Induction of Immunogenic Cell Death by Photodynamic Therapy Mediated by Aluminum-Phthalocyanine in Nanoemulsion.

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs-CRT, HSP70, HSP90, HMGB1, and IL-1ß-were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.

Low urinary selenium levels are associated with iodine deficiency in Brazilian schoolchildren and adolescents.

BACKGROUND: Selenium (Se) and iodine (Io) are important micronutrients for the proper functioning of the thyroid gland, as they are crucial for the synthesis and activation of the thyroid hormones (TH) triiodothyronine (T3) and thyroxine (T4). OBJECTIVE: To evaluate the Se and Io nutritional status among schoolchildren. METHODOLOGY: Cross-sectional, descriptive and analytical study conducted in 982 schoolchildren aged 6-14 years from public schools in the state of Bahia, Brazil. Sociodemographic and anthropometric variables, as well as urinary Se (USC) and Io concentrations (UIC) using the inductively coupled plasma mass spectrometry (ICP-MS) method and thyroid-stimulating hormone (TSH) from filter paper blood collection, were evaluated. RESULTS: The median USC and UIC were 38.7 and 210.0 (IQR: 26.8-52.9 and 129.3-334.1 µg/L, respectively). The prevalence of iodine deficiency and excessive UIC were observed in 17.1% and 30.9% of schoolchildren, respectively. Concomitant low USC and IoD was found in 3.9% of schoolchildren. There was a positive correlation between USC and UIC (r = 0.60; p = 0.00). The median TSH was 0.95 (IQR: 0.69-1.30 µUI/L). CONCLUSIONS: This study demonstrates that USC is a good biomarker for assessing Se status, meantime more studies are needed to establish cutoff USC in child population. Despite adequate median intake, a subgroup of schoolchildren had IoD and low USC. The correlation between UIC and USC point at the importance of two micronutrients, raising the question whether measuring Se should be included in monitoring programs that address the prevention of nutritional disturbances.

A xanthene derivative, free or associated to nanoparticles, as a new potential agent for anticancer photodynamic therapy.

The efficacy and safety of photodynamic therapy (PDT) have drawn much attention from clinicians and researchers in the field of anticancer treatments since the last century. Despite the numerous positive outcomes, the works on PDT have brought to light over the last decades, much room remains for improvements in PDT tools, mainly on the photosensitizer molecules. This work reports the first experiments evidencing the photosensitizing activity of DHX-1, a xanthene derivative-based near-infrared probe recently described in the literature, both as a free molecule and associated to a nanostructured lipid carrier. The results show that the DHX-1 presents a broad band of light absorption within the optical window of biological tissues (600-800 nm), generates reactive oxygen species when photoactivated, and is phototoxic against murine breast adenocarcinoma 4T1 cells and murine fibroblast NIH-3T3 in vitro. Moreover, the association of DHX-1 to a nanostructured lipid carrier strongly reduced its phototoxicity against the normal cell line.