Effects Of Doxorubicin Nano Delivery Systems On Mouse Breast Cancer Cells

Background: Breast cancer,in developing countries in the female tumor mortality is very high,so the treatment of breast cancer is very urgent.At present,traditional chemotherapeutic drμgs have some problems such as toxicity and drμg resistance.Nano-delivery system may be the breakthroμgh to solve these problems.But does nano-drμg have the same effect as free drμg? The issue has not yet been fully articulated.To solve this problem,this study changed the dosage form of the first-line drμg of breast cancer such as adriamycin(DOX).Polyglycerol-functionalized nano-diamond(ND-PG)and nano-diamond-carbon point complex(ND-PG-CD)carried DOX respectively.We prepared two kinds of nano-delivery complexes of DOX,ND-PG-DOX and ND-PG-CD-DOX.Subsequently,we studied the effects of two kinds of nano-dox on 4T1 cells of breast cancer in mice using 4T1 cells as the model and free DOX as the control.Objective: The effects of two doxorubicin nanoparticles and free doxorubicin on the toxicity and drμg resistance of 4T1 cells were compared.Methods:(1)The ND is pg-modified and the surface is aminated.Carbon points are synthesized by microwave method.They are connected by amide bond,and then CD and DOX are connected by π-π bond to synthesize ND-PG-CD-DOX.(2)To investigate the effects of ND-PG-CD-DOX,ND-PG-DOX,DOX on cell uptake,subcellular distribution,cytotoxicity,and drμg resistance mediated by p-glycoprotein were detected.Results:(1)Physical and chemical characterization analysis showed that ND-PG-CD-DOX and ND-PG-DOX were successfully prepared.(2)Drμg release rate in vitro showed that the drμg release rate of ND-PG-CD-DOX was faster than that of ND-PG-DOX under the same conditions.DOX is mainly distributed in the nucleus,while two nano forms of DOX are mainly distributed in the cytoplasm.(3)Cytotoxicity: DOX>ND-PG-CD-DOX>ND-PG-DOX.(4)DOX significantly up-regulated the expression of P-gp.But the effects of the two nano-drμgs were weak.P-gp significantly affected the cytotoxicity of DOX,but not significantly on the two nano-drμgs.Conclusion: DOX is linked differently with the three drμgs,resulting in different release rates,subcellular distribution and cellular effects.In terms of cell effect,free DOX had the strongest inhibitory effect to breast cancer cells,but had a strong induction effect on P-gp.However,the inhibition of nano-form DOX on tumor cells was weaker than that of free DOX.And the induction of P-gp was also significantly weaker than that of DOX.