Editorial: Antimicrobial Photodynamic Therapy: A New Paradigm in the Fight Against Infections

According to a 2019 report from the Center for Disease Control and Prevention (CDC), more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35, 000 people die as a result. This special issue is focused on Antimicrobial Photodynamic Therapy (PDT), which is a new strategy to fight against infections. PDT is mostly used in the treatment of cancer, and non-melanoma skin cancer is the most widely recognized indication. A photosensitizer that is activated by visible light in the presence of oxygen can generate reactive oxygen species resulting in the death of the microorganisms, without damaging the surrounding tissue. This innovative way of destroying microbial pathogens has many advantages compared with the conventional antimicrobials and antibiotics used so far. It has a broad spectrum of action, being able to kill or inactivate bacteria, fungi, viruses and protozoa..

La naturaleza como experimento constructivo. El Pabellón de Japón para la XI Bienal de Venecia (Junya Ishigami, 2008)

El trabajo de Junya Ishigami ha sido objeto de estudio frecuente en el marco de una arquitectura próxima a la naturaleza, interés compartido por la constelación de arquitectos japoneses de finales del siglo XX y principios del XXI. Este artículo estudia la obra de Ishigami de manera más específica en torno a la condición natural como laboratorio de construcción, acorde a una doble finalidad con piezas destinadas a exponerse en galerías o a formalizarse como arquitectura. Esta dedicación paralela permite discutir la operatividad de unas estrategias enfocadas a la ejecución material de un medio permanente que, sin embargo, sólo alcanzan su objetivo en forma de instalación de arte temporal. Como caso de estudio se considera Extreme Nature: Landscape of Ambiguous Spaces, el proyecto diseñado por Ishigami para el Pabellón de Japón en la 11a Mostra Internazionale di Architettura de la Biennale di Venezia de 2008.The work of Junya Ishigami has been a frequent object of study in the context of close-to-nature architecture, an area of interest shared by the constellation of Japanese architects between the end of the 20th century and the beginning of the 21st. This article looks at the work of Ishigami with a specific focus on nature as a construction laboratory, in line with the dual purpose of pieces to be exhibited in galleries or to be formalized as architecture. This parallel approach allows us to discuss the functionality of strategies that focus on the material implementation of permanent mediums that, however, only reach their goal as a temporary art installation. The case study chosen is “Extreme Nature: Landscape of Ambiguous Spaces”; the project designed by Ishigami for the Japanese Pavilion in the 11th Mostra Internazionale di Architettura at the Biennale di Venezia in 2008

Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion

Aims: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methods: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findings: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. Significance: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatmentsAC thanks to ANPCyT (Argentina) PICT 2014-0727 and CONICET (Argentina) PIP 2014 number 11220130100237CO. Lorena Rodriguez acknowledges CONICET fellowships, Bunge & Born Foundation Argentina and Jorge Oster, Argentina, for financial support. FS and AC acknowledge Ministerio de Asuntos Exteriores y Cooperación and Agencia Española de Cooperación Internacional para el Desarrollo (A/ 015883/08), Spain, for financial support. MAR is supported through a Junior Faculty Scholar Award from the American Society of Hematolog

Infrared-Emitting QDs for Thermal Therapy with Real-Time Subcutaneous Temperature Feedback

Nowadays, one of the most exciting applications of nanotechnology in biomedicine is the development of localized, noninvasive therapies for diverse diseases, such as cancer. Among them, nanoparticle-based photothermal therapy (PTT), which destroys malignant cells by delivering heat upon optical excitation of nanoprobes injected into a living specimen, is emerging with great potential. Two main milestones that must be reached for PTT to become a viable clinical treatment are deep penetration of the triggering optical excitation and real-time accurate temperature monitoring of the ongoing therapy, which constitutes a critical factor to minimize collateral damage. In this work, a yet unexplored capability of near-infrared emitting semiconductor nanocrystals (quantum dots, QDs) is demonstrated. Temperature self-monitored ­QD-based PTT is presented for the first time using PbS/CdS/ZnS QDs emitting in the second biological window. These QDs are capable of acting, simultaneously, as photothermal agents (heaters) and high-resolution fluorescent thermal sensors, making it possible to achieve full control over the intratumoral temperature increment during PTT. The differences observed between intratumoral and surface temperatures in this comprehensive investigation, through different irradiation conditions, highlight the need for real-time control of the intratumoral temperature that allows for a dynamic adjustment of the treatment conditions in order to maximize the efficacy of the therapyThis project has been supported by the Spanish Ministerio de Economía y Competitividad under project and MAT2013-47395-C4-1-R. B. del Rosal thanks Universidad Autónoma de Madrid for an FPI grant. F. Ren acknowledges scholarship support from the Fonds de recherche du Québec – Nature et technologies (FRQNT) under the Programme de Bourses d’Excellence (Merit Scholarship Program for Foreign Students

Potent Virucidal Activity In Vitro of Photodynamic Therapy with Hypericum Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E

The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new virucidal treatments. In this sense, the use of photodynamic therapy (PDT) with white light, to take advantage of the sunlight, is a potent strategy for decreasing the virulence and pathogenicity of the virus. Here, we report the virucidal effect of PDT based on Hypericum extract (HE) in combination with white light, which exhibits an inhibitory activity of the human coronavirus HCoV-229E on hepatocarcinoma Huh-7 cells. Moreover, despite continuous exposure to white light, HE has long durability, being able to maintain the prevention of viral infection. Given its potent in vitro virucidal capacity, we propose HE in combination with white light as a promising candidate to fight against SARS-CoV-2 as a virucidal compound

