Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Aim This study aimed to systematically review existing literature regarding the association between dental procedures—such as tooth extractions and periodontal therapy—and occurrence of medication-related osteonecrosis of the jaw (MRONJ) in individuals using bone-modifying drugs. Methods Search strategies were performed in PubMed, Scopus, Web of Science and Cochrane Library for a timeframe ending in December 2021. Study selection, data extraction and risk of bias were analyzed independently by two researchers. Three meta-analyses were performed, estimating the crude risk ratio (RR), the adjusted odds ratio (OR) and the adjusted hazard ratio (HR) for the association between tooth extraction and MRONJ. Results Of the 1,654 studies initially retrieved, 17 were ultimately included. The majority of patients with MRONJ in these studies were female, with a mean age of 64 years. Zoledronic acid was the most commonly used drug among patients with MRONJ, and cancer was the most frequent underlying health condition. Regarding the performed meta-analyses, crude and adjusted analyses demonstrated that tooth extraction increased the risk for MRONJ by 4.28 (95% confidence interval [95%CI]: 1.73–10.58), the OR for MRONJ by 26.94 (95%CI: 4.17–174.17), and the HR for MRONJ by 9.96 (95%CI: 4.04–24.55). Conclusion It was concluded that performing dental procedures, especially tooth extraction, in patients using bone-modifying drugs increased the risk of MRONJ occurrence and, therefore, should be avoided. Further studies, using adjusted data, are warranted.

Electrospinning is a strand of nanoscience for the production of fibers in nano and micrometric scales and when combined with other techniques it becomes a powerful tool for application in various branches of science. A promising combination of electrospinning is photodynamic therapy (PDT) and photodynamic inactivation of microorganisms (PDI) for the manufacture of fibers with photoactive characteristics that can be used with great ease in the medical field. This systematic review reports technical information, preparation and characterization of nano and microfibers obtained by the electrospinning technique with applicability in PDT/PDI.

Sol-gel synthesis is commonly used to modify the surface of mesoporous silica nanoparticles (MSN) with organic groups through the co-condensation method. The template removal, and the site-controlled addition of organic groups and their partial occlusion inside the framework walls are still a challenge in the one-pot synthesis. Here, we optimize the synthesis of amino-modified MSN by the combination of efficient template removal methodology with the precise time of the amino precursor addition to achieve superb mesoporous material. The addition after the growth process produces a sample with a significantly higher amount of NH2 on the external surface when compared to the standard procedure. The template removal by reflux with isopropanol/H+ eliminated ca. 90% of cetyltrimethylammonium bromide (CTAB), and preserved the mechanical and thermal properties, even with thin walls (2.1 nm). The synthesized nanoparticles possess stability, appropriate size, and a positive surface. This makes them excellent nanocarriers, especially in the biomedical field.

This work presents an equation concerning effective light doses (Dabs; J cm-2) absorbed by photosensitizer molecules that are involved directly in photochemical and photodynamic processes. These molecules are photostimulated by different polychromatic LED sources with distinct photonic properties. The inherent photosensitizer photobleaching process, source irradiation emission spectrum (wavelength range), light source power, irradiation time, and LED-methylene blue spectral overlap degree were the relevant parameters considered for Dabs. This was performed with an experimental system comprised of methylene blue and its photosensitization ability on substrate DFBF (1,3-diphenylisobenzofuran) photodegradation, starting from different polychromatic LED sources. We demonstrated that such factors significantly affect photosensitizer light absorption, thus influencing the efficiency of a specific photochemical process. This occurs due to the selection of non-optimal experimental conditions associated with less precision from photonic source measurements, and therefore, less control on the actual Dabs. Such insights are interestingly absent in various studies with regards to a plethora of systems.

A simple and low cost experiment is proposed to chemistry students associating the Photodynamic Activity involving Chemical and Biochemical concepts. The inclusion of this experiment in undergraduate courses in Chemistry promotes interdisciplinarity and contextualization, combining current and relevant topics to the teaching of program content. The experiment used the Methylene Blue and Erythrosine B as dyes to demonstrate the photodynamic action of these photosensitizers in the inhibition of microbial growth. Both dyes presented satisfactory results against environmental microorganisms. The growth inhibition was caused exclusively by the photochemical processes undergone by the dye/light/oxygen, with LED light exposure.

