Using a Membrane-Penetrating-Peptide to Anchor Ligands in the Liposome Membrane Facilitates Targeted Drug Delivery.,Bioconjugate Chemistry

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Using a Membrane-Penetrating-Peptide to Anchor Ligands in the Liposome Membrane Facilitates Targeted Drug Delivery.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-12-27 , DOI: 10.1021/acs.bioconjchem.9b00798
Xiaobo Fan ₁ , Hongbo Xu ₁ , Junlong Song ₂ , Yongcan Jin ₂ , Michael Wink ₃ , Guoqiu Wu ₄

Affiliation

Antimicrobial peptides (AMPs) are typical cell penetrating peptides (CPPs) that intercalate into biomembranes and exhibit broad activities. We designed a triple fusion protein consisting of an AMP, Ib-AMP4 at the N-terminus, a fluorescent GFP probe in the center, and the tumor-targeting peptide P1c at the other terminus. After purification from E. coli, the interaction between the Ib-AMP4-GFP-P1c fusion protein (IGP) and the lipid membrane was characterized. Experiments using isothermal titration calorimetry (ITC) and quartz crystal microbalance with dissipation (QCM-D) demonstrated that IGP proteins spontaneously bound the lipid bilayer with a maximal molar ratio of 1:52 (protein:lipid). Furthermore, transmission electron microscopy (TEM) confirmed that the IGP protein was present in the liposome membrane. After decoration with IGP proteins, the DOPC:DOPG liposomes were applied to cancer cells. Microscopy and flow cytometry reveal that the decorated liposomes selectively bound integrin αvβ3-positive A549 cells. In addition, compared with the common chemical conjugation method, the reported method seemed to be superior in certain aspects, such as simple sample preparation and cost-effectiveness. Next, the IGP protein was applied to decorate red blood cell (RBC) liposomes for targeted delivery in both in vitro and in vivo applications. The IGP-decorated RBC liposomes preferentially targeted integrin αvβ3 expressing A549 cancer cells. The in vivo imaging showed that IGP-decorated RBC liposomes were concentrated in tumor tissue and were primarily metabolized by the liver and kidney.

中文翻译：

使用膜穿透肽锚定脂质体膜中的配体有助于靶向药物递送。

抗菌肽（AMP）是典型的细胞穿透肽（CPP），可插入生物膜并具有广泛的活性。我们设计了一个三重融合蛋白，该蛋白由AMP，N端的Ib-AMP4，中心的荧光GFP探针和另一端的肿瘤靶向肽P1c组成。从大肠杆菌中纯化后，表征了Ib-AMP4-GFP-P1c融合蛋白（IGP）与脂质膜之间的相互作用。使用等温滴定热法（ITC）和带耗散的石英晶体微量天平（QCM-D）进行的实验表明，IGP蛋白自发结合脂质双层，最大摩尔比为1:52（蛋白质：脂质）。此外，透射电子显微镜（TEM）证实了IGP蛋白存在于脂质体膜中。用IGP蛋白修饰后，将DOPC：DOPG脂质体应用于癌细胞。显微镜和流式细胞仪显示，修饰的脂质体选择性结合整联蛋白αvβ3阳性的A549细胞。另外，与普通的化学结合方法相比，所报道的方法在某些方面似乎更优越，例如简单的样品制备和成本效益。接下来，将IGP蛋白用于修饰红细胞（RBC）脂质体，以在体外和体内应用中靶向递送。具有IGP装饰的RBC脂质体优先靶向表达整联蛋白αvβ3的A549癌细胞。体内成像显示，装饰有IGP的RBC脂质体集中在肿瘤组织中，并主要通过肝脏和肾脏代谢。显微镜和流式细胞仪显示，修饰的脂质体选择性结合整联蛋白αvβ3阳性的A549细胞。另外，与普通的化学结合方法相比，所报道的方法在某些方面似乎更优越，例如简单的样品制备和成本效益。接下来，将IGP蛋白用于修饰红细胞（RBC）脂质体，以在体外和体内应用中靶向递送。具有IGP装饰的RBC脂质体优先靶向表达整联蛋白αvβ3的A549癌细胞。体内成像显示，装饰有IGP的RBC脂质体集中在肿瘤组织中，并主要通过肝脏和肾脏代谢。显微镜和流式细胞仪显示，修饰的脂质体选择性结合整联蛋白αvβ3阳性的A549细胞。另外，与普通的化学结合方法相比，所报道的方法在某些方面似乎更优越，例如简单的样品制备和成本效益。接下来，将IGP蛋白应用于修饰红细胞（RBC）脂质体，以在体外和体内应用中靶向递送。具有IGP装饰的RBC脂质体优先靶向表达整联蛋白αvβ3的A549癌细胞。体内成像显示，装饰有IGP的RBC脂质体集中在肿瘤组织中，并主要通过肝脏和肾脏代谢。所报道的方法在某些方面似乎是优越的，例如简单的样品制备和成本效益。接下来，将IGP蛋白应用于修饰红细胞（RBC）脂质体，以在体外和体内应用中靶向递送。具有IGP装饰的RBC脂质体优先靶向表达整联蛋白αvβ3的A549癌细胞。体内成像显示，装饰有IGP的RBC脂质体集中在肿瘤组织中，并主要通过肝脏和肾脏代谢。所报道的方法在某些方面似乎是优越的，例如简单的样品制备和成本效益。接下来，将IGP蛋白应用于修饰红细胞（RBC）脂质体，以在体外和体内应用中靶向递送。具有IGP装饰的RBC脂质体优先靶向表达整联蛋白αvβ3的A549癌细胞。体内成像显示，装饰有IGP的RBC脂质体集中在肿瘤组织中，并主要通过肝脏和肾脏代谢。

更新日期：2019-12-29

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