Elimination of Tumor Cells Using Folate Receptor Targeting by Antibody‐Conjugated, Gold‐Coated Magnetite Nanoparticles in a Murine Breast Cancer Model

Abstract

Background. The chemotherapeutic treatment of cancer suffers from poor specificity for targeting the tumor cells and often results in adverse effects such as systemic toxicity, damage to nontarget tissues, and development of drug-resistant tumors in patients. Increasingly, drug nanocarriers have been explored as a way of lessening or overcoming these problems. In this study, antibody-conjugated Au-coated magnetite nanoparticles, in conjunction with inductive heating produced by exposure to an oscillating magnetic field (OMF), were evaluated for their effects on the viability of tumor cells in a murine model of breast cancer. Treatment effects were evaluated by light microscopy and SEM.Results. 4T1 mammary epithelial carcinoma cells overexpressing the folate receptor were targeted with an anti-folate receptor primary antibody, followed by labeling with secondary antibody-conjugated Au-coated magnetite nanoparticles. In the absence of OMF exposure, nanoparticle labeling had no effect on 4T1 cell viability. However, following OMF treatment, many of the labeled 4T1 cells showed extensive membrane damage by SEM analysis, and dramatically reduced viability as assessed using a live/dead staining assay.Conclusions. These results demonstrate that Au-coated magnetite targeted to tumor cells through binding to an overexpressed surface receptor, in the presence of an OMF, can lead to tumor cell death.

Engineering folate-targeting diselenide-containing triblock copolymer as a redox-responsive shell-sheddable micelle for antitumor therapy in vivo

“…Diselenide enhances targeted release of PTX in the cytoplasm of cancerous cells owing to its sensitivity to a thiol-rich and oxidative-rich environment. The improved toxicity of PTX-loaded PCL-(SeSe-PEG-FA) 2 compared to the nonfolate targeted version was attributed to the higher binding affinity of folate-decorated micelles to folate receptor (FR)-expressing 4T1 breast cancer cells[53].We observed a greater cellular inhibition of PTX-loaded PCL-(SeSe-PEG-FA)2 compared to PTX-loaded PCL-(SeSe-mPEG) 2 (p<0.05). At the 10 nM concentration, PTX-loaded PCL-(SeSe-mPEG) 2 reduced cell viability by approximately 50%, whereas PTX-loaded PCL-(SeSe-PEG-FA) 2 reduced cell viability by approximately 35% (P<0.01).…”

Nanoparticles for imaging and treatment of metastatic breast cancer

“…In the absence of AMF exposure, NPs had no effect on 4T1 cell viability. [75] The photothermal effects were also combined with chemotherapy and radiotherapy for improved therapeutic outcomes. An imageable and photothermal Abraxane-like nanodrug was developed by incorporating PTX and indocyanine green onto albumin to form NPs.…”

Multiple Morphologies of Gold–Magnetite Heterostructure Nanoparticles are Effectively Functionalized with Protein for Cell Targeting

“…Au was deposited on Fe 3 O 4 nanoparticles in a manner similar to that described in previous reports (Lyon et al, 2004; Krystofiak et al, 2012). Fe 3 O 4 nanoparticles were aged at least 3 days at 4°C in 0.1 M TMAOH and then diluted 100-fold in 0.00275% hydrazine hydrate (Sigma-Aldrich).…”

“…In this work, we synthesized gold–iron oxide heterostructure nanoparticles using a typical aqueous method (Lyon et al, 2004; Krystofiak et al, 2012) for synthesis of core–shell nanoparticles. Characterization of the synthesized particles via high-resolution electron microscopy, diffraction, and spectroscopy revealed particle morphologies substantially different from the nominal core–shell structure, but in agreement with expectations from the surface and interface energies.…”

“…In this work, we synthesized gold-iron oxide heterostructure nanoparticles using a typical aqueous method Lyon et al, 2004;Krystofiak et al, 2012! for synthesis of core-shell nanoparticles.…”