Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
ACS Nano. 2017 Mar 28;11(3):3038-3051. doi: 10.1021/acsnano.7b00016. Epub 2017 Feb 20.
Quantum dots (QDs), semiconductor nanocrystals, are fluorescent nanoparticles of growing interest as an imaging tool of a diseased tissue. However, a major concern is their biocompatibility, cytotoxicity, and fluorescence instability in biological milieu, impeding their use in biomedical applications, in general, and for inflammation imaging, in particular. In addition, for an efficient fluorescent signal at the desired tissue, and avoiding systemic biodistribution and possible toxicity, targeting is desired. We hypothesized that phagocytic cells of the innate immunity system (mainly circulating monocytes) can be exploited as transporters of specially designed liposomes containing QDs to the inflamed tissue. We developed a liposomal delivery system of QDs (LipQDs) characterized with high encapsulation yield, enhanced optical properties including far-red emission wavelength and fluorescent stability, high quantum yield, and protracted fluorescent decay lifetime. Treatment with LipQDs, rather than free QDs, exhibited high accumulation and retention following intravenous administration in carotid-injured rats (an inflammatory model). QD-monocyte colocalization was detected in the inflamed arterial segment only following treatment with LipQDs. No cytotoxicity was observed following LipQD treatment in cell cultures, and changes in liver enzymes and gross histopathological changes were not detected in mice and rats, respectively. Our results suggest that the LipQD formulation could be a promising strategy for imaging inflammation.
量子点(QD)是半导体纳米晶体,作为病变组织的成像工具,其越来越受到关注。然而,人们主要关注的是其在生物环境中的生物相容性、细胞毒性和荧光稳定性,这阻碍了它们在一般生物医学应用中的使用,特别是在炎症成像中的使用。此外,为了在所需组织中获得有效的荧光信号,并避免全身分布和可能的毒性,需要进行靶向。我们假设先天免疫系统的吞噬细胞(主要是循环单核细胞)可以被利用为含有 QD 的专门设计的脂质体的转运体,将其递送到炎症组织。我们开发了一种具有高包封率的 QD 脂质体(LipQDs)的递药系统,其光学特性得到了增强,包括远红发射波长和荧光稳定性、高量子产率和延长的荧光衰减寿命。与游离 QD 相比,在颈动脉损伤大鼠(炎症模型)中静脉给药后,LipQDs 的蓄积和保留明显增加。只有在用 LipQDs 处理后,才能在炎症动脉段中检测到 QD-单核细胞的共定位。在细胞培养中,用 LipQD 处理后没有观察到细胞毒性,在小鼠和大鼠中分别没有检测到肝酶变化和大体组织病理学变化。我们的结果表明,LipQD 制剂可能是一种有前途的炎症成像策略。