Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

Abstract

Recent advances in fluorescent metal nanoclusters have spurred tremendous interest in nanomedicine due to the ease of fabrication, excellent biocompatibility, and, more importantly, excellent wavelength-dependent tunability. Herein, we report our findings on fluorescent BSA-protected gold nanoclusters (AuNCs), ∼2 nm in size conjugated with Herceptin (AuNCs-Her), for specific targeting and nuclear localization in ErbB2 over-expressing breast cancer cells and tumor tissue as a novel fluorescent agent for simultaneous imaging and cancer therapy. More interestingly, we found that AuNCs-Her could escape the endolysosomal pathway and enter the nucleus of cancer cells to enhance the therapeutic efficacy of Herceptin. We elucidate the diffusion characteristics (diffusion time and number of diffusers) and concentration of the fluorescing clusters in the nucleus of live cells. Our findings also suggest that the nuclear localization effect of AuNCs-Her enhances the anticancer therapeutic efficacy of Herceptin as evidenced by the induction of DNA damage. This study not only discusses a new nanomaterial platform for nuclear delivery of drugs but also provides important insights on nuclear targeting for enhanced therapy.

Fluorescent Gold Nanoclusters: Promising Fluorescent Probes for Sensors and Bioimaging

“…For the purpose of achieving targeted cell imaging, fluorescent AuNCs can be modified with recognition elements. For example, widely studied cancer cell target molecules including herceptin and folic acid have been used to conjugate BASAuNCs for tumor-targeted bioimaging [135,136].…”

Photoluminescent Gold Nanomaterials as Sensitive Probes

“…To specifically target cancer cells, BSA-Au NCs can be conjugated with recognition elements such as small ligands and antibodies. For example, folic acid-BSA-Au NCs are specific toward cancer cells over-expressed folate receptors [18]. A ratiometric probe using BSA-Au/Ce NCs was developed for monitoring the pH values of HeLa cells [19].…”

Gold Nanoclusters: Nanomedicine Potentials and Applications

“…Over expressed receptors on the surface of cancerous cells can be targeted by nanoconjugated NCs. Conjugation of antibodies (Ab), peptides and polymers facilitate this smart selection of solid tumors in vivo for theranostic application [6].…”

“…They introduced a new nanostructure for fluorescence imaging and nuclear delivery of drugs. The conversion of biocompatible AuNCs to a smart anticancer delivery system decreases cell viability by apoptosis unlike non conjugated AuNCs [6].…”