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基于 Tuftsin 修饰的脂质体靶向药物递送:在传染病和肿瘤治疗中的应用。

Targeted Drug Delivery Using Tuftsin-bearing Liposomes: Implications in the Treatment of Infectious Diseases and Tumors.

机构信息

Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.

出版信息

Curr Drug Targets. 2021;22(7):770-778. doi: 10.2174/1389450121999201125200756.

Abstract

Tuftsin, a tetrapeptide (Thr-Lys-Pro-Arg), acts as an immunopotentiating molecule with its ability to bind and activate many immune cells, including macrophages or monocytes, neutrophils and dendritic cells. The specific targeting activity of tuftsin has been further increased by its palmitoylation followed by its incorporation into the lipid bilayer of liposomes. Tuftsin-bearing liposomes (Tuft-liposomes) possess several characteristics that enable them to act as a potential drug and vaccine carriers. Tuft-liposomes-loaded anti-microbial drugs have been shown to be highly effective against many infectious diseases, including tuberculosis, leishmaniasis, malaria, candidiasis and cryptococosis. Moreover, Tuft-liposomes also increased the activity of anticancer drug etoposide against fibrosarcoma in mice. Tuft-liposomes showed the immune-potentiating effect and rejuvenated the immune cells in the leukopenic mice. In addition, antigens encapsulated in Tuftsin-bearing liposomes demonstrated greater immunogenicity by increasing the T cell proliferation and antibody secretion. Keeping into consideration their specific targeting and immunopotentiating effects, Tuft-liposomes may potentially be used as promising drug and vaccine delivery systems.

摘要

四肽(Thr-Lys-Pro-Arg)促缚素作为一种免疫增强分子,能够结合并激活多种免疫细胞,包括巨噬细胞或单核细胞、中性粒细胞和树突状细胞。促缚素的棕榈酰化及其随后被整合到脂质体的双层脂质中,进一步提高了其特异性靶向活性。携带促缚素的脂质体(Tuft-liposomes)具有多种特性,使其能够作为潜在的药物和疫苗载体。携带促缚素的脂质体负载的抗微生物药物已被证明对许多传染病具有高度疗效,包括结核病、利什曼病、疟疾、念珠菌病和隐球菌病。此外,Tuft-liposomes 还增加了抗癌药物依托泊苷对小鼠纤维肉瘤的活性。Tuft-liposomes 显示出免疫增强作用,并使白细胞减少症小鼠的免疫细胞恢复活力。此外,包封在携带促缚素的脂质体中的抗原通过增加 T 细胞增殖和抗体分泌显示出更强的免疫原性。考虑到其特异性靶向和免疫增强作用,Tuft-liposomes 可能有希望作为有前途的药物和疫苗传递系统。

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