Xia Chengwan, Pan Jiongru, Wang Jianquan, Pu Yumei, Zhang Qian, Hu Shiqi, Hu Qingang, Wang Yuxin
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
School of Medical Imaging, Bengbu Medical College, Bengbu, 233030, China.
Nanoscale. 2020 Oct 14;12(38):19833-19843. doi: 10.1039/d0nr04682e. Epub 2020 Sep 24.
Cancer-associated fibroblasts (CAFs) play a critical role in the onset and progression of malignancies, such as oral squamous cell carcinoma (OSCC), making CAFs a promising druggable target. In this study, gold nanoparticles (GNPs) exhibited unprecedented size dependent anti-CAF potential, wherein the smallest GNPs outperformed their larger counterparts. Specifically, a subset of proteins and cytokines that is responsible for the invasive outgrowth of OSCC cells was found to decrease post exposure of OSCC patient-derived CAFs to GNPs. Moreover, the administration of GNPs (3 nm in diameter) could effectively abrogate the growth of OSCC tumors in vivo, offering a novel means to manage OSCC in the clinic. Besides targeting cancer cells, our results collectively verify the feasibility of blocking dominant cells in the microenvironment to eradicate tumors, shedding light on the future design of nanomedicines.
癌症相关成纤维细胞（CAFs）在恶性肿瘤（如口腔鳞状细胞癌，OSCC）的发生和发展中起着关键作用，这使得CAFs成为一个有前景的可药物作用靶点。在本研究中，金纳米颗粒（GNPs）展现出前所未有的尺寸依赖性抗CAF潜力，其中最小的GNPs比其较大的同类表现更优。具体而言，发现一组负责OSCC细胞侵袭性生长的蛋白质和细胞因子在OSCC患者来源的CAFs暴露于GNPs后减少。此外，施用直径为3纳米的GNPs可有效消除体内OSCC肿瘤的生长，为临床治疗OSCC提供了一种新方法。除了靶向癌细胞外，我们的结果共同验证了通过阻断微环境中的主导细胞来根除肿瘤的可行性，为纳米药物的未来设计提供了思路。
