Attaching folic acid on gold nanoparticles using noncovalent interaction via different polyethylene glycol backbones and targeting of cancer cells

Bhattacharya, Resham; Patra, Chitta Ranjan; Earl, Alexis; Wang, Shanfeng; Katarya, Aaron; Lu, Lichun; Kizhakkedathu, Jayachandran N.; Yaszemski, Michael J.; Greipp, Philip R.; Mukhopadhyay, Debabrata; Mukherjee, Priyabrata

doi:10.1016/j.nano.2007.07.001

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 3, Issue 3 , Pages 224-238, September 2007

Attaching folic acid on gold nanoparticles using noncovalent interaction via different polyethylene glycol backbones and targeting of cancer cells

Resham Bhattacharya, MS, PhD
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Both the authors contributed equally to this work.
Chitta Ranjan Patra, MS, PhD
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Both the authors contributed equally to this work.
Alexis Earl
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Shanfeng Wang, MS, PhD
- Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Aaron Katarya
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Lichun Lu, BEng, PhD
- Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Jayachandran N. Kizhakkedathu, MS, PhD
- Department of Pathology and Laboratory Medicine, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
Michael J. Yaszemski, MD, PhD
- Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Philip R. Greipp, BS, MD
- Division of Hematology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Debabrata Mukhopadhyay, MS, PhD
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Priyabrata Mukherjee, MS, PhD
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Department of Biomedical Engineering, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Corresponding author. Department of Biomedical Engineering and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Received 29 March 2007; accepted 10 July 2007. published online 17 August 2007.

Abstract

This article reports a simple one-step method of attaching folic acid (FA) to gold nanoparticles (AuNPs) and its fine tuning using different polyethylene glycol (PEG) backbones. PEG backbones used in this study are PEG-diamine with molecular weights 2000 (PAM2-2K) and 10,000 (PAM2-10K), PEG-tetramine with molecular weight 20,000 (PAM4-20K), and PEG-dithiol with molecular weight 2000 (PSH2-2K). The nanoconjugates were characterized with ultraviolet-visible spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis, Fourier transform infrared spectroscopy, inductively coupled plasma analysis, and radioactivity measurement with a scintillation counter. Attachment and release profiles of FAs from the nanoconjugates are done using ³H-labelled FAs (³FA). The binding of ³FA follows the order Au-PAM4-20K > Au-PAM2-10K > Au-PAM2-2K > Au > Au-PSH2-2K, whereas its release profile follows the reverse order. Au-PAM4-20K-FA has been used for folate receptor (FR)–mediated targeting of AuNPs to cancer cells. Seven different cancer cell lines (SKOV-3, OVCAR-5, OV-202, OV-167, OPM-1, RPMI, and U266) were screened for expression of FRs. Among ovarian cancer cells, the expression pattern of FRs follows the order OV-167 > SKOV-3 > OV-202 > OVCAR-5, and multiple myeloma cell lines follow the order OPM-1 > U266 > RPMI. Intracellular uptakes of the nanoconjugates containing FA or no FA were monitored with digital optical photography and TEM. Quantitation of the internalization of nanoconjugates in different cell lines was determined by gold analysis with inductively coupled plasma. It is found that the uptake of the nanoconjugates correlates with FR expression. Maximum uptake is observed for OV-167, whereas it is minimum for OVCAR-5. TEM images of the cells treated with Au-PAM4-20K-FA confirm the endocytosis of the nanoconjugates. This study is an important step for targeted delivery of anticancer drugs as well as metal nanoparticles for targeted therapy, tumor imaging, and ablation exploiting the overexpression of FRs on cancer cells.

Key words: Gold nanoparticles, Folic acid, Ovarian cancer, Multiple myeloma, Targeting