Toxicity Assessment Of Repeated Intravenous Injections Of RGD Peptide Conjugated Quantum Dots In Mice

Objective:To explore the virulence of NIR QDs-RGD when intravenously inject into mice singly and repeatedly at the dose required for successfully achieving tumor imaging in vivo.Methods:A NIR QDs-RGD probe was made by connecting NIR QDs to the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously administered to BALB/C mice one time or two times (200 pmol equivalent of QD800 for each injection), phosphate-buffered saline solution was as control. Fourteen days after injection, toxicity tests were carried out, including complete blood count (red blood cell, white blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (albumin, albumin/globulin, total protein, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of kidney, liver, spleen, and lung weight to body were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione and malondialdehyde. The organs were also examined histopathologically.Results:The concentration of prepared QD800-RGD was calculated to be 1.2 μM.Using the transmission electron microscope, The probe was found well dispersed into single particles. The integrin avβ3 was strongly expressed on HNSCC tumor angiogenic vessel endothelial cells. QD800-RGD can specifically bind to integrin avβ3 expressed in HNSCC tumor angiogenic vessel endothelial cells.Conclusion:Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our experient lays a good foundation for more biomedical applications of NIR QDs-RGD.