ABSTRACT
The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.
Subject(s)
Antineoplastic Agents/chemical synthesis , Breast Neoplasms/metabolism , Oxazines/chemical synthesis , Photosensitizing Agents/chemical synthesis , Reactive Oxygen Species/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Female , Humans , Mice , Molecular Structure , NIH 3T3 Cells , Oxazines/chemistry , Oxazines/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacologyABSTRACT
Morphometric characterization of nanoparticles is crucial to determine their biological effects and to obtain a formulation pattern. Determining the best technique requires knowledge of the particles being analyzed, the intended application of the particles, and the limitations of the techniques being considered. The aim of this article was to present transmission (TEM) and scanning (SEM) electron microscopy protocols for the analysis of two different nanostructures, namely polymeric nanoemulsion and poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and to compare these results with conventional dynamic light scattering (DLS) measurements. The mean hydrodynamic diameter, the polydispersity index, and zeta potential of the nanostructures of polymeric nanoemulsion were 370.5 ± 0.8 nm, 0.133 ± 0.01, and -36.1 ± 0.15 mV, respectively, and for PLGA nanoparticles were 246.79 ± 5.03 nm, 0.096 ± 0.025, and -4.94 ± 0.86 mV, respectively. TEM analysis of polymeric nanoemulsion revealed a mean diameter of 374 ± 117 nm. SEM analysis showed a mean diameter of 368 ± 69 nm prior to gold coating and 448 ± 70 nm after gold coating. PLGA nanoparticles had a diameter of 131 ± 41.18 nm in TEM and 193 ± 101 nm in SEM. Morphologically, in TEM analysis, the polymeric nanoemulsions were spherical, with variable electron density, very few showing an electron-dense core and others an electron-dense surface. PLGA nanoparticles were round, with an electron-lucent core and electron-dense surface. In SEM, polymeric nanoemulsions were also spherical with a rough surface, and PLGA nanoparticles were round with a smooth surface. The results show that the "gold standards" for morphometric characterization of polymeric nanoemulsion and PLGA nanoparticles were, respectively, SEM without gold coating and TEM with negative staining.
Subject(s)
Lactic Acid/chemistry , Nanoparticles/ultrastructure , Polyglycolic Acid/chemistry , Hydrodynamics , Nanoparticles/chemistry , Particle Size , Polylactic Acid-Polyglycolic Acid CopolymerABSTRACT
The use of magnetic nanoparticles (MNPs) in drug delivery vehicles must address issues such as drugloading capacity, desired release profile, aqueous dispersion stability, biocompatibility with cells and tissue, and retention of magnetic properties after interaction with macromolecules or modification via chemical reactions. Amphotericin B (AmB) is still the first choice for the treatment of severe paracoccidioidomycosis, an important systemic fungal infection caused by Paracoccidoides brasiliensis. Unfortunately, AmB causes acute side effects (mainly urinary problems) following intravenous administration, which limits its clinical use. The use of magnetic nanoparticles stabilized with biocompatible substances, together with the possibility of their conjugation with drugs has become a new nanotechnological strategy in the treatment of diseases for drug delivery to specific locations, such as the lungs in paracoccidoidiodomycosis. This review provides an overview of the disease, its etiologic agent and treatment with emphasis on the main strategies to improve the use of AmB in nanoformulations.
El uso de nanopartículas magnéticas (MNPS) en los vehículos de suministro de fármacos debe abordar cuestiones como la capacidad de carga de las drogas, el perfil deseado de liberación, estabilidad de la dispersión acuosa, biocompatibilidad con las células, tejidos y la conservación o la modificación de las propiedades magnéticas después de la interacción con macromoléculas y/o reacciones químicas. La anfotericina B (AnB) continua siendo la primera opción para el tratamiento de la paracoccidioidomicosis grave, una importante infección sistémica causada por el hongo Paracoccidioides brasiliensis. Sin embargo, la AnB causa efectos secundarios agudos (principalmente problemas urinarios) tras la administración intravenosa, limitando su uso clínico. El uso de nanopartículas magnéticas estabilizadas con sustancias biocompatibles y conjugadas con fármacos, se ha convertido en una nueva estrategia nanotecnológica para el tratamiento de enfermedades en sitios específicos, como los pulmones en paracoccidoidiodomycosis. En esta revisión se hace una descripción general de la enfermedad, su agente etiológico y su tratamiento con énfasis en la principales estrategias para mejorar el uso de AnB en nanoformulaciones.
