Gold Nanosystems Covered with Doxorubicin/DNA Complexes: A Therapeutic Target for Prostate and Liver Cancer

Abstract

Different gold nanosystems covered with DNA and doxorubicin (Doxo) were designed and synthesized for cancer therapy, starting from Au@16-Ph-16 cationic nanoparticles and DNA–Doxo complexes prepared under saturation conditions. For the preparation of stable, biocompatible, and small-sized compacted Au@16-Ph-16/DNA–Doxo nanotransporters, the conditions for the DNA–Doxo compaction process induced by gold nanoparticles were first explored using fluorescence spectroscopy, circular dichroism and atomic force microscopy techniques. The reverse process, which is fundamental for Doxo liberation at the site of action, was found to occur at higher CAu@16-Ph-16 concentrations using these techniques. Zeta potential, dynamic light scattering and UV–visible spectroscopy reveal that the prepared compacted nanosystems are stable, highly charged and of adequate size for the effective delivery of Doxo to the cell. This fact is verified by in vitro biocompatibility and internalization studies using two prostate cancer-derived cell lines (LNCaP and DU145) and one hepatocellular carcinoma-derived cell line (SNU-387), as well as a non-tumor prostate (PNT2) cell line and a non-hepatocarcinoma hepatoblastoma cell line (Hep-G2) model used as a control in liver cells. However, the most outstanding results of this work are derived from the use of the CI+NI combined treatments which present strong action in cancer-derived cell lines, while a protective effect is observed in non-tumor cell lines. Hence, novel therapeutic targets based on gold nanoparticles denote high selectivity compared to conventional treatment based on free Doxo at the same concentration. The results obtained show the viability of both the proposed methodology for internalization of compacted nanocomplexes inside the cell and the effectiveness of the possible treatment and minimization of side effects in prostate and liver cancer.

Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance

“…To obtain stable nanocomplexes with gemini surfactant-functionalized AuNPs (Au@16-mph-16) and AMOX, we employed DNA as a linker biomolecule. DNA is a genetic material with high biocompatibility and low cytotoxicity, making it ideal for applications in biomedicine [ 21 , 44 , 50 , 51 , 52 ]. Therefore, its use in the manufacturing of systems for the transport of antimicrobials to the interior of the target could help reduce antimicrobial resistance.…”

“…In addition, the interaction of both the cationic gemini surfactant that constitutes the nanoparticles and the gold core with DNA foments the compaction of the biomolecule itself, facilitating entry to the bacterial interior in its compacted form [ 21 , 44 , 58 ]. Therefore, it is expected that disturbances will appear in the secondary structure of the DNA/AMOX complex in its interaction with AuNPs, which could modify the biochemical and biological effects of free AMOX.…”

“…Visualization of the samples was performed with a Zeiss Libra microscope. For more details, see the protocol followed by the research group in previous works [ 21 , 40 , 44 , 45 , 46 ]. The different samples were studied by observation of between 500 to 700 bacteria per experiment.…”

An updated landscape on nanotechnology-based drug delivery, immunotherapy, vaccinations, imaging, and biomarker detections for cancers: recent trends and future directions with clinical success

“…The increase of PD-1 + CD8 + T cell population from 33.25 to 63.22% in presence of 2.5 µg/mlAuPEIs, in vivo, may increase the therapeutic efficacy of additional anti-PD-1 or anti-PD-L1 antibodies with better anticancer effect. GNPs covered with DOX and DNA were found to be equally effective in the annihilation of both prostate and liver cancer cells, in vitro [ 61 ]. Here DNA was used to induce various conformational changes in the GNP-DOX complex, thereby increasing its efficacy.…”

The Anticancer Drug Daunomycin Directly Affects Gene Expression and DNA Structure

“…Daunomycin (DM), also known as daunorubicin, is an anthracycline antibiotic widely used over the past half-century to treat various cancers such as leukemia and lymphoma [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ] and is found on the WHO Model Lists of Essential Medicines [ 12 ]. Despite its useful potency for cancer therapy, the application of DM for wider use as an anticancer drug is limited due to its serious side effects, including fatal cardiac toxicity.…”