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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Bioimpacts. 2022 ;12(1):65-86. Epub 2021 Dec 19. PMID: 35087718

Abstract Author(s):

Efthymia-Iliana Matthaiou, Yi Guo, Jaleh Barar, Raphael Sandaltzopoulos, Lana E Kandalaft, Chunsheng Li, George Coukos, Yadollah Omidi

Article Affiliation:

Efthymia-Iliana Matthaiou

Abstract:

Tumor endothelial marker 1 (TEM1) is expressed by tumor vascular endothelial cells in various cancers.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).The nanoformulation showed a smooth spherical shape (~120 nm; theζ 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 lungcarcinoma 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.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.

Study Type : Animal Study, In Vitro Study
Additional Links
Pharmacological Actions : Immunomodulatory : CK(4048) : AC(2154)

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