The correct selection of a dye that has effective action as a photosensitizer is a primary concern for successful therapeutic outcomes. The effectiveness of the photodynamic agent is related to both the targeting of cell membranes and the photochemical yield of the chosen dye. The distributions of xanthene derivatives Eosin Y, Erythrosin B, and Rose Bengal B in vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in both liquid-crystalline and gel phases were investigated by fluorescence spectroscopy. Binding constants, fluorescence anisotropy, fluorescence quenching, fluorescence quantum yield, and fluorescence resonance energy transfer at physiological pH conditions were determined. To Erythrosin B and Eosin Y, the iodide quenching rate constant was shown to involve a sphere of action mechanism driven by a specific interaction between Erythrosin B and Eosin Y molecules and the choline head-group of the phospholipid; in contrast, Rose Bengal B was located deep in the membrane and this mechanism was not present. The dyes can be ordered by their penetration depth in the membrane, and this order was found to be Eosin Y < Erythrosin B < Rose Bengal B. These results demonstrate a rational approach for the screening of more active agents for photodynamic therapy based on the affinity between the xanthene derivatives and DPPC vesicles.

<p>Aluminum phthalocyanine chloride (AlPcCl) is a photoactive compound which has been used as a photosensitizer (PS) in photodynamic therapy (PDT). Its spectroscopic properties have been studied in solvents of different polarities (ethanol, acetone, dimethylsulfoxide and chloroform). Its solubility has been found to decrease with increasing solvent polarity, together with full self-aggregation in aqueous solution. The binding of AlPcCl to the copolymer Pluronic^TM micellar class P-123 and F-127 used as solubilizer/carriers was studied. Greater interaction between the more hydrophobic copolymer P-123 and AlPcCl was observed, besides a complex interaction profile involving different AlPcCl forms (self-aggregate/monomeric form) in the copolymers. Time- and temperature-dependent structural organization of AlPcCl in the copolymers was also observed. Thus, AlPcCl has a strong tendency to self-aggregate with increasing solvent polarity, an effect also observed in micellar media.</p>

Ftalocianinas (Pc) são compostos sintéticos de interesse em diversas áreas. Contudo, sua elevada hidrofobicidade favorece o indesejável processo de agregação em meio aquoso. Estudos realizados com a Pc de hidroxi-alumínio (AlPcOH) em diferentes misturas água/etanol (v/v) mostraram que esta encontra-se na forma monomérica em proporções de água inferiores a 30%. Em 40 e 50% água/etanol tem-se a formação de dímeros unidos por ligação hidrogênio ou em ponte Al-O-Al, enquanto que em porcentagens de água superiores a 60% o processo de agregação é complexo, envolvendo múltiplos equilíbrios e agregados de tamanhos grandes (tipo J).

Phthalocyanines (Pc) are synthetic compounds of interest in various fields. However, their high hydrophobicity promotes the undesirable aggregation process in aqueous media. Studies carried out with aluminum phthalocyanine hydroxide (AlPcOH) in different water/ethanol mixtures (v/v) have shown that in proportions of water lower than 30% the Pc is in the monomeric form. At 40 and 50% water/ethanol there was formation of dimers linked by hydrogen bonding or Al-O-Al bridged, while in percentages of water higher than 60% the aggregation process is complex, with multiple equilibria and higher-order aggregates (J-type).

An experiment was proposed applying the Chemometric approach of Multivariate Analysis for inclusion in undergraduate Chemistry courses to promote and expand the use of this analytical-statistical tool. The experiment entails the determination of the acid dissociation constant of dyes via UV-Vis electronic spectrophotometry. The dyes used show from simple equilibrium to very complex systems involving up to four protolytic species with high spectral overlap. The Chemometric methodology was more efficient than univariate methods. For use in classes, it is up to the teacher to decide which systems should be utilized given the time constraints and laboratory conditions.

In this work, the spectroscopic properties of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMPP) in solvents of different polarities and water/ethanol mixtures were studied by electronic absorption spectroscopy and resonance light scattering associated with statistical analysis. The molar absorption coefficient and emission maximum of TMPP were dependent on solvent polarity. In the water/ethanol mixture, TMPP remained monomeric up to 25% of water, when it reaches its critical aggregation percentage. Oblique head-to-tail aggregate was found at intermediate water content (35 - 55%), while formation of a J-type aggregate was observed at higher water content (> 60%).

The physicochemical properties (solubilization, structural organization and stability) of meso-tetrakis(p-methoxyphenyl)porphyrin (TMPP), a promising photosensitizer for photodynamic therapy, solubilized in polymeric micelles of tri-block copolymers PluronicTM P-123 and F-127, were studied. The formulations obtained by the solid dispersion method led to monomerization of TMPP in these copolymers. Solubility studies showed that P-123 solubilizes double the photosensitizer than F-127. The self-aggregation phenomenon was affected by the [TMPP]/[poloxamer] ratio and medium temperature. The decrease in the temperature of these systems promoted the formation of different kinds of TMPP aggregates intrinsically connected with the structural changes occurring in the micelles.

