A novel and easy to prepare azo-based bioreductive linker and its application in hypoxia-sensitive cationic liposomal doxorubicin: Synthesis, characterization, in vitro and in vivo studies in mice bearing C26 tumor

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mohammad Mashreghi , Mahdi Faal Maleki , Anis Askarizadeh , Helaleh Farshchi , Leila Farhoudi , Mahda Sadat Nasrollahzadeh , Mahere Rezazade Bazaz , Farzin Hadizadeh , Mahmoud Reza Jaafari
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引用次数: 1

Abstract

This study designed and synthesized a cost-effective azo-based hypoxia-sensitive linker (AHSL) using commercially accessible, inexpensive raw materials and simple methods to apply in cationic nanoliposomes. Then, AHSL was post-inserted into the cationic liposome (Cat-lip), and PEG-Azo-Cat-lip was prepared and characterized using DLS. The decrease in the zeta-potential of formulation from + 18.4 mV for Cat-lip to + 6.1 mV and the increase in the size of the PEG-Azo-Cat-lip indicated the successful post insertion of AHSL into the liposomes. The Doxorubicin (Dox) release study showed that PEGylation results in a more stable PEG-Azo-Cat-lip than the Cat-lip. The increased cytotoxicity of the PEG-Azo-Cat-lip in the hypoxic condition also indicated the cleavage of the AHSL in the hypoxic environment. In vivo biodistribution using animal imaging has shown higher tumor accumulation of the MPEG-Azo-Cat-lip than Cat-lip during the 120 h of the study. The results of anti-tumor activities and biosafety of the formulations also showed the higher efficiency of the MPEG-Azo-Cat-lip compared with the Cat-lip. The results of this study indicated the antitumor efficacy of this hypoxia-sensitive which merits further investigation.

Abstract Image

一种易于制备的新型偶氮基生物还原连接剂及其在低氧敏感阳离子脂质体阿霉素中的应用:C26肿瘤小鼠的合成、表征及体内外实验研究
本研究设计并合成了一种具有成本效益的偶氮基低氧敏感连接剂(AHSL),该连接剂采用商业上可获得的廉价原料和简单的方法应用于阳离子纳米脂质体。然后,将AHSL后插入阳离子脂质体(Cat-lip)中,制备PEG-Azo-Cat-lip,并用DLS对其进行表征。Cat-lip的zeta电位从+ 18.4 mV降至+ 6.1 mV, peg -偶氮猫唇的大小增加,表明AHSL成功插入脂质体。阿霉素(Dox)释放研究表明,聚乙二醇化产生的peg -偶氮猫唇比猫唇更稳定。PEG-Azo-Cat-lip在缺氧条件下的细胞毒性增加也表明了AHSL在缺氧环境下的分裂。动物成像的体内生物分布显示,在研究的120小时内,MPEG-Azo-Cat-lip的肿瘤蓄积高于Cat-lip。在抗肿瘤活性和生物安全性方面,MPEG-Azo-Cat-lip的效率高于Cat-lip。本研究结果表明,这种低氧敏感植物的抗肿瘤作用值得进一步研究。
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来源期刊
Chemistry and Physics of Lipids
Chemistry and Physics of Lipids 生物-生化与分子生物学
CiteScore
7.60
自引率
2.90%
发文量
50
审稿时长
40 days
期刊介绍: Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.
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