Hoshino Akiyoshi, Hanada Sanshiro, Manabe Noriyoshi, Nakayama Toshinori, Yamamoto Kenji
International Clinical Research Center, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan.
IEEE Trans Nanobioscience. 2009 Mar;8(1):51-7. doi: 10.1109/TNB.2009.2016550. Epub 2009 Mar 16.
Fluorescent nanocrystal quantum dots (QDs) are widely used as novel tools in various biological fields including cellular biology, molecular biology, and even in basic and clinical medical fields, due to their far brighter photoemission and photostability. Although many amounts of biological studies, including in vivo experiments, were circumstantially investigated, there is no informative report that investigates whether the QDs affect the mammalian immune system. This study investigated the immune response and biological behavior of QDs in vitro and in vivo. The immune response to QDs by both lymphocytes and kinds of macrophages in vitro and in vivo was investigated. Co-culture of QDs with immune cells showed that apparently normal production of cytokines and chemokines in both mouse CD4+ lymphocytes and peritoneal F4/80+ macrophages (PM phi). In addition, the bionanocomplex of QDs with enhanced-green-fluorescent-protein (eGFP)-encoding nucleotides successfully induced the expression of eGFP protein by PM phi. However, direct injection of QD+nucleotides bionanocomplex aqueous solution into the peritoneal cavity of mice resulted in the inflammation with the infiltration of inflammatory cells into the peritoneal cavity. Furthermore, QD+nucleotides bionanocomplex (but not QD bionanocomplex without nucleotides), induced the production of both proinflammatory cytokines and chemokines by PM phi in vitro. These results indicated that QDs covered with nucleotides caused the peritoneal inflammation in vivo via activation of PM phi and probably nonimmune cells. Taken together, these data indicated that QDs affect the proliferation of immune cells, but not in immune response including cytokine production. We propose here that all nanotechnology researchers should confirm the biological responses of their nanoscale products, because the biological response against nanoscale products can be occurred by not only in immune cells but also other nonimmune cells.
荧光纳米晶体量子点（QDs）因其更明亮的光发射和光稳定性，被广泛用作细胞生物学、分子生物学等各种生物学领域，甚至基础和临床医学领域的新型工具。尽管已经对包括体内实验在内的大量生物学研究进行了间接调查，但尚无关于量子点是否影响哺乳动物免疫系统的详实报告。本研究调查了量子点在体外和体内的免疫反应及生物学行为。研究了淋巴细胞和多种巨噬细胞在体外和体内对量子点的免疫反应。量子点与免疫细胞的共培养表明，小鼠CD4 + 淋巴细胞和腹膜F4/80 + 巨噬细胞（PM phi）中细胞因子和趋化因子的产生明显正常。此外，量子点与编码增强型绿色荧光蛋白（eGFP）的核苷酸的生物纳米复合物成功诱导了PM phi表达eGFP蛋白。然而，将量子点+核苷酸生物纳米复合水溶液直接注射到小鼠腹腔中会导致炎症，炎症细胞浸润到腹腔中。此外，量子点+核苷酸生物纳米复合物（而非不含核苷酸的量子点生物纳米复合物）在体外诱导PM phi产生促炎细胞因子和趋化因子。这些结果表明，被核苷酸覆盖的量子点通过激活PM phi和可能的非免疫细胞在体内引起腹膜炎症。综上所述，这些数据表明量子点影响免疫细胞的增殖，但不影响包括细胞因子产生在内的免疫反应。我们在此提议，所有纳米技术研究人员都应确认其纳米级产品的生物学反应，因为对纳米级产品的生物学反应不仅可能发生在免疫细胞中，也可能发生在其他非免疫细胞中。
