Xu Yurui, Zhou Anwei, Chen Weiwei, Yan Yuxin, Chen Kerong, Zhou Xinyuan, Tian Zihan, Zhang Xiaomin, Wu Heming, Fu Zhen, Ning Xinghai
National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China.
National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, School of Physics, Nanjing University, Nanjing, 210093, China.
Adv Mater. 2023 Dec;35(49):e2304172. doi: 10.1002/adma.202304172. Epub 2023 Oct 27.
Although tumor models have revolutionized perspectives on cancer aetiology and treatment, current cell culture methods remain challenges in constructing organotypic tumor with in vivo-like complexity, especially native characteristics, leading to unpredictable results for in vivo responses. Herein, the bioorthogonal nanoengineering strategy (BONE) for building photothermal dynamic tumor spheroids is developed. In this process, biosynthetic machinery incorporated bioorthogonal azide reporters into cell surface glycoconjugates, followed by reacting with multivalent click ligand (ClickRod) that is composed of hyaluronic acid-functionalized gold nanorod carrying dibenzocyclooctyne moieties, resulting in rapid construction of tumor spheroids. BONE can effectively assemble different cancer cells and immune cells together to construct heterogenous tumor spheroids is identified. Particularly, ClickRod exhibited favorable photothermal activity, which precisely promoted cell activity and shaped physiological microenvironment, leading to formation of dynamic features of original tumor, such as heterogeneous cell population and pluripotency, different maturation levels, and physiological gradients. Importantly, BONE not only offered a promising platform for investigating tumorigenesis and therapeutic response, but also improved establishment of subcutaneous xenograft model under mild photo-stimulation, thereby significantly advancing cancer research. Therefore, the first bioorthogonal nanoengineering strategy for developing dynamic tumor models, which have the potential for bridging gaps between in vitro and in vivo research is presented.
尽管肿瘤模型彻底改变了人们对癌症病因和治疗的看法，但目前的细胞培养方法在构建具有类似体内复杂性，尤其是天然特征的器官型肿瘤方面仍然面临挑战，导致体内反应结果不可预测。在此，开发了用于构建光热动态肿瘤球体的生物正交纳米工程策略（BONE）。在此过程中，生物合成机制将生物正交叠氮化物报告基团整合到细胞表面糖缀合物中，随后与由携带二苯并环辛炔部分的透明质酸功能化金纳米棒组成的多价点击配体（ClickRod）反应，从而快速构建肿瘤球体。已确定BONE可以有效地将不同的癌细胞和免疫细胞组装在一起，以构建异质性肿瘤球体。特别地，ClickRod表现出良好的光热活性，精确地促进了细胞活性并塑造了生理微环境，导致形成原始肿瘤的动态特征，如异质细胞群体和多能性、不同的成熟水平以及生理梯度。重要的是，BONE不仅为研究肿瘤发生和治疗反应提供了一个有前景的平台，还在温和的光刺激下改善了皮下异种移植模型的建立，从而显著推动了癌症研究。因此，提出了首个用于开发动态肿瘤模型的生物正交纳米工程策略，该策略有潜力弥合体外和体内研究之间的差距。
