2022年12月
Disposition of E-selectin-targeting liposomes in tumor spheroids with a perfusable vascular network
Drug Metabolism and Pharmacokinetics
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- 巻
- 47
- 号
- 開始ページ
- 100469
- 終了ページ
- 100469
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.dmpk.2022.100469
- 出版者・発行元
- Elsevier BV
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.
- リンク情報
- ID情報
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- DOI : 10.1016/j.dmpk.2022.100469
- ISSN : 1347-4367
- PubMed ID : 36174354