Aminolevulinic acid with gold nanoparticles: a novel theranostic agent for atherosclerosis.

In this study, 5-aminolevulinic acid (ALA) gold nanoparticles (ALA:AuNPs) functionalized with polyethylene glycol (PEG) were synthesized and administered to rabbits to evaluate their use in clinical practice as theranostic agents for atherosclerosis. This was done by measuring the porphyrin fluorescence extracted from the rabbits' blood and feces. An increase in blood and feces porphyrin emission after ALA:AuNP administration suggests that ALA was incorporated by gold nanoparticles, its structure was preserved, and a rapid conversion into endogenous porphyrins occurred, overloading the synthetic pathway that led to protoporphyrin IX (PPIX) accumulation. This finding indicated that this method can aid in the early diagnosis and therapy of atherosclerosis with high sensitivity.

Study of the interactions of gold nanoparticles functionalized with aminolevulinic acid in membrane models.

Gold nanoparticles have been intensively studied in cancer therapy to improve drug release, increasing therapeutic action and reducing adverse effects. The interaction between gold nanoparticles and cell membranes can give information about the cell internalization. In this study, gold nanoparticles with aminolevulinic acid (5-ALA) were synthesized using the photoreduction method (5-ALA: AuNPs). The prodrug 5-ALA is responsible for protoporphyrin IX synthesis inside the cell and allows the use of therapies as photodynamic and sonodynamic therapies. The cytotoxicity test was performed on a breast cancer tumor line (MCF-7), and high Content Screening assay was applied to evaluate the entry of nanoparticles into cells. DPPS Langmuir monolayers were assembled at the air/water interface and employed as a simplified membrane model for half of a tumorigenic cell membrane. We assessed the molecular interactions between 5-ALA: AuNPs and phospholipids using tensiometry (π-A isotherms) and vibrational spectroscopy (PM-IRRAS) experiments. We found that the functionalized gold nanoparticles strongly interact with DPPS polar head groups (especially phosphate and carbonyl), changing the phospholipid hydration and leading to a general decrease in the monolayer conformational order. This work then probes that specific interaction between 5-ALA: AuNPs and the negatively charged phospholipid can be assessed using Langmuir monolayers as simplified biomembrane models.

Uptake of silver, gold, and hybrids silver-iron, gold-iron and silver-gold aminolevulinic acid nanoparticles by MCF-7 breast cancer cells.

BACKGROUND: Nanoparticles show promise for theranostic applications in cancer. The metal-based nanoparticles can be used both as photosensitizers and delivery vehicles. In bimetallic particles based on gold or silver and iron, a combination of the plasmonic features of the gold or silver components with the magnetic properties of the iron makes these hybrid nanomaterials suitable for both imaging and therapeutic applications. Herein, we discuss toxicity and cell internalization of metallic (silver and gold) and bimetallic (silver-iron, gold-iron, and silver-gold) aminolevulinic acid (ALA) nanoparticles. ALA can control the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), commonly used in photodynamic therapy. METHODS: Nanoparticles were synthesized by photoreduction method and characterized by UV/Vis spectra, Zeta potential, FTIR, XRD, and transmission electron microscopy. The amount of singlet oxygen generation by a yellow LED, and ultrasound was studied for gold, gold-iron, and silver-gold nanoparticles. Cytotoxicity assays of MCF-7 in the presence of nanoparticles were performed, and PpIX fluorescence was quantified by high content screening (HCS). RESULTS: Red fluorescence observed after 24 h of nanoparticles incubation on MCF-7 cells, indicated that the ALA in surface of nanoparticles was efficiently converted to PpIX. The best results for singlet oxygen generation with LED or ultrasound irradiation were obtained with ALA:AgAuNPs. CONCLUSIONS: The studied nanoparticles present the potential to deliver aminolevulinic acid to breast cancer cells efficiently, generate singlet oxygen, and convert ALA into PpIX inside the cells allowing photodiagnosis and therapies such as photodynamic and sonodynamic therapies.