Official websites use. Share sensitive information only on official, secure websites. Corresponding Author: Kazuki N. Sugahara, sugahara sanfordburnham. Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy IPC is an area of intense interest given its efficacy in ovarian cancer.
However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice.
Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice.
These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis. Keywords: peritoneal carcinomatosis, intraperitoneal chemotherapy, tumor-penetrating peptide, integrin, neuropilin.
The metastases cause complications that are not easily palliated, such as bowel obstruction and ascites. Systemic chemotherapy is less active against peritoneal metastasis than visceral metastasis. Tumor cell aggregates that float in ascites or have just attached to the peritoneum lack vasculature, preventing blood-borne drugs from reaching the tumor cells 5 , 6.
