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

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

Research output: Contribution to journalArticle

145 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)224-238
Number of pages15
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2007

Keywords

  • Folic acid
  • Gold nanoparticles
  • Multiple myeloma
  • Ovarian cancer
  • Targeting

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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