Femtosecond pulsed laser photodynamic therapy activates melanin and eradicates malignant melanoma.

Photodynamic therapy (PDT) relies on a series of photophysical and photochemical reactions leading to cell death. While effective for various cancers, PDT has been less successful in treating pigmented melanoma due to high light absorption by melanin. Here, this limitation is addressed by 2-photon excitation of the photosensitizer (2p-PDT) using ~100 fs pulses of near-infrared laser light.

Metabolic Lipids in Melanoma Enable Rapid Determination of Actionable BRAF-V600E Mutation with Picosecond Infrared Laser Mass Spectrometry in 10 s.

Rapid molecular profiling of biological tissues with picosecond infrared laser mass spectrometry (PIRL-MS) has enabled the detection of clinically important histologic types and molecular subtypes of human cancers in as little as 10 s of data collection and analysis time. Utilizing an engineered cell line model of actionable BRAF-V600E mutation, we observed statistically significant differences in 10 s PIRL-MS molecular profiles between BRAF-V600E and BRAF-wt cells. Multivariate statistical analyses revealed a list of mass-to-charge (/) values most significantly responsible for the identification of BRAF-V600E mutation status in this engineered cell line that provided a highly controlled testbed for this observation.

Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.

Background: This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis.

Methods: The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay.

Preclinical evaluation of Raman spectroscopy for pedicular screw insertion surgical guidance in a porcine spine model.

Significance: Orthopedic surgery is frequently performed but currently lacks consensus and availability of ideal guidance methods, resulting in high variability of outcomes. Misdirected insertion of surgical instruments can lead to weak anchorage and unreliable fixation along with risk to critical structures including the spinal cord. Current methods for surgical guidance using conventional medical imaging are indirect and time-consuming with unclear advantages.

Picosecond Infrared Laser Mass Spectrometry Identifies a Metabolite Array for 10 s Diagnosis of Select Skin Cancer Types: A Proof-of-Concept Feasibility Study.

Currently, a large number of skin biopsies are taken for each true skin cancer case detected, creating a need for a rapid, high sensitivity, and specificity skin cancer detection tool to reduce the number of unnecessary biopsies taken from benign tissue. Picosecond infrared laser mass spectrometry (PIRL-MS) using a hand-held sampling probe is reported to detect and classify melanoma, squamous cell carcinoma, and normal skin with average sensitivity and specificity values of 86-95% and 91-98%, respectively (at a 95% confidence level) solely requiring 10 s or less of total data collection and analysis time. Classifications are not adversely affected by specimen's quantity of melanin pigments and are mediated by a number of metabolic lipids, further identified herein as potential biomarkers for skin cancer-type differentiation, 19 of which were sufficient here (as a fully characterized metabolite array) to provide high specificity and sensitivity classification of skin cancer types.

Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2.

The lack of therapeutic options to fight Covid-19 has contributed to the current global pandemic. Despite the emergence of effective vaccines, development of broad-spectrum antiviral treatment remains a significant challenge, in which antimicrobial photodynamic therapy (aPDT) may play a role, especially at early stages of infection. aPDT of the nares with methylene blue (MB) and non-thermal light has been successfully utilized to inactivate both bacterial and viral pathogens in the perioperative setting.

Ex vivo treatment of cytomegalovirus in human donor lungs using a novel chemokine-based immunotoxin.

Background: Transmission of latent human cytomegalovirus (HCMV) via organ transplantation with post-transplant viral reactivation is extremely prevalent and results in substantial adverse impact on outcomes. Therapies targeting the latent reservoir within the allograft to mitigate viral transmission would represent a major advance. Here, we delivered an immunotoxin (F49A-FTP) that targets and kills latent HCMV aiming at reducing the HCMV reservoir from donor lungs using ex-vivo lung perfusion (EVLP).

A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied.

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles.

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill.

Volumetric tumor delineation and assessment of its early response to radiotherapy with optical coherence tomography.

Texture analyses of optical coherence tomography (OCT) images have shown initial promise for differentiation of normal and tumor tissues. This work develops a fully automatic volumetric tumor delineation technique employing quantitative OCT image speckle analysis based on Gamma distribution fits. We test its performance using immunodeficient mice with dorsal skin window chambers and subcutaneously grown tumor models.

Optical clearing agent increases effectiveness of photodynamic therapy in a mouse model of cutaneous melanoma: an analysis by Raman microspectroscopy.

Melanoma is the most aggressive type of skin cancer and a relevant health problem due to its poor treatment response with high morbidity and mortality rates. This study, aimed to investigate the tissue changes of an improved photodynamic therapy (PDT) response when combined with optical clearing agent (OCA) in the treatment of cutaneous melanoma in mice. Photodithazine (PDZ) was administered intraperitoneally and a solution of OCA was topically applied before PDT irradiation.

The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats.

Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats.

Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models.

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both.

Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion.

Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission.

Non-invasive dynamic assessment of conjunctival melanomas by photoacoustic imaging.

This study describes non-invasive photoacoustic imaging to detect and monitor the growth of conjunctival melanomas in vivo. Conjunctival melanomas were induced by injection of melanotic B16F10 cells into the subconjunctival space in syngeneic albino C57BL/6 mice. Non-invasive in vivo photoacoustic tomography was performed before, and after tumor induction up to 2 weeks.

Optical clearing of melanoma in vivo: characterization by diffuse reflectance spectroscopy and optical coherence tomography.

Melanoma is the most aggressive type of skin cancer, with significant risk of fatality. Due to its pigmentation, light-based imaging and treatment techniques are limited to near the tumor surface, which is inadequate, for example, to evaluate the microvascular density that is associated with prognosis. White-light diffuse reflectance spectroscopy (DRS) and near-infrared optical coherence tomography (OCT) were used to evaluate the effect of a topically applied optical clearing agent (OCA) in melanoma in vivo and to image the microvascular network.

Time-resolved fluorescence lifetime for cutaneous melanoma detection.

Melanoma is the most aggressive skin cancer type. It is characterized by pigmented lesions with high tissue invasion and metastatic potential. The early detection of melanoma is extremely important to improve patient prognosis and survival rate, since it can progress to the deadly metastatic stage.

Photobiological characteristics of chlorophyll a derivatives as microbial PDT agents.

Chlorin-e6 (chl-e6) and a hydrogenated derivative (chl-e6H) were semi-synthesized, and their photophysical properties and photodynamic activity against Escherichia coli, Staphylococcus aureus and Candida albicans evaluated. Methyl pheophorbide-a (Mepheo-a) was obtained from S. maxima using methanolic extraction with acid catalysis (CH3OH–H2SO4).

Photodynamic therapy in Pythium insidiosum - an in vitro study of the correlation of sensitizer localization and cell death.

Pythiosis is an infectious disease caused by Pythium insidiosum, a fungus-like organism. Due to the lack of ergosterol on its cell membrane, antibiotic therapy is ineffective. The conventional treatment is surgery, but lesion recurrence is frequent, requiring several resections or limb amputation.

Experience and BCC subtypes as determinants of MAL-PDT response: preliminary results of a national Brazilian project.

Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug.

Photodynamic therapy for pythiosis.

Background: Pythiosis is a life-threatening disease caused by Pythium insidiosum. Photodynamic therapy (PDT) is an alternative treatment to surgery that uses the interaction of a photosensitizer, light and molecular oxygen to cause cell death.

Objectives: To evaluate the effect of PDT on the in vitro growth of P.