PDF(Pubmed)
Abstract：
Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first-line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti-tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.
摘要：
患有结直肠癌（CRC）和弥漫性腹膜转移（PM）的患者不适合进行手术干预。因此，姑息治疗仍然是临床实践中的标准护理。全身化疗未能导致药物在病变部位积聚，而腹膜内化疗（IPC）受到高清除率和相关并发症的限制。鉴于预后不良，已经设计了定制的OxP/R848@PLEL水凝胶递送系统,以提高弥漫性PM晚期CRC的临床获益。这个系统的特点是简单，安全,和效率。具体来说,PLEL水凝胶具有优异的可注射性和热敏感性，能够在腹腔内形成药物库，使其成为IPC的最佳载体。奥沙利铂（OxP），晚期CRC的一线药物，具有细胞毒性并通过诱导免疫原性细胞死亡增强肿瘤的免疫原性。此外，OxP和瑞喹莫特（R848）协同增强树突状细胞的成熟，促进细胞毒性T淋巴细胞的扩增，并诱导中枢记忆T细胞的形成。此外，R848将巨噬细胞驯化为抗肿瘤表型。OxP/R848@PLEL可有效根除腹膜转移，完全抑制腹水的产生，并显著延长小鼠寿命。因此，它为无手术指征的CRC患者治疗弥漫性PM提供了一种有前景的方法.
