Silencing of Intestinal Glycoprotein CD98 by Orally Targeted Nanoparticles Enhances Chemosensitization of Colon Cancer.

Abstract

Colon cancer is among the most widely occurring cancer types, leading to considerably high mortality rate. The current chemotherapy achieves only limited success, and more effective therapeutic strategies are urgently needed. Human colonic biopsy specimens indicate increased expression of CD98 in patients with colon cancer, suggesting that CD98 might be a potential therapeutic target and/or a receptor for targeted drug delivery in colon cancer treatment. Herein, we coloaded CD98 siRNA (siCD98) and camptothecin (CPT) into CD98 Fab'-functionalized nanoparticles (NPs). The resultant Fab'-siCD98/CPT-NPs showed good monodispersity with an average diameter of approximately 270 nm and a ζ-potential of around -24 mV. These NPs mediated efficient drug delivery to the target cancer cells and tumor tissues, producing much better anticancer and antimigration effects compared to other relevant NPs. Mouse models with orthotopic colon tumors were treated with NP-embedded hydrogel, which revealed that Fab'-siCD98/CPT-NPs exhibited a therapeutic efficacy significantly better than that of single drug-loaded NPs or nonfunctionalized siCD98/CPT-NPs. This study indicates that the Fab'-siCD98/CPT-NP/hydrogel system is able to realize specific release of NPs in the colonic lumen and enable drugs (siCD98 and CPT) to be internalized into target cells, demonstrating a notable potential for clinical applications in colon-cancer-targeted combination therapy.

• Authors: Bo Xiao, Emilie Viennois, Qiubing Chen, Lixin Wang, Moon Kwon Han, Yuchen Zhang, Zhan Zhang, Yuejun Kang, Ying Wan, Didier Merlin
• Journal: ACS nano (ACS Nano) Vol. 12 Issue 6 Pg. 5253-5265 (06 26 2018) ISSN: 1936-086X [Electronic] United States
• PMID: 29860836 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Fusion Regulatory Protein-1
• RNA, Small Interfering
• Camptothecin

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Camptothecin (pharmacology)
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Disease Models, Animal
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Female
• Fusion Regulatory Protein-1 (biosynthesis, deficiency, genetics)
• Humans
• Intestines (drug effects, pathology)
• Mice
• Mice, Inbred C57BL
• Nanoparticles (administration & dosage)
• Neoplasms, Experimental (drug therapy, metabolism, pathology)
• RNA, Small Interfering (administration & dosage)