Leslie L. Dan Faculty of Pharmacy, University of Toronto, and Department of Medical Biophysics, University Health Network, Princess Margaret Hospital, 144 College Street, Toronto, Ontario, Canada, M5S 3M2.
ACS Nano. 2011 Mar 22;5(3):1958-66. doi: 10.1021/nn103024b. Epub 2011 Feb 21.
Despite broad applications of quantum dots (QDs) in vitro, severe toxicity and dominant liver uptake have limited their clinical application. QDs that excite and emit in the ultraviolet and visible regions have limited in vivo applicability due to significant optical interference exerted by biological fluids and tissues. Hence we devised a new biocompatible hybrid fluorophore composed of near-infrared-emitting PbSe quantum dots encapsulated in solid fatty ester nanoparticles (QD-FEN) for in vivo imaging. The quantum yield and tissue penetration depth of the QD-FEN were characterized, and their biological fate was examined in a breast tumor-bearing animal model. It was found for the first time that chemical modification of the headgroup of QD-encapsulating organic fatty acids was a must as these groups quenched the photoluminescence of PbSe nanocrystals. The use of fatty esters enhanced aqueous quantum yields of PbSe QDs up to ∼45%, which was 50% higher than that of water-soluble PbSe nanocrystals in an aqueous medium. As a result, a greater than previously reported tissue penetration depth of fluorescence was recorded at 710 nm/840 nm excitation/emission wavelengths. The QD-FEN had much lower short-term cytotoxicity compared to nonencapsulated water-soluble QDs. More importantly, reduced liver uptake, increased tumor retention, lack of toxic response, and nearly complete clearance of QD-FEN from the tested animals was demonstrated. With a combination of near-infrared spectral properties, enhanced optical properties,and significantly improved biosafety profile, this novel hybrid nanoparticulate fluorophore system demonstrably provides real-time, deep-tissue fluorescent imaging of live animals, laying a foundation for further development toward clinical application.
尽管量子点 (QD) 在体外得到了广泛的应用，但严重的毒性和主要的肝脏摄取限制了它们的临床应用。在紫外和可见光区域激发和发射的 QD 由于生物流体和组织施加的显著光学干扰，其体内适用性有限。因此，我们设计了一种由近红外发射的 PbSe 量子点包封在固体脂肪酯纳米颗粒中的新型生物相容性杂化荧光团 (QD-FEN)，用于体内成像。我们对 QD-FEN 的量子产率和组织穿透深度进行了表征，并在乳腺癌荷瘤动物模型中研究了它们的生物学命运。我们首次发现，必须对包封 QD 的有机脂肪酸的头基进行化学修饰，因为这些基团会猝灭 PbSe 纳米晶体的光致发光。酯的使用将 PbSe QD 的水相量子产率提高到约 45%，比在水相中的水溶性 PbSe 纳米晶体高 50%。结果，在 710nm/840nm 激发/发射波长下记录到荧光的组织穿透深度大于以前的报道。与未封装的水溶性 QD 相比，QD-FEN 的短期细胞毒性要低得多。更重要的是，与未封装的水溶性 QD 相比，QD-FEN 显示出较低的肝摄取、增加的肿瘤保留、缺乏毒性反应以及从测试动物中几乎完全清除 QD-FEN。这种新型杂化纳米颗粒荧光团系统具有近红外光谱特性、增强的光学特性和显著提高的生物安全性，可实现活体动物的实时、深层组织荧光成像，为进一步开发临床应用奠定了基础。
