Disposition of E-selectin-targeting liposomes in tumor spheroids with a perfusable vascular network.
Drug Metab Pharmacokinet
; 47: 100469, 2022 Dec.
Article
in En
| MEDLINE
| ID: mdl-36174354
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-1ß, 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
E-Selectin
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Drug Metab Pharmacokinet
Journal subject:
FARMACOLOGIA
/
METABOLISMO
Year:
2022
Document type:
Article
Affiliation country: