Investigation On DNA Biomaterials-based Nanocarrier Deliver Doxorubicin Into Cancer Cells

Drug therapy has been one of the most effective methods to treat cancer, anddrug delivery system is the carrier between cancer and drug, the drug deliverysystems can be optimized to achieve a better therapeutic effect.The DNA-based drugnano carrier has been one of the hottest research areas of biological materials.Specialproperties of nanomaterials enable us to delivery drug effectively in a way thatnormal drug delivery systems cann’t achieve currently.The anti-tumor anthracyclinedoxorubicin can be intercalate DNA duplexes, and they can form stable compounds.This study modified double-stranded DNA with cationic polymers RLT, CTAB andPEI, in order to evaluate and choose a best drug delivery system, so the drug nanocarrier can enhance the therapeutic effecticness.Purpose:Using different cationic polymers to construct modified double-stranded DNA,we evaluated effectiveness of in vitro characterization and anti-tumor effect of thecharacteristics of tumor cells, and chose the best drug delivery material and method.Methods:In this study, the first step is to preparation of DOX/DNA-RLT,DOX/DNA-CTAB and DOX/DNA-PEI nanocomplexs and then the particle size andzate potential and drug intercalation efficiency of the nanocomplexs weredetermined.In vitro durg release behaviors of DOX/DNA-RLT, DOX/DNA-CTABand DOX/DNA-PEI,cytotoxicity,intracelluar uptake and elimination of doxorubicinalso were investigated.Finally,we analyzed cell apoptosis analysis,cell cycle andreactive oxygen species(ROS).Results:We successfully constructed nano drug delivery by using DOX/DNA-RLT,DOX/DNA-CTAB and DOX/DNA-PEI and found the best suitable media isDOX/DNA-RLT.Its particle size and zeta potential of DOX/DNA-RLT are is421nm and8.15mVrespectively, The drug intercalation efficiency is79.56±0.09%and in vitro release drug is more slowly.Investigation of the cytology,DOX/DNA-RLT has a higher tumorcell inhibition.When1hour uptake in MCF-7cells,DOX is26.5±1.14%,DOX/DNAis27.1±0.38%,DOX/DNA-RLT is73.7±0.88%.In the48h,DOX of apoptosis is3.50±1.61%, necrosis is9.76±0.12%; DOX/DNA of apoptosis rate is19.99±0.11%,necrosis is13.43±0.23%; DOX/DNA-RLT of apoptosis rate is26.42±2.97%,necrosis is15.3±3.11%. DOX in G2/M is66.08±1.21%,DOX/DNA inG2/M is67.13±3.02%,DOX/DNA-RLT in G2/M is75.13±2.18%.DOX ratio ofROS when the6h is1.33±0.15,DOX/DNA is1.90±0.10,DOX/DNA-RLT is2.5±0.10;the24h is1.15±0.05, DOX/DNA is2.83±0.15,DOX/DNA-RLT is3.8±0.10.The above data are statistical significance for all comparisons.(P<0.05).Conclusions:DOX/DNA-RLT is drug nano carrier, constructed based on DNA biomaterial.This compound can encapusulate drug and embedded into nano-carrier.Nanobiological material can be encapsulated in nano-carrier drugs. It is stable,significantly improves the efficiency loading of drug and prolongs drug release time.It can not only enable the drug to last longer in tumor cells, but also prevent drug lostin the transportation process. By study of cytotoxicity, cellular uptake, apoptosis, cellcycle and ROS generation, we found it was a better material to target to tumor cells.And it increases anti-tumor effect, reduces the toxic side effects of the drug itself, andother characteristics. DOX/DNA-RLT is expected to become an effective drug nanocarrier in the future.