O desenvolvimento de fármacos para terapia foto-dinâmica (TFD) é uma importante área de pesquisa devido ao seu crescente uso em aplicações médicas. Portanto, é importante desenvolver novos métodos de bioensaios para TFD fotossensibilizadores que sejam de baixo custo, de fácil execução e altamente sensíveis às condições do meio. Corantes xantênicos (fluoresceína, rosa de bengala B, eritrosina B e eosina Y) iluminados com luz LED foram investigados usando Artêmia salina como bioindicador da atividade fotodinâmica. Neste estudo, três fatores foram investigados (i) concentração do fotossensibilizador; (ii) o tempo de irradiação LED e (iii) o tempo de espera entre a adição do fotossensibilizador e o início da irradiação. Para analisar a foto-mortandade da A. salina foi aplicado o planejamento fatorial 23 completo. A morte da A. salinafoi relacionada à estrutura do corante e à interação entre o tempo de irradiação e a concentração do fotossensibilizador. Cerca de 60% da morte do crustáceo foi obtida usando rosa de bengala B, que apresenta o maior rendimento quântico de oxigênio singlete devido aos átomos de iodo substituintes no anel xantênico. O bioensaio proposto usando A. salina, corantes xantenos e irradiação LED foi apropriado para a avaliação quantitativa de fármacos para TFD.

The development of drugs for photodynamic therapy (PDT) is an important area of research due to their growing use in medical applications. Therefore, it is important to develop new bioassay methods for PDT photosensitizers that are inexpensive, easy to handle and highly sensitive to environmental conditions. Xanthene dyes (fluorescein, rose bengal B, erythrosine B and eosin Y) with LED light sources were investigated using Artemia salina as a bioindicator of photodynamic activity. In this study, three factors were investigated: (i) photosensitizers concentration, (ii) the LED irradiation time and (iii) the waiting time between the addition of the photosensitizers and the beginning of the irradiation. To analyze the photo-killing of A. salina, it was employed a 23 full factorial design. The death of A. salina was related to dye structure and the interaction between the irradiation time and the photosensitizers concentration. About 60% of crustaceans death was obtained using rose bengal B, which presentes the highest quantum yield of singlet oxygen due to the number of iodide substituents in the xanthenes ring. The proposed bioassay using A. salina, xanthene dyes and LED irradiation was found suitable for quantitative PDT drug evaluation.

The self-aggregation of pheophytin, a possible photosensitizer for Photodynamic Therapy, is solved by formulation in polymeric surfactant as P-123. The photosensitizer incorporation was found to be time dependent, exhibiting two steps: a partition at the micellar interface followed by an incorporation into the micelle core. The photodynamic efficiency of the formulation was tested by the bioassays against Artemia salina. In order to evaluate how the experimental parameters: pheophytin concentration, P-123 percentage and illumination time influenced the death of artemia, the factorial design 2³ was chosen. The illumination time was found to be the main factor contributing to the mortality of artemia.

O espectro de absorção de DPH, em concentração fixa, não varia com o teor de água em solvente orgânico. Tem-se a banda de monômeros igual àquela em etanol puro. A absorção não muda até o limite de 54 e 46% de água em etanol e DMSO, respectivamente, para [DPH] = 5,0 × 10-6 mol L-1 a 30 °C. Entretanto, em misturas com água muito abaixo desses conteúdos críticos, observou-se um decaimento intenso de fluorescência enquanto a absorção manteve-se constante. Propõe-se que moléculas de água atuam como supressores dos estados excitados e a constante de supressão de Stern-Volmer através de intensidade relativas, resultou em 7,4 × 10-2 (água/etanol) e 2,6 × 10-2 L mol-1 (água/DMSO). Os tempos de vida do DPH na ausência e presença do supressor forneceram constantes de 7,1 × 10-2 L mol-1 em água/etanol, indicando supressão dinâmica. Em investigações de ambientes com esta sonda, este processo deve ser considerado tendo em vista o risco de erros de interpretação.

The absorption spectra of DPH at fixed concentration do not change with water content in organic solvents. It exhibits monomer bands, such as those obtained in ethanol. The absorption did not change for solutions up to 54 and 46% of water in ethanol and DMSO, respectively, for [DPH] = 5.0 × 10-6 mol L-1 at 30 °C. However, at the same experimental conditions, a gradual sharp decay of the DPH fluorescence is observed. It is proposed that water molecules below these water concentration limits act as quenchers of the excited states of DPH. Stern-Volmer quenching constants by intensities measurements are 7.4 × 10-2 (water/ethanol) and 2.6 × 10-2 L mol-1 (water/DMSO). DPH lifetime measurements in the absence and presence of water resulted in 7.1 × 10-2 L mol-1 in water/ethanol, which pointed out that the process is a dynamic quenching by water molecules. For experiments using DPH as probe, this process can affect data, leading to misunderstanding interpretation.