TEM1-targeting PEGylated PLGA shikonin nanoformulation for immunomodulation and eradication of ovarian cancer.

Details

Serval ID
serval:BIB_7205BBE80A2D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TEM1-targeting PEGylated PLGA shikonin nanoformulation for immunomodulation and eradication of ovarian cancer.
Journal
BioImpacts
Author(s)
Matthaiou E.I., Guo Y., Barar J., Sandaltzopoulos R., Kandalaft L.E., Li C., Coukos G., Omidi Y.
ISSN
2228-5652 (Print)
ISSN-L
2228-5652
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
12
Number
1
Pages
65-86
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Introduction: Tumor endothelial marker 1 (TEM1) is expressed by tumor vascular endothelial cells in various cancers. Methods: Here, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) PEGylated with polyethylene glycol (PEG) and functionalized with anti-TEM1 antibody fragment (78Fc) and loaded them with necroptosis-inducing agent shikonin (SHK) (78Fc-PLGA-SHK NPs). Results: The nanoformulation showed a smooth spherical shape (~120 nm; the ζ potential of -30 mV) with high drug entrapment and bioconjugation efficiencies (~92% and ~90%, respectively) and a sustained-release profile in serum. Having significant toxicity in vitro (e.g., MS1 and TC1 cells), the nanoformulation dramatically increased the cytotoxicity in the TC1 murine lung carcinoma subcutaneous and intravenous/metastatic models as aggressive tumor models. The injection of the 78Fc-PLGA-SHK NPs to the MS1-xenograft mice resulted in significantly higher accumulation and effects in the TEM1-positive tumor targets, while they were excreted via urine track without retaining in the liver/spleen. In the TC1 subcutaneous model, C57/BL6 mice treated with the 78Fc-PLGA-SHK NPs revealed a significant therapeutic effect. The mice, which were tumor-free after receiving the nanoformulation, were re-challenged with the TC1 cells to investigate the immune response. These animals became tumor-free a week after the injection of TC1 cells. Conclusion: Based on these findings, we propose the 78Fc-PLGA-SHK NPs as a highly effective immunostimulating nanomedicine against the TEM1-expressing cells for targeted therapy of solid tumors including ovarian cancer.
Keywords
CD248, Nanomedicine, Shikonin, Targeted therapy, Tumor endothelial marker 1, endosialin, Tumor vasculature
Pubmed
Web of science
Create date
08/02/2022 10:03
Last modification date
15/07/2022 6:36
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