Abstract:

Objective To study the toxicity of near-infrared quantum dots (NIR QDs) linked to peptide containing the arginine-glycine-aspartic acid (RGD) sequence (NIR QDs-RGD) in the mice,and to clarify the biological safety of NIR QDs-RGD as a novel tumor treatment method. Methods The probe was prepared firstly by linking NIR QDs to the RGD peptide.Twenty-four BALB/C mice were randomly divided into four groups.In QD800-RGD one injection group,the mice were injected via tail vein with 100 μL QD800-RGD (equivalent to 200 pmol of QD800) on the first day;in PBS one injection group,the mice were injected similarly with 100 μL PBS;in QD800-RGD two injection group,the mice were repeatedly injected via tail vein with 100 μL QD800-RGD (equivalent to 200 pmol of QD800) on the first and seventh days;in PBS two injection group,the mice were repeatedly injected similarly with 100 μL PBS on the first and seventh days.Fourteen days after injection,toxicity tests were performed,including complete blood cells(white blood cells,red blood cells,hemoglobin,platelets,lymphocytes,and neutrophils) count and serum biochemical analysis (total protein,albumin,albumin/globulin,aspartate aminotransferase,alanine aminotransferase,and blood urea nitrogen).The coefficients of liver,spleen,kidney,and lung weight to body weight were calculated,and the activities of superoxide dismutase(SOD),glutathione(GSH),and malondialdehyde(MDA) contents in liver,spleen,kidney and lung tissues of the mice were detected.The histopathological examination was performed. Results Compared with PBS injcetion groups,the organ coefficients of the mice in QD800-RGD one injection group were decreased slightly,and the organ coefficients of the mice in QD800-RGD two injection group were increased,but the differences between four groups were not statistically significant (P>0.05).Compared with PBS injcetion groups,the number of leukocytes,erythrocytes,lymphocytes and the levels of hemoglobin and platelets were increased,and the number of neutrophils had no significant change;the number of red blood cells,lymphocytes and hemoglobin level in QD800-RGD two injection group were increased;the number of white blood cells and the level of platelets were decreased,and the number of neutrophils had no significant changes;but the differences were not statistically significant between four groups (P>0.05).Compared with PBS injection group,the total protein,albumin,albumin globulin ratio,and blood urea nitrogen in QD800-RGD one injection group were reduced;the aspartate aminotransferase and alanine aminotransferase were increased;the total protein and albumin were increased,the albumin globulin ratio,blood urea nitrogen,aspartate aminotransferase and alanine aminotransferase in QD800-GRD two injection group were decreased;but the differences were not statistically significant between four groups (P>0.05). Compared with PBS injection group,the activities of SOD,GSH and the MDA contents in liver,spleen,kidney and lung tissues in QD800-RGD one injection group and QD800-RGD two injection group were slightly increased;but the differences were not statistically significant between four groups (P>0.05). Compared with PBS injection group,the morphology of liver,spleen,kidney and lung tissues in QD800-RGD one injection group and QD800-RGD two injection group were normal,the cells agganged orderly, and no necrosis was seen. Conclusion At the dose needed to produce in vivo tumor imaging,there is no significant toxicity of NIR QD800-RGD in the mice after repeatedly intravenous injection.

Key words: near-infrared quantum dots, RGD peptide, toxicity