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Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

ABSTRACT: Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers as targeted drug delivery vehicles, because they can be guided to their target with the help of an external magnetic field. Functionalization of nanoparticles' surface with molecules, which bind with high affinity to receptors on target tissue significantly facilitates delivery of coated nanoparticles to their targeted site. Here, we demonstrate conjugation of an antiangiogenic and antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA). Successful conjugation was confirmed by various analytical techniques (FTIR, SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines (HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells that were exposed to either the nanoparticles modified with sebacic acid or A7R peptide solely, what might be partially caused by a process of internalization.

SUBMITTER: Niescioruk A

PROVIDER: S-EPMC5406482 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

Niescioruk Anna A Nieciecka Dorota D Puszko Anna K AK Królikowska Agata A Kosson Piotr P Perret Gerard Y GY Krysinski Pawel P Misicka Aleksandra A

Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology 20170426 5

Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers as targeted drug delivery vehicles, because they can be guided to their target with the help of an external magnetic field. Functionalization of nanoparticles' surface with molecules, which bind with high affinity to receptors on target tissue significantly facilitates delivery of coated nanoparticles to their targeted site. Here, we demonstrate conjugation of an antiangiogenic and antitumor peptide ATWLPPR (A7R) to ...[more]

PMID: 28503085

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Project description:Combination therapy remains one of the most promising and intensively developed direction in cancer treatment. This study is aimed to combine and investigate the anticancer properties of silver nanoparticles (NPs) and Amanita muscaria mushroom in gel formulation. For this, hyaluronic acid was used as gel-forming agent, whereas Amanita muscaria extract was used as capping agent during silver and ultrasmall iron oxide (MAg) NPs synthesis. Amanita muscaria compounds formed NP's surface layer and contributed anticancer properties, whereas silver NPs contributed anticancer, fluorescence and photoactive properties to the gel. Physicochemical characterization included X-ray diffraction (XRD), microscopies (SEM, cryo-SEM, TEM, confocal fluorescence), spectrofluorometric method, thermogravimetric analysis (TGA), dynamic light scattering (DLS) techniques, energy dispersive (EDS), Fourier transform infrared (FTIR) and ultraviolet-visible (UV-Vis) spectroscopies, zeta-potential and rheological measurements. Microstructure analysis of hyaluronic acid/MAg NPs gel was performed by cryo-SEM technique. We showed that hyaluronic acid is a perfect gel-forming agent from both biomedical and technological points of view. It is well-mixed with MAg NPs forming stable gel formulation; high homogeneity of hyaluronic acid/MAg NPs gel was shown by SEM EDS elemental mapping. Microstructure of the gel was found to be highly ordered and consisted of domains from perforated parallel tubular structures. This finding expanded our understanding of gels and broke the stereotype of gel structure as chaotic network of fibers. Cytotoxicity studies performed on 2D and 3D HeLa cell cultures pointed to a high potential of hyaluronic acid/MAg NPs gel for local treatment of cancer. Cell response was found to be significantly different for 2D and 3D cell cultures that was related to their different cytoarhitecture and gene expression. Thus, the results of the cellular spheroids viability showed that they were significantly more resistant to the cytotoxic action of MAg NPs and their gel formulation than 2D cell culture. Hyaluronic acid used as gelling agent in gel formulation was found to increase an effectiveness of active components (MAg NPs, Amanita muscaria extract) probably improving their transport inside HeLa spheroids.

Project description:Exposures to high doses of manganese (Mn) via inhalation, dermal contact or direct consumption can cause adverse health effects. Welding fumes are a major source of manganese containing nanoparticles in occupational settings. Understanding the physicochemical properties of manganese-containing nanoparticles can be a first step in understanding their toxic potential following exposure. In particular, here we compare the size, morphology and Mn oxidation states of Mn oxide nanoparticles generated in the laboratory by arc discharge to those from welding collected in heavy vehicle manufacturing. Fresh nanoparticles collected at the exit of the spark discharge generation chamber consisted of individual or small aggregates of primary particles. These nanoparticles were allowed to age in a chamber to form chain-like aggregates of primary particles with morphologies very similar to welding fumes. The primary particles were a mixture of hausmannite (Mn3O4), bixbyite (Mn2O3) and manganosite (MnO) phases, whereas aged samples revealed a more amorphous structure. Both Mn2+ and Mn3+, as in double valence stoichiometry present in Mn3O4, and Mn3+, as in Mn2O3 and MnOOH, were detected by X-ray photoelectron spectroscopy on the surface of the nanoparticles in the laboratory nanoparticles and welding fumes. Dissolution studies conducted for these two Mn samples (aged and fresh fume) reveal different release kinetics of Mn ions in artificial lysosomal fluid (pH 4.5) and very limited dissolution in Gamble's solution (pH 7.4). Taken together, these data suggest several important considerations for understanding the health effects of welding fumes. First, the method of particle generation affects the crystallinity and phase of the oxide. Second, welding fumes consist of multiple oxidation states whether they are amorphous or crystalline or occur as isolated nanoparticles or agglomerates. Third, although the dissolution behavior depends on conditions used for nanoparticle generation, the dissolution of Mn oxide nanoparticles in the lysosome may promote Mn ions translocation into various organs causing toxic effects.

Dataset Information

Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

Publications

Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

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