Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (*p< 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.
在全球范围内,宫颈癌是女性第四大常见癌症,其发病率和死亡率在资源匮乏地区尤为突出。本研究致力于开发一种液体免疫原性基准标记洗脱材料,其成分包含可生物降解聚合物、纳米颗粒及免疫佐剂。该材料旨在为晚期宫颈癌患者提供类似临床液体基准标记的放疗影像引导功能,同时增强治疗效果。研究采用C57BL6小鼠建立双侧皮下肿瘤模型,其中一侧肿瘤使用含抗CD40免疫佐剂的液体免疫原性基准标记洗脱材料进行治疗,并联合或不联合6 Gy剂量放疗。同时通过人体标本评估了该材料的计算机断层扫描与磁共振成像显影能力。此外,在健康C57BL6雌鼠中开展了药效动力学研究以评估材料安全性。结果显示,该材料能随时间推移同时提供CT与MR成像对比。放疗联合液体免疫原性基准标记洗脱材料治疗组持续观察到肿瘤生长抑制及生存期显著延长,凸显了该策略的潜力。与未治疗组相比,使用含或不含抗CD40佐剂的该材料对健康小鼠仅产生轻微毒性。这些结果表明,该策略有望通过进一步开发和临床转化,提升晚期宫颈癌患者的生存率与生活质量。