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咪唑离子液体的细胞毒性评估及其在含紫罗碱靶向药物载体中的包封

Assessment of cytotoxicity of imidazole ionic liquids and inclusion in targeted drug carriers containing violacein.

作者信息

Rivero Berti Ignacio, Rodenak-Kladniew Boris, Onaindia Celeste, Adam Claudia G, Islan German A, Durán Nelson, Castro Guillermo R

机构信息

Laboratorio de Nanobiomateriales, CINDEFI, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET (CCT La Plata) Calle 47 y 115 B1900AJL La Plata Argentina

Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas B1900 La Plata Argentina.

出版信息

RSC Adv. 2020 Aug 10;10(49):29336-29346. doi: 10.1039/d0ra05101b. eCollection 2020 Aug 5.


DOI:10.1039/d0ra05101b
PMID:35521105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9055966/
Abstract

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic. However, violacein is insoluble under physiological conditions preventing its potential therapeutic uses. Surface-active ionic liquids (SAILs) based on the cation 1-alkylimidazolium ([C Him]) with = 10 to 16 alkyl carbon side chain lengths and acetate, bromide, methanesulfonate (S) or trifluoroacetate (F) as counterions were synthesized and screened to dissolve Viol in micellar aqueous media and for toxicological studies on the human lung carcinoma A549 cell line. Screening allowed the selection of 1.5 × 10% (w/v) [CHim]-S because it combines low cytotoxicity with 71.5% cell viability and good interaction with 95.2% of the violacein kept in micellar solution for at least 48 h. [Viol-([CHim]-S)] complex was used to develop an efficient hybrid solid lipid nanoparticle (SLN) carrier based on myristyl myristate and poloxamer 188 and tailored with folate to target cancer cells. Cellular SLN uptake was evaluated with fluorescent DiOC on A549, HCT-116, and HeLa cell lines expressing or not the folate receptor. The results showed fivefold incorporation of Viol nanoparticles in HCT-116 and HeLa cell cultures, displaying a high level of folate receptor. Biophysical characterization of the hybrid solid lipid carrier containing Viol was performed by dynamic light scattering, Fourier transform infrared, X-ray diffraction and X-ray photoelectron spectroscopies, and by transmission electron and cryo-transmission microscopies.

摘要

紫菌素(Viol)是由几种革兰氏阴性细菌产生的一种色素,具有多种生物活性,如抗癌、杀毒和抗寄生虫活性。然而,紫菌素在生理条件下不溶,这限制了其潜在的治疗用途。合成并筛选了基于阳离子1-烷基咪唑鎓([C Him])(烷基碳侧链长度n = 10至16)以及醋酸根、溴离子、甲磺酸盐(S)或三氟醋酸盐(F)作为抗衡离子的表面活性离子液体(SAILs),以在胶束水介质中溶解紫菌素,并用于对人肺癌A549细胞系进行毒理学研究。筛选后选择了1.5×10%(w/v)的[C Him]-S,因为它兼具低细胞毒性(细胞活力为71.5%)以及与95.2%的紫菌素在胶束溶液中保持至少48小时的良好相互作用。[紫菌素-([C Him]-S)]复合物被用于开发一种基于肉豆蔻酸肉豆蔻酯和泊洛沙姆188的高效混合固体脂质纳米颗粒(SLN)载体,并通过叶酸进行修饰以靶向癌细胞。使用荧光DiOC对表达或不表达叶酸受体的A549、HCT-116和HeLa细胞系评估细胞对SLN的摄取情况。结果显示,在表达高水平叶酸受体的HCT-116和HeLa细胞培养物中,紫菌素纳米颗粒的摄取量增加了五倍。通过动态光散射、傅里叶变换红外光谱、X射线衍射和X射线光电子能谱以及透射电子显微镜和低温透射显微镜对含有紫菌素的混合固体脂质载体进行了生物物理表征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/56cd38c468b7/d0ra05101b-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/f8fc37b969c3/d0ra05101b-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/f6adc9db4535/d0ra05101b-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/ffcfd5b06ac6/d0ra05101b-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/e3a900a7f564/d0ra05101b-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/459b2d238852/d0ra05101b-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/55a3a5a3fc2b/d0ra05101b-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/5a06e844de2d/d0ra05101b-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/56cd38c468b7/d0ra05101b-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/f8fc37b969c3/d0ra05101b-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/f6adc9db4535/d0ra05101b-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/ffcfd5b06ac6/d0ra05101b-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/e3a900a7f564/d0ra05101b-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/459b2d238852/d0ra05101b-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/55a3a5a3fc2b/d0ra05101b-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/5a06e844de2d/d0ra05101b-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed31/9055966/56cd38c468b7/d0ra05101b-f8.jpg

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引用本文的文献

[1]
Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines.

J Cancer Res Clin Oncol. 2023-10

[2]
Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity.

Front Chem. 2022-7-7

[3]
Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers.

Front Chem. 2020-11-26

本文引用的文献

[1]
Chromobacterium violaceum delivers violacein, a hydrophobic antibiotic, to other microbes in membrane vesicles.

Environ Microbiol. 2020-1-2

[2]
The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8.

Sci Rep. 2019-9-20

[3]
Violacein Targets the Cytoplasmic Membrane of Bacteria.

ACS Infect Dis. 2019-4-12

[4]
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2018-9-12

[5]
Antiplasmodial and trypanocidal activity of violacein and deoxyviolacein produced from synthetic operons.

BMC Biotechnol. 2018-4-11

[6]
Dual targeting system by supramolecular complex of folate-conjugated methyl-β-cyclodextrin with adamantane-grafted hyaluronic acid for the treatment of colorectal cancer.

Int J Biol Macromol. 2018-2-24

[7]
Development and tailoring of hybrid lipid nanocarriers.

Curr Pharm Des. 2017-11-14

[8]
Antibacterial mode of action of violacein from Chromobacterium violaceum UTM5 against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA).

Environ Sci Pollut Res Int. 2017-3-31

[9]
Infrared Spectroscopy of Ionic Liquids Consisting of Imidazolium Cations with Different Alkyl Chain Lengths and Various Halogen or Molecular Anions with and without a Small Amount of Water.

J Phys Chem B. 2017-3-31

[10]
Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: A review.

Biotechnol Adv. 2016-6-8

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