Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles

Abstract

Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O’-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.

Peptide-functionalized quantum dots for potential applications in the imaging and treatment of obesity

“…13,[15][16][17] QDs are inorganic fluorescent semiconductor nanoparticles used as labeling and imaging tools in biomedical research. [18][19][20] Unlike organic fluorophores and fluorescent proteins, QDs have a broad excitation spectra, narrow emission spectra, and long fluorescence half-life and can be conjugated to biomolecules, making them excellent probes for bio-imaging applications. [17][18][19][20] The optical properties of QDs are attributed to quantum confinement due to their nanoscale size.…”

“…[18][19][20] Unlike organic fluorophores and fluorescent proteins, QDs have a broad excitation spectra, narrow emission spectra, and long fluorescence half-life and can be conjugated to biomolecules, making them excellent probes for bio-imaging applications. [17][18][19][20] The optical properties of QDs are attributed to quantum confinement due to their nanoscale size. 17 Moreover, their high fluorescence quantum yield and resistance to photo bleaching make them good fluorescent labeling agents for targeted delivery and cellular imaging.…”

Characterization of a DNA Aptamer for Ovarian Cancer Clinical Tissue Recognition and in Vivo Imaging

“…For example, DML-7, an DNA aptamer, binds with prostate cancer (PC) tissue specimens [19]. QD-A32 Apt showed breast cancer-specific accumulation in engrafted mice [31]. However, up to now, there are few studies investigating the use of fluorescent-labeled or gold metal-conjugated aptamers to assess cancer characteristics.…”

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

“…Kim et al 2017 developed a theranostic liposomal system for carrying diagnostic Quantum Dots (QD) and therapeutic siRNA that were coupled to aptamer molecules against EGFR. The theranostic liposomes were evaluated in terms of cancer-targeted siRNA delivery and QD imaging in vitro and in vivo [11]. The anti-EGFR aptamer was used recently as a theranostic delivery system.…”

“…In order to provide targetability, aptamers have been widely used due to (I) their capacity of binding to target proteins with a high affinity and specificity, (II) having already been shown to have antibody-like characteristics, and (III) the fact that they are relatively smaller and less immunogenic. All of these useful properties make aptamers attractive in therapeutic and diagnostic fields [11].…”