一种将肽配体的末端胺与胆固醇偶联的新方法：合成iRGD-胆固醇。
A novel method for conjugating the terminal amine of peptide ligands to cholesterol: synthesis iRGD-cholesterol.
作者信息
Fete Matthew G, Betker Jamie L, Shoemaker Richard K, Anchordoquy Thomas J
机构信息
School of Pharmacy, Rueckert-Hartman College, Regis University, 3333 Regis Blvd, Denver, CO 80221 USA.
Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd, Aurora, CO 80045 USA.
出版信息
Ther Deliv. 2019 Jan;10(1):11-20. doi: 10.4155/tde-2018-0057.
Abstract
AIM
Conventional conjugation reactions often involve the use of activated PEG as a linker, but concerns about PEG-mediated reduction in intracellular delivery and enhanced immunogenicity have generated interest in developing methods that eliminate the need for a PEG linker.
MATERIALS & METHODS: Reaction conditions were identified that specifically couples the terminal amine of a cyclic iRGD peptide (CRGDRGPDC) to the hydroxyl moiety of cholesterol through a short carbamate linker.
RESULTS & CONCLUSION: Using this method for synthesizing iRGD-cholesterol, peptide ligands can be incorporated into lipid-based delivery systems, thereby eliminating concerns about adverse reactions to PEG. Toxicity and stability data indicate low toxicity and adequate serum stability at low ligand levels.
摘要
目的
传统的共轭反应通常涉及使用活化的聚乙二醇（PEG）作为连接子，但对PEG介导的细胞内递送减少和免疫原性增强的担忧引发了人们对开发无需PEG连接子的方法的兴趣。
材料与方法
确定了反应条件，通过短氨基甲酸酯连接子将环化整合素靶向配体iRGD肽（CRGDRGPDC）的末端胺与胆固醇的羟基部分特异性偶联。
结果与结论
使用这种合成iRGD-胆固醇的方法，肽配体可以被整合到基于脂质的递送系统中，从而消除了对PEG不良反应的担忧。毒性和稳定性数据表明，在低配体水平下具有低毒性和足够的血清稳定性。
相似文献
1
A novel method for conjugating the terminal amine of peptide ligands to cholesterol: synthesis iRGD-cholesterol.一种将肽配体的末端胺与胆固醇偶联的新方法：合成iRGD-胆固醇。
Ther Deliv. 2019 Jan;10(1):11-20. doi: 10.4155/tde-2018-0057.
2
Failure of active targeting by a cholesterol-anchored ligand and improvement by altering the lipid composition to prevent ligand desorption.通过改变脂质组成来防止配体解吸，从而改善胆固醇锚定配体的主动靶向失败。
Int J Pharm. 2018 Jan 30;536(1):42-49. doi: 10.1016/j.ijpharm.2017.11.010. Epub 2017 Nov 7.
3
[Cellular toxicity and anti-tumor efficacy of iRGD modified doxorubixin loaded sterically stabilized liposomes].iRGD修饰的载阿霉素空间稳定脂质体的细胞毒性和抗肿瘤疗效
Yao Xue Xue Bao. 2013 Mar;48(3):417-22.
4
Liposomes co-modified with cholesterol anchored cleavable PEG and octaarginines for tumor targeted drug delivery.用胆固醇锚定的可裂解聚乙二醇和八聚精氨酸共修饰的脂质体用于肿瘤靶向药物递送。
J Drug Target. 2014 May;22(4):313-26. doi: 10.3109/1061186X.2013.875029. Epub 2014 Jan 9.
5
iRGD-coupled responsive fluorescent nanogel for targeted drug delivery.iRGD 偶联的响应性荧光纳米凝胶用于靶向药物递送。
Biomaterials. 2013 Apr;34(13):3523-33. doi: 10.1016/j.biomaterials.2013.01.083. Epub 2013 Feb 12.
6
iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells.iRGD偶联的DSPE-PEG2000纳米胶束用于靶向递送沙利霉素，以治疗肝癌细胞和癌症干细胞。
Nanomedicine (Lond). 2015;10(17):2677-95. doi: 10.2217/nnm.15.106. Epub 2015 Sep 10.
7
iRGD-functionalized PEGylated nanoparticles for enhanced colon tumor accumulation and targeted drug delivery.iRGD 功能化的聚乙二醇化纳米颗粒用于增强结肠肿瘤积累和靶向药物递送。
Nanomedicine (Lond). 2017 Aug;12(16):1991-2006. doi: 10.2217/nnm-2017-0107. Epub 2017 Jul 26.
8
α, ω-Cholesterol-functionalized low molecular weight polyethylene glycol as a novel modifier of cationic liposomes for gene delivery.α,ω-胆固醇功能化的低分子量聚乙二醇作为用于基因递送的阳离子脂质体的新型修饰剂。
Int J Mol Sci. 2014 Nov 6;15(11):20339-54. doi: 10.3390/ijms151120339.
9
Study on galactose-poly(ethylene glycol)-poly(L-lysine) as novel gene vector for targeting hepatocytes in vitro.体外靶向肝细胞的新型基因载体半乳糖-聚乙二醇-聚(L-赖氨酸)的研究。
J Biomater Sci Polym Ed. 2012;23(5):677-95. doi: 10.1163/092050611X558297. Epub 2011 Mar 4.
