, the platelet and neutrophil hybrid cell membrane (PNM) was embellished on a gold nanocage (AuNC) surface called nanosponges and nanokillers (NSKs). NSKs can simultaneously capture and clear the circulating tumor cells (CTCs) and tumor-derived exosomes via high-affinity membrane adhesion receptors, effectively cutting off the connection between exosomes and immune cells. Bionic NSK is loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergic chemo-photothermal therapy. NSKs show greater cellular uptake, deeper tumor penetration, and higher cytotoxicity to tumor cells in comparison to non-coated AuNCs or single-coated AuNCs in vitro. In vivo, the multipurpose NSKs could not only completely ablate the primary tumor but also inhibit breast cancer metastasis with high efficiency in xenograft and orthotopic breast tumor-bearing models. Thus, NSKs could be a promising nanomedicine for the future clinical intervention of breast cancer metastasis.
乳腺癌由于转移导致高死亡率。肿瘤衍生的外泌体促进了转移前环境的形成，与免疫细胞相互作用并抑制其正常功能，从而形成了有利于肿瘤转移的免疫抑制微环境。在此，血小板和中性粒细胞杂交细胞膜（PNM）被修饰在金纳米笼（AuNC）表面，称为纳米海绵和纳米杀手（NSK）。NSK可以通过高亲和力膜粘附受体同时捕获和清除循环肿瘤细胞（CTC）和肿瘤衍生的外泌体，有效切断外泌体与免疫细胞之间的联系。仿生NSK负载了阿霉素（DOX）和吲哚菁绿（ICG）用于协同化学光热疗法。与未包被的AuNC或单包被的AuNC相比，NSK在体外对肿瘤细胞表现出更高的细胞摄取、更深的肿瘤渗透和更高的细胞毒性。在体内，多功能NSK不仅可以完全消融原发性肿瘤，还能在异种移植和原位荷瘤乳腺癌模型中高效抑制乳腺癌转移。因此，NSK有望成为未来乳腺癌转移临床干预的纳米药物。
