Effect of TAT-DOX-PEG irradiated gold nanoparticles conjugates on human osteosarcoma cells

Abstract

The paper aims to investigate the cytotoxic effect on tumor cells of irradiated AuNPs in green light and subsequently functionalized with HS-PEG-NH 2. The toxicity level of gold conjugates after their functionalization with DOX and TAT peptide was also evaluated. The AuNPs were prepared using the modified Turkevich method and exposed to visible light at a wavelength of 520 nm prior their PEGylation. The optical properties were analyzed by UV-vis spectroscopy, the surface modification was investigated using FTIR and XPS spectroscopies and their sizes and morphologies were evaluated by TEM and DLS techniques. DOX and TAT peptide were linked to the surface of PEGylated AuNPs by reacting their amino groups with glycidyloxypropyl of PEGylated DOX or TAT conjugates under mild conditions at room temperature and in the presence of ethanol as catalyst. The conjugates containing DOX or DOX and TAT have been characterized by fluorescence and FTIR techniques. The changes of electrochemical features were observed using cyclic voltammetry, suggesting a better stability of irradiated nanoparticles. By mass spectrometry it was confirmed that the compounds of interest were obtained. The cell viability test showed that irradiated and non-irradiated nanoparticles coated with PEG are not toxic in normal cells. Tumor cell viability analysis showed that the PEGylated nanoparticles modified with DOX and TAT peptide were more effective than pristine DOX, indicating cytotoxicity up to 10% higher than non-irradiated ones. The presence of gold nanomaterials (AuNPs) in biomedicine and particularly in antitumor therapy still remains a topic of wide debate, as evidenced by the tremendous amount of scientific works on this issue in recent years 1-3. An impressive number of research studies have straightened their efforts toward the use of AuNPs in enhancing the efficiency of cancer treatment, due to their ease production and chemical functionalization of their surface 4,5. Gold nanoparticles are feasible to be developed as versatile nontoxic carriers for drug release as long as they are able to be conjugated with different molecules, including chemotherapeutics, antibodies, peptides, ligands, and other structures which are likely to promote a great capacity to penetrate the tumor site, resulting in a predominant accumulation of bioactive agent in the tumor region 6,7. On the other hand, the passive anticancer effect based on the accumulation strategy of AuNPs at the tumor site is limited by the inherent heterogeneities of tumor vasculature 8. It was shown that nanoparticle concentration in the target tissue is influenced by renal clearance rate, and also by activation of immune system mechanisms such as opsonization or nonspecific particle phagocytosis, fulfilled by the reticuloendothelial system (RES).

Targeted Photodynamic Therapy Using Alloyed Nanoparticle-Conjugated 5-Aminolevulinic Acid for Breast Cancer

“…Au–Ag NPs with the approximate size of 16.4 ± 3.9 nm with long-term stability were obtained. The high stability of the synthesized bimetallic citrate Au–Ag NPs was due to the presence of sodium citrate, which induces an abundance of negative charges, creating repulsions between NPs and so no aggregation was observed [ 39 ]. This finding was confirmed by UV-Visible spectroscopy and the reported polydispersity indexes (PDIs).…”

“…The primary amine group of the PEG is also represented with a characteristic band in the spectra of all PEGylated compounds at 3100–3200 cm −1 . Moreover, the peak at 400–750 cm −1 can be related to the bonding of Au–Ag NPs with sulfur (Au–Ag-S) [ 39 ]. The 1725 cm −1 band can be associated with the stretching absorption of the C=O groups, which are present in the spectra of all NCs, confirming the attachment of 5-ALA.…”

Smart Therapeutic Strategy of pH‐Responsive Gold Nanoparticles for Combating Multidrug Resistance

“…The major characteristic bands in the FTIR spectrum were found at 3417 cm −1 indicates the presence of OH stretching, the vibration peak at around 2949 cm −1 for CH stretching, various bands from 3600 to 2800 cm −1 are the characteristic for OH, NH, and CH stretching vibrations. [ 34 ] The stretching vibration bond at 1654, 1587, and 1392 cm −1 with a slight shift in wave numbers represents the CO, amide I, amide II, and amide III, CC stretching, respectively. More precisely concerning the few more stretching peaks between the 1700 and 1000 cm −1 are associated with the quinine and ketone groups of the DOX.…”

An Overview of the Importance of Transition-Metal Nanoparticles in Cancer Research

“…Covalent binding of doxorubicin is another reason for such beneficial results of Au-TAT-DOX-PEG NPs ( Figure 2 A). An efficacy equivalent to the cytotoxic effect of pure doxorubicin on the human osteosarcoma (HOS) cell line was reported with only 3% of the substance attached to the nanoparticle [ 16 ].…”