Disposition of E-selectin-targeting liposomes in tumor spheroids with a perfusable vascular network. (December 2022)

• Record Type: Journal Article
• Authors: Chantarasrivong, Chanikarn; Okada, Ryu; Yamane, Yuuki; Yang, Xue; Higuchi, Yuriko; Konishi, Miku; Komura, Naoko; Ando, Hiromune; Yokokawa, Ryuji; Yamashita, Fumiyoshi
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 47(2022)
• Publication Date: 2022-12
• Subjects: Liposomes -- Tumor vasculature targeting -- E-selectin -- Sialyl Lewis X mimic -- Vascular-perfusable tumor spheroids -- Microfluidic device; EPR enhanced permeability and retension -- HUVECs human umbilical vein endothelial cells -- nhLFs normal human lung fibroblasts -- 3′-CE sLeX 3′-(1-carboxy)ethyl-sialyl Lewis X -- DSPC distearoylphosphatidylcholine -- PBS phosphate buffered saline; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2022.100469
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: We constructed tumor spheroids with a perfusable vascular network to assess drug delivery systems that target the tumor vasculature. A tricultured tumor spheroid containing human umbilical vein endothelial cells (HUVECs) was placed in the central compartment of a microfluidic device, and the HUVECs were seeded into the microslit channels on both sides. Angiogenic sprouts began to form within a few days, from both the tumor spheroids and microchannels, and became more abundant and branched, while attracting each other, over time. A continuous vascular network of HUVECs was fully formed on Day 7. The uptake of 3′-(1-carboxy)ethyl sialyl Lewis X mimic (3′-CE sLeX mimic) liposomes, which have previously been proven to recognize E-selectin, in vascular-perfusable tumor spheroids was assessed. 3′-CE sLeX mimic and pegylated liposomes were rarely taken up, but when the vascular network was pretreated with TNF-α and IL-1β, 3′-CE sLeX mimic liposomes accumulated considerably more in endothelial cells and their vicinity. Taken together, along with the known in vivo expression of E-selectin in tumor angiogenic blood vessels, these results suggest that 3′-CE sLeX mimic liposomes are a promising carrier for targeting tumor vasculature. Furthermore, proinflammatory cytokine treatment may be appropriate for use with vascular-perfusable tumor spheroids in pharmacokinetic studies. Graphical abstract: Image 1