Nanovehicles as a novel target strategy for hyperthermic intraperitoneal chemotherapy: a multidisciplinary study of peritoneal carcinomatosis
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Maciej Nowacki1, Marek Wisniewski2,3, Karolina Werengowska-Ciecwierz2, Katarzyna Roszek4, Joanna Czarnecka4, I. Łakomska5, Tomasz Kloskowski1, Dominik Tyloch1, Robert Debski6, Katarzyna Pietkun1,7, Marta Pokrywczynska1, Dariusz Grzanka7, Rafał Czajkowski7, Gerard Drewa8, A. Jundziłł1, Joseph K. Agyin9, Samy L. Habib10,11, Artur P. Terzyk2 and Tomasz Drewa1,12
1 Chair of Regenerative Medicine, Tissue Engineering Department, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz Nicolaus Copernicus University, Torun, Poland
2 Physicochemistry of Carbon Materials Research Group, Faculty of Chemistry, Nicolaus Copernicus University in Torun, Poland
3 Invest-Tech, Research and Development Center, Torun, Poland
4 Department of Biochemistry, Faculty of Biology and Environment Protection, Nicolaus Copernicus University in Torun, Poland
5 Faculty of Chemistry, Nicolaus Copernicus University in Torun, Poland
6 Department of Pediatric Hematology and Oncology, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, Poland
7 Chair of Dermatology Department, Faculty of Medicine, Nicolaus Copernicus University, Toruń, Sexually Transmitted Diseases and Immunodermatology, Bydgoszcz, Poland
8 Department of Medical Biology, University of Bydgoszcz, Poland
9 Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX, USA
10 Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX, USA
11 Department of Geriatric, South Texas Veterans Health System, The University of Texas Health Science Center, San Antonio, TX, USA
12 Urology Department, Nicolaus Copernicus Hospital in Torun, Torun, Poland
Maciej Nowacki, email:
Samy L. Habib, email:
Keywords: carcinomatosis, palliative, hyperthermic intraperitoneal chemotherapy, intraperitoneal perfusion and nanovehicles
Received: April 03, 2015 Accepted: May 13, 2015 Published: May 27, 2015
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.
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