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:
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[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.