Nanovehicles as a novel target strategy for hyperthermic intraperitoneal chemotherapy: a multidisciplinary study of peritoneal carcinomatosis

Abstract

In general, detection of peritoneal carcinomatosis (PC) occurs at the late stage when there is no treatment option. In the present study, we designed novel drug delivery systems that are functionalized with anti-CD133 antibodies. The C1, C2 and C3 complexes with cisplatin were introduced into nanotubes, either physically or chemically. The complexes were reacted with anti-CD133 antibody to form the labeled product of A0-o-CX-chem-CD133. Cytotoxicity screening of all the complexes was performed on CHO cells. Data showed that both C2 and C3 Pt-complexes are more cytotoxic than C1. Flow-cytometry analysis showed that nanotubes conjugated to CD133 antibody have the ability to target cells expressing the CD133 antigen which is responsible for the emergence of resistance to chemotherapy and disease recurrence. The shortest survival rate was observed in the control mice group (K3) where no hyperthermic intraperitoneal chemotherapy procedures were used. On the other hand, the longest median survival rate was observed in the group treated with A0-o-C1-chem-CD133. In summary, we designed a novel drug delivery system based on carbon nanotubes loaded with Pt-prodrugs and functionalized with anti-CD133 antibodies. Our data demonstrates the effectiveness of the new drug delivery system and provides a novel therapeutic modality in the treatment of melanoma.

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

“…In a recent study by Nowacki et al [94], HIPEC was performed in mice using a nano-sized drug delivery system based on carbon nanotubes (CNTs) [95]. Briefly, CNTs loaded with cisplatin were functionalized with the anti-CD133 antibody to reduce the resistance to chemotherapy, emerging from the CD133 antigen.…”

“…Briefly, CNTs loaded with cisplatin were functionalized with the anti-CD133 antibody to reduce the resistance to chemotherapy, emerging from the CD133 antigen. When the CNTs functionalized with anti-CD133 were applied IP via the HIPEC procedure in the abdomen of mice bearing peritoneal B16 melanoma tumors, the best general survival (12.6 days) observed was for the functionalized CNTs, and the shortest general survival (8 days) was for the mice in which the HIPEC procedure was not carried-out [94]. Likewise, De Smet et al [96] investigated the suitability of PTX nanosuspension stabilized by Pluronic F127® for HIPEC treatment in rats bearing SKOV-3 ovarian cancer.…”

Multifunctional platinum‐based nanoparticles for biomedical applications

“…With increasing awareness of the potential advantages, many delivery systems have been developed for improved IP administration of platinum drugs on peritoneal malignancies. For example, a Pt‐prodrugs loaded carbon nanotube functionalized with anti‐CD133 was prepared for peritoneal carcinomatosis treatment by IP administration in mice . The functionalization of anti‐CD133 prolonged the median survival rate in the IP treatment of Pt‐prodrug loaded carbon nanotubes.…”

The scientific report from the first pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures performed in the eastern part of Central Europe

“…Peritoneal carcinomatosis (PC) is a devastating diagnosis characterized by a rapidly progressing metastatic process derived from different types of primary neoplasms involving the peritoneal cavity, which is commonly classified and treated as stage IV. 1 – 3 The most common primary tumours that metastasize to the peritoneal cavity include ovarian and digestive-tract cancers. 4 , 5 For many years, gastroenterologists and surgical oncologists considered PC to be a considerable challenge.…”

“…As PC was considered to be the terminal stage of the disease, patients were referred for palliative treatment with only a modest portfolio of therapeutic options. 2 , 6 , 7 This situation had arisen because patients with PC and a gastrointestinal primary tumour have a poor prognosis with a relatively short median survival time compared with other types of metastasis. 8 Notably, the median time of survival for patients receiving only supportive care and standard palliative treatment has been estimated as 1–3 months for patients suffering from PC of gastric cancer origin, 16–17 months for patients with PC of colorectal cancer origin receiving only systemic chemotherapy and 14–24 months for patients with PC of ovarian origin.…”