A Dual-Locked Activatable Phototheranostic Probe for Biomarker-Regulated Photodynamic and Photothermal Cancer Therapy.

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual-locked activatable phototheranostic probe that activates near-infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor-periphery biomarker, and switches from PDT to PTT upon detecting a tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumor-core where is too hypoxic for PDT. This dual-locked probe represents a promising molecular design approach toward precise cancer phototheranostics.

Photobiomodulation by Near-Infrared 980-nm Wavelengths Regulates Pre-Osteoblast Proliferation and Viability through the PI3K/Akt/Bcl-2 Pathway.

BACKGROUND: bone tissue regeneration remains a current challenge. A growing body of evidence shows that mitochondrial dysfunction impairs osteogenesis and that this organelle may be the target for new therapeutic options. Current literature illustrates that red and near-infrared light can affect the key cellular pathways of all life forms through interactions with photoacceptors within the cells' mitochondria. The current study aims to provide an understanding of the mechanisms by which photobiomodulation (PBM) by 900-nm wavelengths can induce in vitro molecular changes in pre-osteoblasts. METHODS: The PubMed, Scopus, Cochrane, and Scholar databases were used. The manuscripts included in the narrative review were selected according to inclusion and exclusion criteria. The new experimental set-up was based on irradiation with a 980-nm laser and a hand-piece with a standard Gaussian and flat-top beam profile. MC3T3-E1 pre-osteoblasts were irradiated at 0.75, 0.45, and 0.20 W in continuous-wave emission mode for 60 s (spot-size 1 cm2) and allowed to generate a power density of 0.75, 0.45, and 0.20 W/cm2 and a fluence of 45, 27, and 12 J/cm2, respectively. The frequency of irradiation was once, three times (alternate days), or five times (every day) per week for two consecutive weeks. Differentiation, proliferation, and cell viability and their markers were investigated by immunoblotting, immunolabelling, fluorescein-FragELTM-DNA, Hoechst staining, and metabolic activity assays. RESULTS AND CONCLUSIONS: The 980-nm wavelength can photobiomodulate the pre-osteoblasts, regulating their metabolic schedule. The cellular signal activated by 45 J/cm2, 0.75 W and 0.75 W/cm2 consist of the PI3K/Akt/Bcl-2 pathway; differentiation markers were not affected, nor do other parameters seem to stimulate the cells. Our previous and present data consistently support the window effect of 980 nm, which has also been described in extracted mitochondria, through activation of signalling PI3K/Akt/Bcl-2 and cyclin family, while the Wnt and Smads 2/3-ß-catenin pathway was induced by 55 J/cm2, 0.9 W and 0.9 W/cm2.

Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy-From Animal Models to Clinical Trials.

The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

Assessment of stereopsis in unilateral amblyopia subjects using syntonic phototherapy.

INTRODUCTION: Amblyopia is two Snellen line difference between both eyes. Red filter therapy is a treatment option for amblyopia based on principle of syntonic phototherapy. The purpose of this study is to assess the stereopsis in amblyopic patient using syntonic phototherapy. METHODS: A Qusai experimental study was conducted from August 2021 to December 2021 at Madina Teaching Hospital Faisalabad. A total 30 subjects of both gender and ages ranging between 8 to 18 years were included through a non-probability purposive sampling technique. The sample was considered of 15 anisometropic amblyopes and 15 strabismic amblyope. Data was collected using a Performa and pre assessments of stereopsis by Titmus fly chart were recorded without red filter. Red filter glasses were prescribed for 4 week, post assessment data was recorded after 4 weeks. Data was analyzed by using Paired sample T test and Independent Sample T test in SPSS 20 software. RESULTS: After syntonic phototherapy significant improvement was seen, mean stereopsis was 48.00000 (p = 0.002) in anisometropic amblyopes while mean improvement of stereopsis 1.670.93333 (p = 0.00) in strabismic amblyopes. Anisometropic amblyopic patients showed significantly better improvement in stereopsis (p = 0.00) by syntonic phototherapy as compared to strabismic amblyopes. CONCLUSION: Significant improvement was seen in stereopsis, while improvement was more significant in anisometropic amblyopes as compared to strabismic amblyopes. Children were obsessed with the red filter glasses while their parents found syntonic therapy simple plus facile and gave good results. So, eye care professionals must be aware of this new therapy and they should keep syntonic phototherapy in mind whenever they are dealing with amblyopic patients.

Advent in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers to accomplish active or homologous tumor targeting for smart amalgamated chemotherapy/photo-therapy: A review.

