Tumor Targeting of Functionalized Quantum Dot-Liposome Hybrids by Intravenous Administration
Tumor Targeting of Functionalized Quantum Dot-Liposome Hybrids by Intravenous Administration
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DOI：
10.1021/mp800187d
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发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Kostarelos, Kostas
中科院分区：
文献类型：
--
作者：
All-Jamal, Wafa' T.;Al-Jamal, Khuloud T.;Kostarelos, Kostas
探索了在荷瘤小鼠实体瘤组织中靶向功能化量子块-脂质体（f-QD-L）杂化囊泡的策略。将官能化聚乙二醇（PEG）脂质包被的QD（f-QD）包封到100 nm阳离子（DOPC：Chol：DOTAP）、空间稳定的流体相（DOPC：Chol：DSPE-PEG（2000））和空间稳定的凝胶相（DSPC：Chol：DSPE-PEG（2000））脂质体囊泡的水性核心中。在携带B16 F10黑色素瘤肿瘤的C57 BL 6小鼠中静脉内施用后的不同时间点进行血液中f-QD-L的双重追踪。胆固醇[-1-C-14]油酸酯脂质探测囊泡膜后进行液体闪烁计数，同时使用电感耦合等离子体质谱法（ICP-MS）通过元素（Cd 2+）分析独立测定OD。在静脉内施用阳离子混合囊泡后观察到快速血液清除，而在两性离子囊泡表面掺入PEG在全身施用后显著延长其血液循环半衰期。“刚性”PEG化f-QD-L（DSPC：Chol：DSPE-PEG（2000））杂化囊泡导致OD峰值（约5%注射剂量/克组织）的快速肿瘤蓄积，相比之下，长循环f-QD在较长时间点蓄积在肿瘤组织中。更有趣的是，这种混合囊泡肿瘤保留持续至少24小时。对于几乎所有类型的系统，获得了肝脏和脾脏的优先镉吸收。总的来说，f-QD-L杂化囊泡由于其在肿瘤内的快速积累和长期保留而为肿瘤成像应用提供了巨大的潜力。此外，f-QD-L通过在单个囊泡的不同隔室中并入药物分子和QD两者，为开发组合治疗和成像（治疗诊断）模式提供了许多机会。
A strategy to target functionalized quantum clot-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized polyethylene glycol (PEG)lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 nm cationic (DOPC:Chol: DOTAP); sterically stabilized, fluid-phase (DOPC:Chol:DSPE-PEG(2000)); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG(2000)) liposome vesicles. Double tracking of f-QD-L in blood was performed at different time points after intravenous administration in B16F10 melanoma tumor-bearing C57BL6 mice. Cholesteryl [-1-C-14] oleate lipids probed the vesicle membrane were followed by liquid scintillation counting while OD were determined independently by elemental (Cd2+) analysis using inductively coupled plasma mass spectrometry (ICP-MS). Rapid blood clearance was observed following intravenous administration of the cationic hybrid vesicles, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. The "rigid" PEGylated f-QD-L (DSPC:Chol:DSPE-PEG(2000)) hybrid vesicles led to rapid tumor accumulation of peak values (approximately 5% of injected dose per gram tissue) of OD compared to long-circulating f-QD that accumulated in the tumor tissue at longer time points. More interestingly, this hybrid vesicle tumor retention persisted for at least 24 h. For almost all types of systems, a preferential cadmium uptake by liver and spleen was obtained. Overall, f-QD-L hybrid vesicles offer great potential for tumor imaging applications due to their rapid accumulation and prolonged retention within the tumor. Furthermore, f-QD-L offer many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.