Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA; Department of Oncology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Biomaterials. 2022 Oct;289:121769. doi: 10.1016/j.biomaterials.2022.121769. Epub 2022 Sep 1.
Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24 h after intravascular injection of DCM-[PTX] at 5 mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2 Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6 Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.
低剂量无毒二硫键交联胶束（DCM）包载紫杉醇（PTX）被发现是一种高效的放射增敏剂，可用于口腔癌临床前模型。在血管内注射 5mg/kgPTX 的 DCM-[PTX] 后 24 小时，连续 3 天局部给予调强放疗。与常规 PTX 联合放疗相比，DCM-[PTX] NPs 联合常规放疗（2Gy）可使治疗效果提高 1.7 倍。有趣的是，我们发现放疗可以降低紧密连接并增加肿瘤部位 DCM-[PTX]的积累。立体定向体部放疗（SBRT）给予 6Gy 用于进一步研究协同抗肿瘤作用。收集肿瘤组织分析 SBRT 后时间间隔与纳米材料生物分布之间的关系。与常规剂量的联合 DCM-[PTX]相比，SBRT 联合 DCM-PTX 更能有效抑制肿瘤生长。