Conventional cancer mono-therapeutic approaches including radiotherapy, surgery, and chemotherapy don't always achieve satisfactory outcomes and are frequently associated with significant limitations. Although chemotherapy is a vital intervention, its effectiveness is frequently inadequate and is associated with metastasis, multidrug resistance, off-target effect, and normal cells toxicity. Phototherapies are employed in cancer therapy, encompassing photo-dynamic and photo-thermal therapies which under favorable NIR laser light irradiation initiate the included photosensitizers and photo-thermal agents to generate ROS or thermal heat respectively for cancer cells destruction. Photo-therapy is considered noninvasive, posing no resistance, but it still suffers from several pitfalls like low penetration depth and excessive heat generation affecting neighboring tissues. Improved selectivity and tumor-homing capacity could be attained through surface modulation of nanoparticles with targeting ligands that bind to receptors, which are exclusively overexpressed on cancerous cells. Developing novel modified targeted nanoparticulate platforms integrating different therapeutic modalities like photo-therapy and chemotherapy is a topic of active research. This review aimed to highlight recent advances in proteins, nucleic acids, and biological cell membranes functionalized nanocarriers for smart combinatorial chemotherapy/photo-therapy. Nanocarriers decorated with precise targeting ligands, like aptamers, antibody, and lactoferrin, to achieve active tumor-targeting or camouflaging using various biological cell membrane coating are designed to achieve homologous tumor-targeting.

Combined chemo and photo therapy of programmable prodrug carriers to overcome delivery barriers against nasopharyngeal carcinoma.

Indocyanine green (ICG) has been employed in medical diagnostics due to its superior photophysical characteristics. However, these advantages are offset by its quick body clearance and inferior photo-stability. In this work, programmable prodrug carriers for chemotherapy/PDT/PTT against nasopharyngeal carcinoma (NPC) were created in order to increase photo-stability and get around biochemical hurdles. The programmable prodrug carriers (PEG-PLA@DIT-PAMAM) that proactively penetrated deeply into NPC tumors and produced the deep phototherapy and selective drug release under laser irradiation was created by dendrimer-DOX/ICG/TPP (DIT-PAMAM) and PEGylated poly (α-lipoic acid) (PLA) copolymer. Long circulation times and minimal toxicity to mammalian cells are two benefits of PEG-coated carriers. The overexpressed GSH on the tumor cell or vascular endothelial cell of the NPC disintegrated the PEG-g-PLA chains and released the DIT-PAMAM nanoparticles after the carriers had reached the NPC tumor periphery. Small, positively charged DIT-PAMAM nanoparticles may penetrate tumors effectively and remain inside tumor for an extended period of time. In addition, the induced ROS cleaved the thioketal linkers for both DOX and nanoparticles and product hyperthermia (PTT) to kill cancer cells under laser irradiation, facilitating faster diffusion of nanoparticles and more effective tumor penetration with a programmable publication of DOX. The programmable prodrug carries showed high photo-stability high photo-stability, which enabled very effective PDT, PTT, and tumor-specific DOX release. With the goal of combining the effects of chemotherapy, PDT, and PTT against NPC, this research showed the great efficacy of programmable prodrug carriers.

Facile preparation of indocyanine green and tiny gold nanoclusters co-loaded nanocapsules for targeted synergistic sono-/photo-therapy.

Photothermal therapy (PTT) and sono-photodynamic therapy (SPDT) are fast growing local treatment modalities with minimal invasiveness and high safety. Gold nanoparticles and indocyanine green (ICG) have been used as sensitizers for PTT and SPDT. However, long resident time of gold nanoparticles in tissues and fast elimination of ICG hampered their further clinical applications. Herein, we developed nanocapsules formed by hyaluronic acid and chitosan loading with ICG and tiny gold nanoclusters (TAuNCs) to overcome the shortcomings of gold nanoparticles and ICG for combined PTT and SPDT. The nanocapsules exhibited good biological stability, favorable photothermal effects, and ultrasound/near-infrared light (NIR)-responsive release behaviors. The hyaluronic acid could mediate the specific delivery of cargos to CD44 protein over-expressing cancer cells. The in vitro and in vivo results showed that TAuNCs and ICG could act synergistically to obtain satisfactory anticancer effects under NIR laser and/or ultrasound exposure induced by thermal ablation and reactive oxygen species (ROS) generation. Biodistribution and excretion studies showed that the nanocapsules had longer ICG retention time in tumor and most of the TAuNCs could be effectively excreted from the body within one month. This study thus provides a facile strategy for the development of a safe and high-performance nanoplatform for synergistic PTT/SPDT.

Recent Developments on Semiconducting Polymer Nanoparticles as Smart Photo-Therapeutic Agents for Cancer Treatments-A Review.

Semiconducting polymer nanoparticles (SPN) have been emerging as novel functional nano materials for phototherapy which includes PTT (photo-thermal therapy), PDT (photodynamic therapy), and their combination. Therefore, it is important to look into their recent developments and further explorations specifically in cancer treatment. Therefore, the present review describes novel semiconducting polymers at the nanoscale, along with their applications and limitations with a specific emphasis on future perspectives. Special focus is given on emerging and trending semiconducting polymeric nanoparticles in this review based on the research findings that have been published mostly within the last five years.