Optimum quantum dot size for highly efficient fluorescence bioimaging

Semiconductor quantum dots of few nanometers have demonstrated a great potential for bioimaging. The size determines the emitted color, but it is also expected to play an important role in the image brightness. In this work, the size dependence of the fluorescence quantum yield of the highly thermal sensitive CdTe quantum dots has been systematically investigated by thermal lens spectroscopy. It has been found that an optimum quantum yield is reached for 3.8-nm quantum dots. The presence of this optimum size has been corroborated in both one-photon excited fluorescence experiments and two-photon fluorescence microscopy of dot-incubated cancer cells. Combination of quantum yield and fluorescence decay time measurements supports that the existence of this optimum size emerges from the interplay between the frequency-dependent radiative emission rate and the size-dependent coupling strength between bulk excitons and surface trapping states

Vasoactive intestinal peptide axis is dysfunctional in patients with Graves’ disease

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves’ disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto’s thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.This work has been supported by Instituto de Salud Carlos III, Spain, cofinanced by FEDER, European Union: RETICS program, Red de Investigación en Inflamación y Enfermedades Reumáticas (RD16/0012/0008, PI17/00027, PI16-02091, PIE13-0004) and from Consejería de Educación, Juventud y Deporte, Comunidad de Madrid: B2017/BMD372

High resolution fluorescence imaging of cancers using lanthanide ion-doped upconverting nanocrystals

During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs), are already commercially available for this purpose. In this work we review the role which is being played by a relatively new class of nanoparticles, based on lanthanide ion doped nanocrystals, to target and image cancer cells using upconversion fluorescence microscopy. These nanoparticles are insulating nanocrystals that are usually doped with small percentages of two different rare earth (lanthanide) ions: The excited donor ions (usually Yb3+ ion) that absorb the NIR excitation and the acceptor ions (usually Er3+, Ho3+ or Tm3+), that are responsible for the emitted visible (or also near infrared) radiation. The higher conversion efficiency of these nanoparticles in respect to those based on QDs and GNRs, as well as the almost independent excitation/emission properties from the particle size, make them particularly promising for fluorescence imaging. The different approaches of these novel nanoparticles devoted to "in vitro" and "in vivo" cancer imaging, selective targeting and treatment are examined in this reviewJ.A.C. is a Concordia University Research Chair in Nanoscience and is grateful to Concordia University for financial support of his research. J.A.C. and F.V. are grateful for financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada. R.N. is grateful for NSERC financial support through the Alexander Graham Bell Graduate Scholarship Program. B.F.Z. is grateful to les Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT) for financial support through the Graduate Scholarship Program. This work was also supported in part by the Universidad Autónoma de Madrid and Comunidad Autónoma de Madrid (Projects CCG087-UAM/MAT-4434 and S2009/MAT-1756), by the Spanish Ministerio de Educación y Ciencia (MAT 2010–16161). EMR acknowledges financial support from Fundación Alfonso Martín Escudero and Marie Curie IOF Fellowship Program (project 274404 LUNAMED

Tumor microenvironment in non-melanoma skin cancer resistance to photodynamic therapy

Non-melanoma skin cancer has recently seen an increase in prevalence, and it is estimated that this grow will continue in the coming years. In this sense, the importance of therapy effectiveness has increased, especially photodynamic therapy. Photodynamic therapy has attracted much attention as a minimally invasive, selective and repeatable approach for skin cancer treatment and prevention. Although its high efficiency, this strategy has also faced problems related to tumor resistance, where the tumor microenvironment has gained a well-deserved role in recent years. Tumor microenvironment denotes a wide variety of elements, such as cancer-associated fibroblasts, immune cells, endothelial cells or the extracellular matrix, where their interaction and the secretion of a wide diversity of cytokines. Therefore, the need of designing new strategies targeting elements of the tumor microenvironment to overcome the observed resistance has become evident. To this end, in this review we focus on the role of cancer-associated fibroblasts and tumor-associated macrophages in the resistance to photodynamic therapy. We are also exploring new approaches consisting in the combination of new and old drugs targeting these cells with photodynamic therapy to enhance treatment outcomes of non-melanoma skin cance

The use of dipeptide derivatives of 5-aminolaevulinic acid promotes their entry to tumor cells and improves tumor selectivity of photodynamic therapy

The use of endogenous protoporphyrin IX generated after administration of 5-aminolaevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). However, the bioavailability of ALA is limited by its hydrophilic properties and limited cell uptake. A promising approach to optimize the efficacy of ALA-PDT is to deliver ALA in the form of prodrugs to mask its hydrophilic nature. The aim of this work was to evaluate the potential of two ALA dipeptide derivatives, N-acetyl terminated leucinyl-ALA methyl ester (Ac-Leu-ALA-Me) and phenylalanyl-ALA methyl ester (Ac-Phe-ALA-Me), for their use in PDT of cancer, by investigating the generation of protoporphyrin IX in an oncogenic cell line (PAM212-Ras), and in a subcutaneous tumor model. In our in vitro studies, both derivatives were more effective than ALA in PDT treatment, at inducing the same protoporphyrin IX levels but at 50- to 100-fold lower concentrations, with the phenylalanyl derivative being the most effective. The efficient release of ALA from Ac-Phe-ALA-Me appears to be consistent with the reported substrate and inhibitor preferences of acylpeptide hydrolase. In vivo studies revealed that topical application of the peptide prodrug Ac-Phe-ALA-Me gave greater selectivity than with ALA itself, and induced tumor photodamage, whereas systemic administration improved ALA-induced porphyrin generation in terms of equivalent doses administered, without induction of toxic effects. Our data support the possibility of using particularly Ac-Phe-ALA-Me both for topical treatment of basal cell carcinomas and for systemic administration. Further chemical fine-tuning of this prodrug template should yield additional compounds for enhanced ALA-PDT with potential for translation to the clinic