Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

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

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.

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

Synchronous chemotherapy and radiotherapy,termed chemoradiation therapy,is now an important standard regime for synergistic cancer treatment.For such treatment,nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy.Herein,we designed a Schottky-type theranostic heterostructure,Bi_(2)S_(3)-Au,with deep level defects(DLDs)in Bi_(2)S_(3) as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation.Methotrexate(MTX)was conjugated onto the Bi_(2)S_(3)-Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior.The designed hybrid system also contained curcumin(CUR),which cannot only serve as a nutritional supplement for chemotherapy,but also can play an important role in the radioprotection of normal cells.Impressively,this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation,completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.