Lipid-quanturn dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo
Lipid-quanturn dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo
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DOI：
10.1021/nn700176a
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发表时间：
2008-03-01
期刊：
影响因子：
17.1
通讯作者：
Kostarelos, Kostas
中科院分区：
文献类型：
--
作者：
Al-Jamal, Wafa T.;Al-Jamal, Khuloud T.;Kostarelos, Kostas
我们报告的建设脂质量子点（L-OD）双层囊泡的最小的（2 nm的核心大小）市售的CdSe/ZnS量子点内的两性离子二油酰磷脂酰胆碱和阳离子1，2-二油酰-3-三甲基铵-丙烷脂质双层，自组装成小的单层囊泡。脂质双层的酰基环境中的QD的掺入导致显着增强的光学稳定性，在存储和暴露于紫外线照射相比，QD单独在甲苯中。此外，使用低温电子显微镜的L-QD混合双层囊泡的结构表征表明，QD的掺入发生在生物膜内的疏水性自缔合。L-QD囊泡在人上皮肺细胞（A549）中结合并内化，并且共聚焦激光扫描显微镜研究表明L-QD能够在细胞内运输。此外，将阳离子L-QD囊泡在体内瘤内注射，导致在人宫颈癌（C33 a）异种移植物内的保留增强。本文提出的混合L-QD双层囊泡被认为构成了一种新的递送系统，其提供了将组合治疗和诊断模式在体外和体内运输至癌细胞的潜力。
We report the construction of lipid-quantum dot (L-OD) bilayer vesicles by incorporation of the smallest (2 nm core size) commercially available CdSe/ZnS QD within zwitterionic dioleoylphosphatidylcholine and cationic 1,2-dioleoyl-3-trimethylammonium-propane lipid bilayers, self-assembling into small unilamellar vesicles. The incorporation of QD in the acyl environment of the lipid bilayer led to significant enhancement of their optical stability during storage and exposure to UV irradiation compared to that of QD alone in toluene. Moreover, structural characterization of L-QD hybrid bilayer vesicles using cryogenic electron microscopy revealed that the incorporation of QD takes place by hydrophobic self-association within the biomembranes. The L-QD vesicles bound and internalized in human epithelial lung cells (A549), and confocal laser scanning microscopy studies indicated that the L-QD were able to intracellularly traffick inside the cells. Moreover, cationic L-QD vesicles were injected in vivo intratumorally, leading to enhanced retention within human cervical carcinoma (C33a) xenografts. The hybrid L-QD bilayer vesicles presented here are thought to constitute a novel delivery system that offers the potential for transport of combinatory therapeutic and diagnostic modalities to cancer cells in vitro and in vivo.