DSPE-PEG(2000)-NHS is a PEGylated phospholipid derivative widely used for liposome preparation and surface modification[1]. As an amphiphilic polymer composed of DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), PEG (polyethylene glycol), and NHS (N-hydroxysuccinimide) groups, DSPE-PEG(2000)-NHS exhibits excellent biocompatibility and low toxicity[2]. The NHS group enables covalent conjugation with amine-containing molecules (e.g., antibodies, peptides), allowing targeted drug delivery applications[3]. DSPE-PEG(2000)-NHS is commonly employed as a linker to functionalize liposome surfaces, enhancing their targeting capabilities and stability in drug delivery systems[4][5].
In vitro, the DSPE-PEG(2000)-NHS-modified peptide marine drug lead, α-conotoxin TxID (DSPE-PEG-TxID), significantly inhibits the α3β4 nicotinic acetylcholine receptor (nAChR) when applied to Xenopus laevis oocytes at a concentration of 10µM for 5 minutes[6].
In vivo, in an SKBR3 breast cancer mouse xenograft model, DSPE-PEG(2000)-NHS-containing liposomes conjugated to the breast cancer-targeting H6 peptide and encapsulating the DNA topoisomerase inhibitor doxorubicin localize to the liver and tumor, significantly reducing tumor growth after intravenous administration of 30µg/day for 6 days[7].
References:
[1] Zhang X, Xie J, Li S, Wang X, Hou X. The study on brain targeting of the amphotericin B liposomes. J Drug Target. 2003;11(2):117-122.
[2] Tong SW, Xiang B, Dong DW, Qi XR. Enhanced antitumor efficacy and decreased toxicity by self-associated docetaxel in phospholipid-based micelles. Int J Pharm. 2012;434(1-2):413-419.
[3] Amaolo A, Sadeghi H, Carrera C, et al. Cellular Uptake of Hybrid PLGA-Lipid Gadolinium Nanoparticles Functionalized for Magnetic Resonance Imaging of Pancreatic Adenocarcinoma Cells. ACS Nanosci Au. 2025;5(3):184-195.
[4] Li X, Li J, Xu J, et al. Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine-Rich Quadruplex Nucleotide-Lipid Derivative for Treatment of Resistant Breast Cancer. Small. 2021;17(13):e2007391.
[5] Mu Y, Wei M, Liu Y, et al. Lactoferrin-functionalized PEGylation liposomes loaded with norcantharidin acid for targeted therapy of hepatocellular carcinoma. Int J Pharm. 2025;671:125245.
[6] Zhao W, Xiong Y, Zhangsun D, Luo S. DSPE-PEG Modification of α-Conotoxin TxID. Mar Drugs. 2019;17(6):342.
[7] Jia X, Wang W, Han Q, Wang Z, Jia Y, Hu Z. Micromixer Based Preparation of Functionalized Liposomes and Targeting Drug Delivery. ACS Med Chem Lett. 2016;7(4):429-434.
DSPE-PEG(2000)-NHS是一种广泛用于脂质体制备和表面修饰的聚乙二醇化磷脂衍生物[1]。作为一种由DSPE（1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺）、PEG（聚乙二醇）和NHS（N-羟基琥珀酰亚胺）基团组成的两亲性聚合物，DSPE-PEG(2000)-NHS具有优异的生物相容性和低毒性[2]。NHS基团能够与含氨基的分子（例如抗体、肽）进行共价结合，从而实现靶向药物递送应用[3]。DSPE-PEG(2000)-NHS）常用作连接分子对脂质体表面进行功能化修饰，增强其在药物递送系统中的靶向能力和稳定性[4][5]。
在体外研究中，经过DSPE-PEG(2000)-NHS修饰的海洋药物先导物——α-芋螺毒素TxID（DSPE-PEG-TxID）在以10µM的浓度作用于非洲爪蟾卵母细胞5分钟时，显著抑制了α3β4型烟碱乙酰胆碱受体（nAChR）的活性[6]。
在体内研究中，在SKBR3乳腺癌小鼠异种移植模型中，含有DSPE-PEG(2000)-NHS、与乳腺癌靶向 H6 肽结合且包封了DNA拓扑异构酶抑制剂阿霉素的脂质体在以30µg/天的剂量静脉注射给药6天后能够靶向富集于肝脏和肿瘤组织，显著抑制肿瘤生长[7]。