Comparison of the effect of foot reflexology and body massage on physiological indicators and bilirubin levels in neonates under phototherapy.

BACKGROUND: Hyperbilirubinemia is one of the most common problems in infancy in the world. The aim of this study was to compare the effect of foot therapy and body massage on physiological indicators and bilirubin levels in infants under phototherapy. METHODS: This study was a randomized clinical trial that conducted on 51 infants with jaundice at Imam Hussein Pediatrics' Medical Center, Goldis Hospital in Isfahan (Iran). The samples randomly assigned to first intervention (reflexology), second intervention (body massage) and control groups using the block randomization. In the reflexology group, the relevant area on each foot was massaged for 15 min in a relaxed position. In the massage body group, the limbs were massaged with circular motion. The massage was performed once a day for 15 min and the control group did not receive any intervention. Physiological indicators were monitored using vital sign monitoring tools, and blood bilirubin levels were measured photo metrically (intravenous blood samples from the wrist). Finally, the data were analyzed using descriptive and inferential statistics and SPSS software version 18. RESULTS: The results showed that before the intervention there was no significant difference in the mean of physiological indicators and bilirubin level between the three groups (p > 0.05), but after the intervention the average percentage of arterial oxygen saturation and bilirubin levels were significantly improved in the intervention groups compared to the control group (p < 0.05), while the mean of heart rate and respiration rate between the three groups were not significant (p > 0.05). CONCLUSION: The results showed that reflexology and massage therapy can be effective in improving the condition of physiological indicators and blood bilirubin levels.

Photothermal-pH-hypoxia responsive multifunctional nanoplatform for cancer photo-chemo therapy with negligible skin phototoxicity.

Highly specific and effective cancer phototherapy remains as a great challenge. Herein, a smart nanoplatform (TENAB NP) sequentially responsive to light, low pH and hypoxia is demonstrated for multi-mode imaging guided synergistic cancer therapy with negligible skin phototoxicity. Upon 808-nm laser irradiation, TENAB NPs can generate hyperthermia to melt the phase change material (PCM-LASA) coat and thereafter release chemo-drug tirapazamine (TPZ). Meanwhile, under acidic pH, photosensitizer ENAB would turn "off" its charge-transfer state, generating prominent 1O2 for photodynamic therapy (PDT) and heat for photothermal therapy (PTT), respectively. Accompanied with PDT-induced hypoxia, the released TPZ can be activated into its cytotoxic form for tumor cells killing. Notably, owing to phase change material LASA coat and ENAB's pH sensitivity, TENAB NPs show negligible photosensitization to skin and normal tissues. As the multi-stimuli responsive mechanism, TENAB NPs demonstrate a promising future in cancer photo-chemo theranostics with excellent skin protection.

"Before I die I want to ": An experience of death education among university students of social service and psychology.

The censorship of death and dying has removed the "memento mori" practices, and in order to reintroduce this practice, some "Before I die" projects have been increasingly implemented. Running in parallel, in the syllabi of social service and psychology students, some experiences of death education has commenced. This study illustrates the results of a qualitative research conducted on the "Before I die I want to …" Polaroid® Project (BIDIWT), which is divided into two phases. The first phase entails an analysis of the wishes collected from the United States, Japan, India, and Italy. The second phase refers to the analysis of the captions of the BIDIWT realized from two groups of undergraduates, with regard to the effect of such experience on their religiosity, representation of death, and fear of death.

Dextran coated Fe3O4 nanoparticles as a near-infrared laser-driven photothermal agent for efficient ablation of cancer cells in vitro and in vivo.

The photothermal effect of dextran coated Fe3O4 nanoparticles for cancer therapy is investigated in this work. The dextran/Fe3O4 nanoparticles were prepared by coprecipitation method. Results demonstrated that the dextran not only isolated the interior Fe3O4 nanoparticles from oxygen and water to enhance the photothermal stability, but also enhanced the biocompatibility of Fe3O4 nanoparticles. In vitro experiments indicated that dextran/Fe3O4 nanoparticles showed low toxicity to cells without any irradation. After near-infrared (NIR) laser irradiation, however, the viabilities of tumor cells were effectively suppressed. Further in vivo experimental studies found that mice tumor growth was significantly inhibited by the photothermal effect of dextran/Fe3O4 nanoparticles. After 28 days the tumor was completely cleared. These dextran/Fe3O4 nanoparticles have biosecurity and high photothermal efficiency at the same time, thus promising high clinical potential.

HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.

Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.

