The lipid composition affects Trastuzumab adsorption at monolayers at the air-water interface

被引:21
|
作者
Sakai, Andrei [1 ]
de Sousa Mesquista, Ana Paula [2 ]
Nader, Helena B. [1 ]
Lopes, Carla Cristina [1 ]
Nakanishi, Waka [3 ,4 ]
Ariga, Katsuhiko [3 ,5 ]
Caseli, Luciano [1 ]
机构
[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Diadema, SP, Brazil
[2] Univ Fed Sao Paulo, Dept Mol Biol, Sao Paulo, SP, Brazil
[3] Natl Inst Mat Sci, Int Ctr Mat Nanoarchitecton WPI MANA, 1-1 Namiki, Tsukuba, Ibaraki 3050044, Japan
[4] Natl Inst Mat Sci, Res Ctr Funct Mat, 1-2-1 Sengen, Tsukuba, Ibaraki 3050047, Japan
[5] Univ Tokyo, Grad Sch Frontier Sci, Dept Adv Mat Sci, 5-1-5 Kashiwanoha, Kashiwa, Chiba 2778561, Japan
基金
巴西圣保罗研究基金会;
关键词
Trastuzumab; Lipid monolayers; Air-water interface; Langmuir films; Cellular membrane; LANGMUIR MONOLAYERS; DRUG-DELIVERY; MEMBRANE; CANCER; LIPOSOMES; SPECTROSCOPY; BIOPHYSICS; AREA;
D O I
10.1016/j.chemphyslip.2020.104875
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Trastuzumab (Tmab), an antibody for breast cancer, was incorporated in Langmuir monolayers with different lipidic compositions to investigate the drug action in lipidic interfaces of pharmaceutical interest. Tmab caused all lipid films to expand as confirmed with by surface pressure-area isotherm, proving its incorporation. It also affected the compressional and structural properties as observed by in-plane elasticity curves and polarization modulation reflection-absorption infrared spectroscopy (PM-IRRAS), respectively. Although Tmab did not change significantly the compressional modulus for dipalmitoylphosphatidylcholine (DPPC) monolayers, it decreased it for the mixtures of DPPC with cholesterol. In contrast, for dipalmitoylphosphoethanolamine (DPPE), Tmab increased the compressional modulus for both monolayers, pure DPPE or mixed with cholesterol. While Brewster Angle Microscopy showed discrete distinctive morphological patterns for the monolayers investigated, PM-IRRAS showed that Tmab caused an increased number of gauche conformers related to the CH2 stretching mode for the lipid acyl chains, suggesting molecular disorder. Furthermore, the antibody kept the (beta-sheet structure of the polypeptide backbone adsorbed at the lipid monolayers although the secondary conformation altered according to the film composition at the air-water interface. As a result, the results suggest that the membrane lipid profile affects the adsorption of Tmab at lipid monolayers, which can be important for the incorporation of this drug in lipidic supramolecular systems like in liposomes for drug delivery and in bio-membranes.
引用
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页数:6
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