Enzymatic Regioselection for the Synthesis and Biodegradation of Porphysome Nanovesicles
Enzymatic Regioselection for the Synthesis and Biodegradation of Porphysome Nanovesicles
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DOI：
10.1002/anie.201108280
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Zheng, Gang
中科院分区：
文献类型：
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作者：
Lovell, Jonathan F.;Jin, Cheng S.;Zheng, Gang
我们最近报道了卟啉-磷脂偶联物可以自组装成由致密的卟啉双层组成的“卟啉体”纳米囊泡。[1]卟啉囊泡表现出结构驱动的纳米级光学性质，并具有用于多模态成像、药物递送和光热治疗的固有能力。以前的研究是基于由两种化学上相似的磷脂卟啉区域异构体的混合物形成的卟啉囊泡。然而，使用区域异构体的混合物对于体外和体内的稳健的纳米颗粒表征来说远非理想。一般来说，在合成，检测和区分磷脂区域异构体的困难，阻止检查他们在体内的命运，直到现在。据我们所知，本文报道的结果首次证明了任何固有光学活性纳米颗粒的体内酶促生物降解性，这一特征在考虑在人体临床试验中使用新纳米材料时可能很重要。化学改性磷脂已被证明可用于各种生物技术应用。[2-4]磷脂可以在其头基或侧链上的各个位置进行标记。[5]虽然使用磷脂酰乙醇胺的伯胺基团可以容易地实现头基修饰，但侧链修饰不那么直接，但适合于缀合更疏水的配体，同时保持两亲性磷脂特性。最近，已经开发了用胆固醇、视黄酸和卟啉侧链修饰的磷脂，其显示出用于药物递送、免疫学和生物光子应用的有用性质。[1，6 - 9]单侧链修饰磷脂的合成经常受到侧链酰基迁移的影响。所得的区域异构体（例如，图1a）具有相似的结构，这使得它们的分离不切实际，并且它们的检测具有挑战性或不可能使用HPLC、NMR光谱和质谱等技术。[10]区域选择性磷脂侧链修饰已经使用许多技术实现。改性磷脂的合成已在多步反应中使用改性甘油骨架进行，有时需要保护基团。[6，9，11]溶血素的酰化
We recently reported that porphyrin–phospholipid conjugates can self-assemble into “porphysome” nanovesicles composed of a dense porphyrin bilayer.[1] Porphysomes exhibit structurally driven nanoscale optical properties and have intrinsic capabilities for multimodal imaging, drug delivery, and photothermal therapy. Previous studies were based on porphysomes formed from a mixture of two chemically similar phospholipid–porphyrin regioisomers. However, use of a mixture of regioisomers is far from ideal for robust nanoparticle characterization in vitro and in vivo. In general, difficulties in synthesizing, detecting, and distinguishing phospholipid regioisomers have prevented examination of their in vivo fate until now. To our knowledge, the results reported herein are the first to demonstrate in vivo enzymatic biodegradability for any intrinsically optically active nanoparticle, a feature that might be important when considering the use of new nanomaterials in human clinical trials. Chemically modified phospholipids have proven useful for diverse biotechnology applications.[2–4] Phospholipids can be labeled at various positions on their head group or side chain.[5] While head-group modification can readily be achieved using the primary amine group of phosphatidylethanolamine, side-chain modification is less straightforward but is appropriate for conjugating more hydrophobic ligands while maintaining an amphipathic phospholipid character. Recently, phospholipids modified with cholesterol, retinoic acid, and porphyrin side chains have been developed that display useful properties for drug-delivery, immunological, and biophotonic applications.[1, 6–9] Synthesis of single sidechain-modified phospholipids is often affected by acyl migration of the side chains. The resulting regioisomers (eg, Figure 1a) have similar structures, which make their separation impractical and their detection challenging or impossible using techniques such as HPLC, NMR spectroscopy, and mass spectrometry.[10] Regioselective phospholipid side-chain modification has been achieved using a number of techniques. Synthesis of modified phospholipids has been performed in multistep reactions using a modified glycerol backbone, with protecting groups sometimes being required.[6, 9, 11] Acylation of lyso-