Unsymmetric vesicles with a different design on each side for near-infrared fluorescence imaging of tumor tissues

Unsymmetric vesicles with a different design on each side for near-infrared fluorescence imaging of tumor tissues
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DOI:
10.1039/c4ra15635h
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发表时间:
2015-01
期刊:
影响因子:
3.9
通讯作者:
Akihiro Uesaka;I. Hara;T. Imai;J. Sugiyama;S. Kimura
Akihiro Uesaka;I. Hara;T. Imai;J. Sugiyama;S. Kimura
中科院分区:
化学3区
文献类型:
--
作者:
Akihiro Uesaka;I. Hara;T. Imai;J. Sugiyama;S. Kimura

文献摘要

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在立体复合物形成、偶极-偶极相互作用和空间位阻效应的控制下,由疏水B和B′嵌段中具有不同螺旋义的A3 B型和AB′型肽制备了具有不对称膜的球形囊泡组装体.将[(Sar)26]3-B-(L-Leu-Aib)6(A3 BL)、(Sar)27-B-(L-Leu-Aib)6(ABL)、(Sar)28-B-(D-Leu-Aib)6(ABD)、硫辛酸封端的ABL(lipoABL)和硫辛酸封端的ABD(lipoABD)混合,同时保持右手螺旋和左手螺旋总量的等摩尔比。当A3 BL超过混合物的所有右手螺旋的60%以上时,形成不对称囊泡,如通过TEM观察到的囊泡表面上的金纳米颗粒的选择性吸附所示。不对称囊泡也使用ICGABL和ICGABD与近红外荧光团,吲哚菁绿色(ICG),在ABL和ABD的末端制备。不对称囊泡的形成验证了荧光猝灭与In离子的溶液中加入。当将这些囊泡注射到荷瘤小鼠中时,囊泡通过EPR效应有效地积聚到肿瘤组织中。内表面含有ICG的不对称囊泡诱导的IgM产生少于外表面含有ICG的囊泡。因此,通过隐藏囊泡中的成像荧光团,可以获得血流中更多的隐形囊泡。
Spherical vesicular assemblies with unsymmetric membranes are prepared from A3B-type and AB′-type peptides with different helix senses in the hydrophobic B and B′ blocks under the control of three associated factors: stereo-complex formation, dipole–dipole interactions, and steric effects. [(Sar)26]3-b-(L-Leu-Aib)6 (A3BL), (Sar)27-b-(L-Leu-Aib)6 (ABL), (Sar)28-b-(D-Leu-Aib)6 (ABD), lipoic-acid terminated ABL (lipoABL), and lipoic-acid terminated ABD (lipoABD) are mixed while keeping equimolar ratios of the total amounts of the right- and the left-handed helices. When A3BL exceeds more than 60% of all the right-handed helices of the mixture, the unsymmetric vesicles are formed, as indicated by the selective adsorption of gold nanoparticles on the vesicle surface observed by TEM. The unsymmetric vesicles are also prepared using ICGABL and ICGABD with a near-infrared fluorophore, indocyanine green (ICG), at the terminals of ABL and ABD. The unsymmetric vesicle formation is verified by fluorescence quenching with the addition of In ions to the solution. When these vesicles are injected into tumor-bearing mice, the vesicles are effectively accumulated into tumor tissues via the EPR effect. The unsymmetric vesicle containing ICG at the inward surface induces less IgM production than that with ICG at the outward surface. More stealth vesicles in the blood stream are therefore obtainable by concealing the imaging fluorophores in the vesicle.