Biocompatible DNA/5-Fluorouracil-Gemini Surfactant-Functionalized Gold Nanoparticles as Promising Vectors in Lung Cancer Therapy

Abstract

The design and preparation of novel nanocarriers to transport cancer drugs for chemotherapy purposes is an important line of research in the medical field. A new 5-fluorouracil (5-Fu) transporter was designed based on the use of two new biocompatible gold nanosystems: (i) a gold nanoparticle precursor, Au@16-Ph-16, stabilized with the positively charged gemini surfactant 16-Ph-16, and (ii) the compacted nanocomplexes formed by the precursor and DNA/5-Fu complexes, Au@16-Ph-16/DNA–5-Fu. The physicochemical properties of the obtained nanosystems were studied by using UV–visible spectroscopy, TEM, dynamic light scattering, and zeta potential techniques. Method tuning also requires the use of circular dichroism, atomic force microscopy, and fluorescence spectroscopy techniques for the prior selection of the optimal relative Au@16-Ph-16 and DNA concentrations (R = CAu@16-Ph-16/CDNA), biopolymer compaction/decompaction, and 5-Fu release from the DNA/5-Fu complex. TEM experiments revealed the effective internalization of the both precursor and Au@16-Ph-16/DNA–5-Fu-compacted nanosystems into the cells. Moreover, cytotoxicity assays and internalization experiments using TEM and confocal microscopy showed that the new strategy for 5-Fu administration enhanced efficacy, biocompatibility and selectivity against lung cancer cells. The differential uptake among different formulations is discussed in terms of the physicochemical properties of the nanosystems.

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

“…Therefore, the results obtained with TEM studies on C I and N I samples showed that small size spherical nanoparticles usually enter and exit the cell more efficiently [ 16 , 90 ]. Thus, the high degree of internalization obtained for the nanosystems used was in line with previous research on the cellular uptake of different nanoparticles [ 38 ]. The effects of these nanosystems on the cells are reflected in the data presented on cell viability, where they are enhanced for the smaller C 1 and C 1 + N 1 ( Figure 14 ).…”

“…To study the internalization of the different treatments, a transmission ele microscopy study was carried out. For this study, cells were fixed after a 24 h treat to ensure that the nanosystems had entered the cells [38]. The study was carried ou Au@16-Ph-16 (N3), Au@16-Ph-16/DNA/Doxo (C3) and Au@16-Ph-16/DNA/Doxo + A To study the internalization of the different treatments, a transmission electron microscopy study was carried out.…”

“…The study was carried ou Au@16-Ph-16 (N3), Au@16-Ph-16/DNA/Doxo (C3) and Au@16-Ph-16/DNA/Doxo + A To study the internalization of the different treatments, a transmission electron microscopy study was carried out. For this study, cells were fixed after a 24 h treatment, to ensure that the nanosystems had entered the cells [38]. The study was carried out with Au@16-Ph-16 (N 3 ), Au@16-Ph-16/DNA/Doxo (C 3 ) and Au@16-Ph-16/DNA/Doxo + Au@16-Ph-16 (C 3 + N 3 ) at 24 h, compared to the control without treatments in non-tumorigenic prostate PNT2 cells (Figure 9), considering control cells, prostate tumor-derived LNCaP cells sensitive to hormone therapy (Figure 10) and DU145 tumor cells derived from prostate tumor, a model of prostate cancer resistant to castration and not responsive to hormonal therapy (Figure 11).…”

“…Other similar strategies that employ DNA as a biopolymer used Doxo-loaded DNA nanoparticles for the treatment of ovarian cancer, where results from immunohistochemical analysis demonstrated low number of proliferative cells in the ovarian tumor tissue [ 36 ]. As can be demonstrated, the coating of the system with a biopolymer such as DNA leads to an improvement in the drugs’ biocompatibility, providing colloidal stability and improving the systemic circulation time [ 37 , 38 , 39 , 40 ].…”

“…Second, the appropriate Au@16-Ph-16/DNA molar ratios for inducing both DNA–Doxo compaction/decompaction processes were explored. To do this, different spectroscopic, structural and characterization techniques were employed, adapting the experience acquired in previous studies to the new nanocomplexes [ 38 ]. Once the optimal working conditions were established, we proceeded to study both the cell viability and the internalization of the compacted complexes Au@16-Ph-16/DNA–Doxo (C I ) in different prostate and liver cell lines, as well as the effect that the addition of nanoparticles at the appropriate concentration (N I ) had on the decompaction and the release of the drug inside the cell.…”