A peptide-lipid nanoparticle assembly platform with integrated functions for targeted cell delivery.
A peptide-lipid nanoparticle assembly platform with integrated functions for targeted cell delivery.
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DOI：
10.1039/c5tb02783g
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Qiao Wang;Xiaochuan Ma;Junli Jia;H. Fei
中科院分区：
文献类型：
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作者：
Qiao Wang;Xiaochuan Ma;Junli Jia;H. Fei
脂质体由于其生物相容性、低毒性和控释特性而被广泛用作药物载体，然而在控制其粒径、表面特性和靶向功能方面存在挑战。在这项工作中，我们报告了一种肽-脂质纳米颗粒平台，可以在集成组装过程中实现纳米颗粒形成、表面功能化和疏水性药物负载。使用具有通过中心环连接的二价两亲性α-螺旋的设计肽（ALA肽）来包封脂质纳米颗粒（LNP）。二价设计提供了更高的肽螺旋度和脂质包装效率，并允许包封的疏水分子在长期储存下具有更高的稳定性。中心环结构显示出足够的表面暴露，如通过五组氨酸安装的LNP和Ni-NTA琼脂糖之间的相互作用所证明的。RGD插入和细胞毒性铱络合物封装的LNP显示出对整合素高表达癌细胞的优先进入和选择性细胞毒性，同时显示出对非癌细胞的毒性降低。进一步的研究表明，一个受约束的环状构象的RGD是需要充分发挥靶向能力，这表明一个完整的结构暴露在LNP表面。总之，我们展示了一种简单而有效的基于肽的LNP表面修饰方法，其具有用于疏水药物的各种靶向递送的潜力。
Liposomes are extensively used as drug carriers because of their biocompatibility, low toxicity, and controlled release properties, however challenges exist in the control of their particle size, surface properties and targeting functionality. In this work, we report a peptide-lipid nanoparticle platform that can achieve nanoparticle formation, surface functionalization and hydrophobic drug loading in an integrated assembly process. A designer peptide that harbors bivalent amphipathic α-helices linked by a central loop (ALA peptide) was used to encapsulate lipid nanoparticles (LNPs). The bivalency design affords higher peptide helicity and lipid-packaging efficiency, and allows encapsulated hydrophobic molecules for more stability under long-term storage. The central loop structure displays sufficient surface exposure as demonstrated by the interaction between penta-histidine installed LNPs and Ni-NTA agarose. RGD-inserted and cytotoxic iridium complex-encapsulated LNPs showed preferential entry and selective cytotoxicity to integrin high expression cancer cells, while showing reduced toxicity to non-cancer cells. Further study indicates that a constrained cyclic conformation of RGD is required to fully exert targeting capability, suggesting an intact structural exposure on the LNP surface. In summary, we demonstrate a simple yet effective method of peptide-based LNP surface modification with potential for various targeted deliveries of hydrophobic drugs.