Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer.

Abstract

Colorectal cancer is the third most frequently diagnosed cancer malignancy and the second leading cause of cancer-related deaths worldwide. Therefore, it is of utmost importance to provide new therapeutic options that can improve survival. Sphingomyelin nanosystems (SNs) are a promising type of nanocarriers with potential for association of different types of drugs and, thus, for the development of combination treatments. In this work we propose the chemical modification of uroguanylin, a natural ligand for the Guanylyl Cyclase (GCC) receptor, expressed in metastatic colorectal cancer tumors, to favour its anchoring to SNs (UroGm-SNs). The anti-cancer drug etoposide (Etp) was additionally encapsulated for the development of a combination strategy (UroGm-Etp-SNs). Results from in vitro studies showed that UroGm-Etp-SNs can interact with colorectal cancer cells that express the GCC receptor and mediate an antiproliferative response, which is more remarkable for the drugs in combination. The potential of UroGm-Etp-SNs to treat metastatic colorectal cancer cells was complemented with an in vivo experiment in a xenograft mice model.

• Authors: Belén L Bouzo, Saínza Lores, Raneem Jatal, Sandra Alijas, María José Alonso, Inmaculada Conejos-Sánchez, María de la Fuente
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 17213 (08 26 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34446776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antineoplastic Agents, Phytogenic
• Natriuretic Peptides
• Sphingomyelins
• uroguanylin
• Etoposide
• Receptors, Guanylate Cyclase-Coupled

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Drug Delivery Systems (methods)
• Etoposide (administration & dosage, chemistry, pharmacology)
• Female
• Humans
• Mice, Inbred Strains
• Mice, Nude
• Microscopy, Electron, Scanning
• Nanoparticles (chemistry, ultrastructure)
• Natriuretic Peptides (chemistry, metabolism)
• Neoplasm Metastasis
• Particle Size
• Receptors, Guanylate Cyclase-Coupled (metabolism)
• Sphingomyelins (chemistry)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays (methods)