Polymeric biocompatible iron oxide nanoparticles labeled with peptides for imaging in ovarian cancer.

Deepshikha Shahdeo,Veerbhan Kesarwani,Raghuraj Singh Chouhan,Milena Horvat,Akanksha Roberts,Sonu Gandhi

doi:10.1042/bsr20212622

Abstract

Compared with other nanomaterials, surface-modified iron oxide nanoparticles (IONPs) have gained attraction for cancer therapy applications due to its low toxicity, and long retention time. An innocuous targeting strategy was developed by generation of fluorescein isothiocyanate (FITC)-labeled peptide (growth factor domain (GFD) and somatomedin B domain (SMB)) functionalized, chitosan-coated IONPs (IONPs/C). It can be used to target urokinase plasminogen activator receptor (uPAR), which is a surface biomarker, in ovarian cancer. Binding affinity between uPAR and peptides (GFD and SMB) were revealed by in-silico docking studies. The biophysical characterizations of IONPs, IONPs/C, and IONPs/C/GFD-FITC or SMB-FITC nanoprobes were assessed via Vibrating Sample Magnetometer (VSM), Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and Fourier Transform Infrared Spectroscopy (FT-IR). Prussian Blue staining, fluorescence spectroscopy, and fluorescence imaging were performed to confirm the targeting of nanoprobes with the surface receptor uPAR. The combination of IONPs/C/GFD+SMB showed efficient targeting of uPAR in the tumor microenvironment, and thus can be implemented as a molecular magnetic nanoprobe for cancer cell imaging and targeting.

Highlights

Cancer remains one of the leading causes of mortality even though substantial advancement in research over the last decades has taken place [1]
Urokinase Plasminogen Activator Receptor that plays a significant role in tissue remodeling, embryogenesis and wound healing is overexpressed in human cancers such as tumors, leukemias, lymphomas indicating invasion and metastasis [3,4,5,6,7]. uPAR belongs to a family of proteins called the lymphocyte antigen 6 which have a globular structure consisting of five to six antiparallel β-strands linked via four to five disulfide bonds [8,9]
The binding affinity of the uPAR–growth factor domain (GFD) complex was significantly reduced when docked with somatomedin B (SMB), with an root-mean-square deviation (RMSD) value of 0.3 and a binding affinity of −623 kcal/mol, indicating a major conformational shift and energy difference in the structure of the uPAR/GFD/SMB complex (Figure 1)

Summary

Introduction

Cancer remains one of the leading causes of mortality even though substantial advancement in research over the last decades has taken place [1]. UPAR belongs to a family of proteins called the lymphocyte antigen 6 which have a globular structure consisting of five to six antiparallel β-strands linked via four to five disulfide bonds [8,9]. Urokinase Plasminogen Activator Receptor (uPAR) that plays a significant role in tissue remodeling, embryogenesis and wound healing is overexpressed in human cancers such as tumors, leukemias, lymphomas indicating invasion and metastasis [3,4,5,6,7]. It comprises three domains; D1, D2, D3 packed together and the central region involves the residues from three domains that binds with uPA at the amino terminal growth factor domain (GFD). Studies have shown that a high level of uPA in tumor tissues could be a powerful prognostic marker for breast cancer [13,14]

Methods

Results

Conclusion