RGD肽段连接的近红外量子点对小鼠的毒性作用

发布时间：2018-05-02 07:14

本文选题：近红外量子点 + RGD肽段　；参考：《吉林大学学报(医学版)》2015年04期

【摘要】：目的:探讨近红外量子点(NIR QDs)与含有精氨酸-甘氨酸-天冬氨酸序列(RGD)肽段连接的NIR QDs-RGD探针对小鼠的毒性作用,阐明NIR QDs-RGD作为一种新型肿瘤治疗手段的生物安全性。方法:用NIR-QDS与RGD肽段连接,制备探针;将24只BALB/C小鼠随机分为4组,单次注射组在第1天通过尾静脉注射100μL的QD800-RGD(含200pmol的QD800);单次注射对照组在第1天通过尾静脉注射100μL的PBS;重复注射组分别在第1天和第7天通过尾静脉各注射100μL的QD800-RGD(含200pmol的QD800);重复注射对照组分别在第1天和第7天通过尾静脉各注射100μL的PBS。注射14d后行毒性检测,包括小鼠全血细胞(白细胞、红细胞、血红蛋白、血小板、淋巴细胞和中性粒细胞)计数和血清生化分析(总蛋白、白蛋白、白球比、天门冬氨酸氨基转换酶、丙氨酸氨基转换酶和血尿素氮),计算小鼠肝、脾、肾和肺的脏器系数,检测肝、脾、肾和肺组织中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)活性和丙二醛(MDA)含量,并进行组织病理学检查。结果:与各自对照组比较,单次注射组小鼠脏器系数稍有降低,重复注射组小鼠脏器系数增高,但4组小鼠之间比较差异无统计学意义(P0.05)。全血细胞计数,与对照组比较,单次注射组小鼠白细胞、红细胞、血红蛋白、血小板、淋巴细胞数都有所增高,中性粒细胞数未见明显变化;重复注射组小鼠红细胞、血红蛋白、淋巴细胞增高,白细胞、血小板减少,中性粒细胞无明显变化;4组之间比较差异无统计学意义(P0.05)。血清生化指标检测,与对照组比较,单次注射组小鼠总蛋白、白蛋白、白球比、血尿素氮减少,天门冬氨酸氨基转换酶和丙氨酸氨基转换酶增加;重复注射组小鼠总蛋白、白蛋白增加,白球比、血尿素氮减少,天门冬氨酸氨基转换酶和丙氨酸氨基转换酶降低;4组之间比较差异无统计学意义(P0.05)。氧化和抗氧化指标的检测,与对照组比较,单次注射组和重复注射组小鼠肝、脾、肾和肺组织中SOD、GSH活性、MDA含量有少量增加,但4组之间比较差异无统计学意义(P0.05)。肝、脾、肾和肺组织病理学检查,与对照组比较,单次注射组和重复注射组小鼠肝、脾、肾和肺的细胞形态规则,分布排列有序,均无坏死。结论:NIR QD800-RGD在能达到对体内肿瘤成像所需的剂量下重复静脉注射在小鼠体内未导致明显的毒性作用。
[Abstract]:Aim: to investigate the toxicity of NIR QDs-RGD probe containing arginine-glycine-aspartate sequence peptide to mice, and to elucidate the biological safety of NIR QDs-RGD as a new tumor therapy. Methods: 24 BALB/C mice were randomly divided into 4 groups, which were connected with RGD peptide segment by NIR-QDS, and the probes were prepared. In the single injection group, 100 渭 L QD800-RGD100 渭 L QD800-RGD100 渭 L was injected through the caudal vein on the first day, the control group was injected 100 渭 L PBS100 渭 L through the tail vein on the 1st day, and the QD800-RGD100 渭 L QD800-RGD100 渭 L each on the 7th day in the repeated injection group. QD800 containing 200pmol and 100 渭 L PBSs were injected into the tail vein of the control group on day 1 and day 7, respectively. Toxicity tests were performed 14 days after injection, including whole blood cell counts (white blood cells, red blood cells, hemoglobin, platelets, lymphocytes and neutrophils) and serum biochemical analysis (total protein, albumin, globular ratio) in mice. Aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen were used to calculate the organ coefficients of liver, spleen, kidney and lung of mice, and to detect the activity of superoxide dismutase (SOD), glutathione (GSH) and the content of malondialdehyde (MDA) in liver, spleen, kidney and lung. Histopathological examination was performed. Results: compared with the control group, the viscera coefficient of the single injection group was slightly lower than that of the repeated injection group, but there was no significant difference among the four groups (P 0.05). Compared with the control group, the number of leukocytes, erythrocytes, hemoglobin, platelets and lymphocytes in the single injection group increased, but the neutrophil count did not change. Hemoglobin, lymphocyte, leukopenia, leukopenia, neutrophilic granulocyte had no significant difference among the four groups (P 0.05). Compared with the control group, the total protein, white ball ratio, blood urea nitrogen decreased, aspartate aminotransferase and alanine aminotransferase increased in the single injection group, and the total protein in the repeated injection group was higher than that in the control group. There was no significant difference among the four groups: albumin increased, white ball ratio, blood urea nitrogen decreased, aspartate aminotransferase and alanine aminotransferase decreased. There was no significant difference among the four groups (P 0.05). Compared with the control group, the content of MDA in liver, spleen, kidney and lung of single injection group and repeated injection group increased slightly, but there was no significant difference among the four groups (P 0.05). Compared with the control group, the liver, spleen, kidney and lung of single injection group and repeated injection group had regular cellular morphology, orderly distribution and no necrosis in liver, spleen, kidney and lung. Conclusion repeated intravenous injection of QD800-RGD at the dose required for tumor imaging in vivo did not lead to significant toxicity in mice.
【作者单位】：重庆医科大学附属第一医院口腔颌面外科;重庆医科大学现代教育技术中心;
【基金】：国家自然科学基金资助课题(81172205)
【分类号】：R965

【参考文献】