Fundamental questions to sun protection: A continuous education symposium on vitamin D, immune system and sun protection at the University of Zürich.

Since exposure to sunlight is a main factor in the development of non-melanoma skin cancer and there are associations between malignant melanoma and short-term intense ultraviolet (UV) exposure, particularly burning in childhood, strict protection from UV-radiation is recommended. However, up to 90% of all requisite vitamin D has to be formed within the skin through the action of the sun-a serious problem, for a connection between vitamin D deficiency, demonstrated in epidemiological studies, and various types of cancer and other diseases has been confirmed. A UVB-triggered skin autonomous vitamin D(3) synthesis pathway has recently been described, producing the active Vitamin D metabolite calcitriol. This cutaneous vitamin D(3) pathway is unique. Keratinocytes and dendritic cells can convert vitamin D to calcitriol. Cutaneous T cells activated in the presence of calcitriol express the chemokine receptor CCR10 attracting them to the chemokine CCL27 that keratinocytes express selectively in the epidermis, and migrate from dermal layers of the skin to the epidermis under UV radiation. Thus, calcitriol has endocrine roles beyond its calciotropic action, including cell growth and cancer prevention. Therefore, strict sun protection procedures to prevent skin cancer may induce the risk of vitamin D deficiency. As there is evidence that the protective effect of less intense solar radiation can outweigh its mutagenic effect, better balanced approaches to sun protection should be sought.

Hyper Immunoglobulin E Syndrome with Concomitant Folliculotropic Mycosis Fungoides in a Filipino child treated with Narrowband UVB Phototherapy: A case report

@#Hyper Immunoglobulin E Syndrome (HIES) is a primary immunodeficiency disorder characterized by the classic triad of recurrent staphylococcal abscesses, frequent airway infections, and increased serum immunoglobulin E. It is now widely accepted as a multisystem disorder with involvement of the skeletal, connective tissue, dental, and vascular systems. Lymphoma has been reported to occur at an increased frequency. Follicu-lotropic mycosis fungoides (FMF) is a rare variant of cutaneous T-cell lymphoma in which the neoplastic T lymphocytes display tropism for the follicular epithelium. We report a case of a 14-year old Filipino male with the classic type of HIES presenting with severe eczema associated with intractable pruritus, recurrent respiratory tract infections, cold abscesses, and a serum IgE of 9,350 IU/ml. Skin biopsy also revealed findings consistent with FMF. Narrowband UVB (NB-UVB) phototherapy was initiated three times a week with continuation of supportive medication. Patient reported significant relief of pruritus and gradual improvement of eczematous lesions after one month.

New photonic technologies for the treatment and diagnosis of hepatic diseases: an overview of the experimental work performed in collaboration, between Physics Institute of São Carlos and Ribeirão Preto Faculty of Medicine of the University of São Paulo / Novas tecnologias fotônicas no tratamento e diagnóstico de doenças hepáticas: uma revisão dos trabalhos experimentais realizados em colaboração, entre o Instituto de Física de São Carlos e a Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Recent advances in optical techniques have created a great range of possibilities for diagnosis and therapeutics in liver related diseases. With the uses of efficient light sources like lasers and LEDs (Light Emitting Diodes) it is possible to employ the light-tissue interaction to promote hepatic tissue regeneration after partial hepatectomy, to detect hepatocarcinoma and steatosis by utilizing optical fluorescence, to evaluate the metabolism of the liver during hepatic transplantation as well as to treat liver tumors. We present here an overview of the technique presently in development at the Ribeirâo Preto Faculty of Medicine - USP in cooperation with the Physics Institute of São Carlos -USP. The results obtained so far have been the subject of a list of publications and are here presented as an overview. A new perspective for modern application of optical techniques in different medical practices related to the liver is presented.

Recentes avanços em técnicas ópticas têm propiciado vasto campo de possibilidades tanto para o diagnóstico quanto para a terapêutica de doenças hepáticas.Com o uso de eficientes fontes de luz como o laser e Light emitting diodes (LED) é possível utilizar a interação luz-tecido para promover a regeneração hepática após hepatectomias parciais,detectar hepatocarcinoma, esteatose e outras alterações do fígado pelo uso da fluorescência óptica,para avaliar o metabolismo hepático durante o transplante de fígado e na abordagem diagnóstica e terapêutica de alterações hepatocelulares. Os autores apresentam uma ampla revisão de técnicas atualmente em desenvolvimento na Divisão de Gastroenterologia Cirúrgica da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo num trabalho cooperativo com o Instituto de Física de São Carlos da USP. Os resultados obtidos até agora têm sido motivo de lista de publicações que são aqui apresentados em forma de revisão. Uma nova perspectiva de moderna aplicação de técnicas ópticas em várias situações clínico-cirúrgicas relacionadas com o fígado é apresentada e amplamente discutida.