Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells  

作　　者：ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI 

机构地区：[1]Department of Medical Biotechnology,School of Medicine,Zanjan University of Medical Sciences,Zanjan,Iran [2]Nanotechnology Research Center,Ahvaz Jundishapur University of Medical Sciences,Ahvaz,Iran [3]Zanjan Pharmaceutical Biotechnology Research Center,Zanjan University of Medical Sciences,Zanjan,Iran [4]Department of Pharmaceutical Biotechnology,School of Pharmacy,Zanjan University of Medical Sciences,Zanjan,Iran [5]Molecular Medicine Department,Biotechnology Research Center,Pasteur Institute of Iran,Pasteur Avenue,Tehran,Iran [6]Department of Radiology Technology,School of Allied Medical Sciences,Zanjan University of Medical Sciences,Zanjan,Iran

出　　处：《Oncology Research》2024年第1期101-125,共25页肿瘤学研究（英文）

基　　金：Zanjan University of Medical Sciences supported the present study(Grant Number:A-12-1244-18).

摘　　要：In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关 键 词：CHEMORADIOTHERAPY Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer 

分 类 号：R737.25[医药卫生—肿瘤]