Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

Many ribonucleases (RNases) are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from , triggers apoptotic response in cancer cells expressing oncogene which is mutated in a large percentage of prevalent and deadly mal...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in pharmacology 2017-09, Vol.8, p.631
Main Authors: Khodzhaeva, Vera, Makeeva, Anna, Ulyanova, Vera, Zelenikhin, Pavel, Evtugyn, Vladimir, Hardt, Martin, Rozhina, Elvira, Lvov, Yuri, Fakhrullin, Rawil, Ilinskaya, Olga
Format: Article
Language:English
Subjects:
Bacillus pumilus
binase
colon adenocarcinoma
halloysite
nanotubes
Pharmacology
RNase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Many ribonucleases (RNases) are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from , triggers apoptotic response in cancer cells expressing oncogene which is mutated in a large percentage of prevalent and deadly malignancies including colorectal cancer. The specific antitumor effect of binase toward RAS-transformed cells is due to its direct binding of RAS protein and inhibition of downstream signaling. However, the delivery of proteins to the intestine is complicated by their degradation in the digestive tract and subsequent loss of therapeutic activity. Therefore, the search of new systems for effective delivery of therapeutic proteins is an actual task. This study is aimed to the investigation of antitumor effect of binase immobilized on natural halloysite nanotubes (HNTs). Here, we have developed the method of binase immobilization on HNTs and optimized the conditions for the enzyme loading and release (i); we have found the non-toxic concentration of pure HNTs which allows to distinguish HNTs- and binase-induced cytotoxic effects (ii); using dark-field and fluorescent microscopy we have proved the absorption of binase-loaded HNTs on the cell surface (iii) and demonstrated that binase-halloysite nanoformulations possessed twice enhanced cytotoxicity toward tumor colon cells as compared to the cytotoxicity of binase itself (iv). The enhanced antitumor activity of biocompatible binase-HNTs complex confirms the advisability of its future development for clinical practice.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2017.00631