Department of Biomedical Engineering and Department of Mechanical Engineering , Johns Hopkins University , Maryland 21218 , United States.
School of Life Science and Technology , University of Electronic Science and Technology of China , Chengdu 610054 , China.
ACS Nano. 2019 Mar 26;13(3):2849-2857. doi: 10.1021/acsnano.8b03788. Epub 2019 Mar 4.
Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.
虽然抗 PD-1 免疫疗法被广泛用于治疗黑色素瘤，但它的疗效仍有待提高。在这项工作中，我们提出了一种将免疫疗法和饥饿疗法相结合的治疗方法，以达到更好的抗肿瘤疗效。我们设计了 CMSN-GOx 方法，其中介孔硅纳米粒子 (MSN) 负载葡萄糖氧化酶 (GOx)，然后包裹细胞膜以实现饥饿疗法。通过对 MSN 的仿生表面进行功能化，我们可以合成能够逃避宿主免疫系统和同源靶标的纳米粒子。这些特性使纳米粒子具有更好的癌症靶向能力和在肿瘤组织中的富集能力。我们合成的 CMSN-GOx 复合物可以消融肿瘤并诱导树突状细胞成熟，从而刺激抗肿瘤免疫反应。我们对这些纳米粒子进行了体内分析，结果表明，我们的联合治疗 CMSN-GOx 加 PD-1 比单独使用 CMSN-GOx 或 PD-1 的治疗具有更好的抗肿瘤治疗效果。此外，我们还使用正电子发射断层扫描成像来测量肿瘤组织中葡萄糖代谢的水平，以研究体内癌症治疗的效果。
