Mostafa Akbarzadeh Khiavi
1,2 
, Azam Safary
2,3 , Jaleh Barar
2,4 , Hamed Farzi-Khajeh
5, Abolfazl Barzegari
2, Rahimeh Mousavi
2, Mohammad Hossein Somi
1* , Yadollah Omidi
2,4* 1 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, 51656-65811, Iran
3 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5 Organosilicon Research Laboratory, Faculty of Chemistry, University of Tabriz, Tabriz, Iran
Abstract
Introduction: Currently, drug-induced reactive oxygen species (ROS) mediating apoptosis pathway have extensively been investigated in designing effective strategies for colorectal cancer (CRC) chemotherapy. Bovine pancreatic ribonuclease A (RNase A) represents a new class of cytotoxic and non-mutagenic enzymes, and has gained more attention as a potential anticancer modality; however, the cytosolic ribonuclease inhibitors (RIs) restrict the clinical application of this enzyme. Nowadays, nanotechnology-based diagnostic and therapeutic systems have provided potential solutions for cancer treatments.
Methods: In this study, the gold nanoparticles (AuNPs) were synthesized, stabilized by polyethylene glycol (PEG), functionalized, and covalently conjugated with RNase A. The physicochemical properties of engineered nanobiomedicine (AuNPs-PEG-RNase A) were characterized by scanning electron microscope (SEM), dynamic light scattering (DLS), and UV-vis spectrum. Then, its biological impacts including cell viability, apoptosis, and ROS production were evaluated in the SW-480 cells.
Results: The engineered nanobiomedicine, AuNPs-PEG-RNase A, was found to effectively induce apoptosis in SW-480 cells and result in a significant reduction in cancer cell viability. Besides, the maximum production of ROS was obtained after the treatment of cells with an IC50 dose of AuNPs-PEG-RNase A.
Conclusion: Based on the efficient ROS-responsiveness and the anticancer activity of RNase A of the engineered nanomedicine, this nanoscaled biologics may be considered as a potential candidate for the treatment of CRC.