Logo-bi
Bioimpacts. 2022;12(1): 65-86.
doi: 10.34172/bi.2021.23511
PMID: 35087718
PMCID: PMC8783079
Scopus ID: 85127176631
  Abstract View: 644
  PDF Download: 403
  Full Text View: 311

Original Research

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

Efthymia-Iliana Matthaiou 1,2 ORCID logo, Yi Guo 1,3, Jaleh Barar 1,4 ORCID logo, Raphael Sandaltzopoulos 2, Lana E. Kandalaft 5, Chunsheng Li 1*, George Coukos 1,5, Yadollah Omidi 1,6* ORCID logo

1 Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
2 Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece
3 University of Shanghai, Shanghai, China
4 Research Center for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5 Ludwig Institute for Cancer Research, Lausanne and University of Lausanne, Lausanne, Switzerland
6 Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
*Corresponding Authors: Corresponding authors: Chunsheng Li, Email: chunsheng.li.phd@gmail.com; Yadollah Omidi, Email: yomidi@nova.edu, Email: chunshengliphd@gmail.com; Email: yomidi@nova.edu

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.

First Name
Last Name
Email Address
Comments
Security code


Abstract View: 644

Your browser does not support the canvas element.


PDF Download: 403

Your browser does not support the canvas element.


Full Text View: 311

Your browser does not support the canvas element.

Submitted: 16 Nov 2020
Revision: 01 Dec 2021
Accepted: 08 Dec 2021
ePublished: 19 Dec 2021
EndNote EndNote

(Enw Format - Win & Mac)

BibTeX BibTeX

(Bib Format - Win & Mac)

Bookends Bookends

(Ris Format - Mac only)

EasyBib EasyBib

(Ris Format - Win & Mac)

Medlars Medlars

(Txt Format - Win & Mac)

Mendeley Web Mendeley Web
Mendeley Mendeley

(Ris Format - Win & Mac)

Papers Papers

(Ris Format - Win & Mac)

ProCite ProCite

(Ris Format - Win & Mac)

Reference Manager Reference Manager

(Ris Format - Win only)

Refworks Refworks

(Refworks Format - Win & Mac)

Zotero Zotero

(Ris Format - Firefox Plugin)