Folic acid-modified diatrizoic acid-linked dendrimer-entrapped gold nanoparticles enable targeted CT imaging of human cervical cancer

Abstract

It has been a great challenge to develop multifunctional fluorescent nanoprobes for tumor-targeted imaging. In this study, we developed folic acid (FA) gold nanoparticles (AuNPs) through diatrozic acid (DTA) linking for in vitro and in vivo targeted imaging of HeLa cervical cancer cells by computed tomography (CT). G5 dendrimers were used as templates to synthesize AuNPs within the interiors of dendrimers. The synthesized AuNPs were then sequentially modified by fluorescein isothiocyanate, FA, and DTA and the remaining terminal amines on the dendrimers were acetylated. We further performed hematoxylin and eosin staining, cell viability assay, flow cytometric analysis of cell cycle and apoptosis, and hemolytic assay to examine the cytotoxicity and hemocompatibility of the particles. The specific uptake of the nanoparticles by HeLa cells was determined through inductively coupled plasma atomic emission spectroscopy determination of silver and transmission electron microscopy. Lastly, HeLa cells and a xenografted HeLa tumor model were employed to evaluate the in vitro and in vivo targeted CT imaging performances of the nanoparticles, respectively. We showed that Au DENPs-FA-DTA does not cause cytotoxic effects on both HeLa cancer cells and healthy normal cells in mice, demonstrating the superior biocompatibility and stability of the particles in the given concentration range. Micro-CT images documented that HeLa cells incubated with Au DENPs-FA-DTA in vitro could be identified by X-ray examinations and that HeLa cells xenografts in BALB/c nude mice could be imaged after the mice were administered with the particles intravenously or intratumorally. The FA-modified AuNPs enabled targeted CT imaging of HeLa cells overexpressing FA receptors in vitro and in vivo. Taken together, our results showed that the AuNPs we developed exhibit great potentials as imaging probes for targeted CT imaging of human cervical cancer.

Advanced Functional Structure‐Based Sensing and Imaging Strategies for Cancer Detection: Possibilities, Opportunities, Challenges, and Prospects

“…Various targeting agents such as folic acid, hyaluronic acid, and antibodies can be efficiently conjugated with AuNPs for CT imaging of tumors in animal models. [67a,97] The folic acid conjugated modified AuNPs were tested on HeLa cervical cancer bearing mice. [97a] The treatment of AuNPs with folic acid enhanced the targeting efficiency of the CT contrast agent.…”

“…[67a,97] The folic acid conjugated modified AuNPs were tested on HeLa cervical cancer bearing mice. [97a] The treatment of AuNPs with folic acid enhanced the targeting efficiency of the CT contrast agent. The above research articles outlined three conditions for obtaining optimum CT signals using AuNPs: 1) intravenous administration of AuNP‐based contrast agents, 2) CT imaging after 6 h of injection, and 3) use of cancer targeted AuNPs.…”

“…The above research articles outlined three conditions for obtaining optimum CT signals using AuNPs: 1) intravenous administration of AuNP‐based contrast agents, 2) CT imaging after 6 h of injection, and 3) use of cancer targeted AuNPs. [97a] Similarly, hyaluronic acid‐containing CT contrast systems (dendrimer conjugated AuNPs) were also explored for the CT imaging of HCCLM3 tumor cells in mice. [97b] In another report, the sequential modification of AuNPs with fluorescein isothiocyanate, folic acid, and diatrozic acid was performed to target CT imaging of human cervical cancer.…”

“…[97a] Similarly, hyaluronic acid‐containing CT contrast systems (dendrimer conjugated AuNPs) were also explored for the CT imaging of HCCLM3 tumor cells in mice. [97b] In another report, the sequential modification of AuNPs with fluorescein isothiocyanate, folic acid, and diatrozic acid was performed to target CT imaging of human cervical cancer. [97a]…”

“…[97b] In another report, the sequential modification of AuNPs with fluorescein isothiocyanate, folic acid, and diatrozic acid was performed to target CT imaging of human cervical cancer. [97a]…”