10
iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer.iRGD 导向的二氧化硅/金纳米颗粒用于高效肿瘤靶向和增强乳腺癌的抗肿瘤疗效。
Int J Nanomedicine. 2024 Aug 12;19:8237-8251. doi: 10.2147/IJN.S474135. eCollection 2024.
引用本文的文献
1
The Effect of Repeat Administration of Lipoplexes on Gene Delivery, Biodistribution, and Cytokine Response in Immunocompetent Tumor-Bearing Mice.脂质体重复给药对免疫功能正常荷瘤小鼠基因传递、生物分布和细胞因子反应的影响。
J Pharm Sci. 2022 Jul;111(7):1926-1936. doi: 10.1016/j.xphs.2021.12.017. Epub 2021 Dec 18.
2
The Use of Lactose as an Alternative Coating for Nanoparticles.乳糖作为纳米粒子替代包衣的应用。
J Pharm Sci. 2020 Apr;109(4):1573-1580. doi: 10.1016/j.xphs.2020.01.019. Epub 2020 Jan 28.
3
The Potential of Exosomes From Cow Milk for Oral Delivery.牛乳来源外泌体的口服递送潜力。
J Pharm Sci. 2019 Apr;108(4):1496-1505. doi: 10.1016/j.xphs.2018.11.022. Epub 2018 Nov 20.
本文引用的文献
1
Targeting peptide iRGD-conjugated amphiphilic chitosan-co-PLA/DPPE drug delivery system for enhanced tumor therapy.靶向肽iRGD偶联的两亲性壳聚糖-共-PLA/DPPE药物递送系统用于增强肿瘤治疗
J Mater Chem B. 2014 Jun 7;2(21):3232-3242. doi: 10.1039/c3tb21744b. Epub 2014 Apr 17.
2
Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin.长期使用大剂量累积的聚乙二醇化脂质体阿霉素未出现心脏毒性。
Cancer Chemother Pharmacol. 2017 Oct;80(4):737-743. doi: 10.1007/s00280-017-3412-8. Epub 2017 Aug 11.
3
Modern Management of Anthracycline-Induced Cardiotoxicity in Lymphoma Patients: Low Occurrence of Cardiotoxicity with Comprehensive Assessment and Tailored Substitution by Nonpegylated Liposomal Doxorubicin.淋巴瘤患者蒽环类药物所致心脏毒性的现代管理：通过综合评估和非聚乙二醇化脂质体阿霉素的个体化替代，心脏毒性发生率较低
Oncologist. 2017 Apr;22(4):422-431. doi: 10.1634/theoncologist.2016-0289. Epub 2017 Mar 8.
4
Nonadditive Effects of Repetitive Administration of Lipoplexes in Immunocompetent Mice.免疫活性小鼠中重复给予脂质体复合物的非加性效应。
J Pharm Sci. 2017 Mar;106(3):872-881. doi: 10.1016/j.xphs.2016.11.013. Epub 2016 Nov 22.
5
Pre-existing anti-PEG antibodies are associated with severe immediate allergic reactions to pegnivacogin, a PEGylated aptamer.预先存在的抗聚乙二醇（PEG）抗体与对聚乙二醇化适体培格尼伐汀的严重速发型过敏反应相关。
J Allergy Clin Immunol. 2016 Dec;138(6):1712-1715. doi: 10.1016/j.jaci.2016.04.058. Epub 2016 Jul 14.
6
Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin.比较脂质体与常规非脂质体阿霉素抗癌疗效的临床前和临床研究的荟萃分析。
J Control Release. 2016 Jun 28;232:255-64. doi: 10.1016/j.jconrel.2016.04.028. Epub 2016 Apr 22.
7
Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer.预先存在的抗聚乙二醇抗体与对聚乙二醇化RNA适体培格尼西的首次暴露过敏反应有关。
J Allergy Clin Immunol. 2016 May;137(5):1610-1613.e7. doi: 10.1016/j.jaci.2015.10.034. Epub 2015 Dec 11.
8
Effect of charge ratio on lipoplex-mediated gene delivery and liver toxicity.电荷比对脂质体介导的基因递送及肝脏毒性的影响。
Ther Deliv. 2015;6(11):1243-53. doi: 10.4155/tde.15.77. Epub 2015 Nov 26.
9
Relating toxicity to transfection: using sphingosine to maintain prolonged expression in vitro.将毒性与转染相关联：利用鞘氨醇在体外维持长期表达。
Mol Pharm. 2015 Jan 5;12(1):264-73. doi: 10.1021/mp500604r. Epub 2014 Dec 3.
10
Potential induction of anti-PEG antibodies and complement activation toward PEGylated therapeutics.对聚乙二醇化治疗药物产生抗聚乙二醇抗体和补体激活的潜在诱导作用。
Drug Discov Today. 2014 Dec;19(12):1945-52. doi: 10.1016/j.drudis.2014.08.015. Epub 2014 Sep 7.
Zotero 插件