Light Dose Research Articles

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion

PurposeWe aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL).MethodsRetrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48–72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2.ResultsThe mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT.ConclusionsHiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

Deep Red Light Driven Hydrogen Evolution by Heterojunction Polymer Dots for Diabetic Wound Healing.

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge ⋅OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo-Pdots nanoreactors effectively scavenged ⋅OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.

Intraoperative photodynamic therapy in the structure of complex treatment of patients suffering from recurrence and continued growth of intracranial meningioma

The effectiveness and safety of intraoperative photodynamic therapy in patients with recurrent intracranial meningiomas were examined. Intraoperative photodynamic therapy was performed in three patients suffering from relapse and continued growth of histologically confirmed intracranial meningiomas of supratentorial localization. Intraoperative photodynamic therapy was conducted with consent from patients and was confirmed by a medical commission. We used a photosensitizer of the chlorin e6 group — photoditazine (Veta-Grand, Russia). The drug was administered intravenously at a dose of 1 mg/kg during induction of anesthesia. For irradiation, laser installation Latus (ATKUS, St. Petersburg, Russia) with a power of 2.5 W and wavelength of 662 nm was used. Irradiation was conducted in a continuous mode; the duration of therapy depended on the area of the irradiated surface based on a therapeutic light dose of 180 J/cm2. In the early postoperative period, the patients’ eyes were protected for 24 h from exposure to direct sunlight, and clinical, laboratory, and intrascopic controls were carried out. No complications associated with intraoperative photodynamic therapy were observed in the early postoperative period. On control intrascopy (magnetic resonance imaging in DWI, Flair, T2, T1 + contrast modes), data showing the therapeutic effect of intraoperative photodynamic therapy were obtained. In two cases, changes in tumor tissue and its matrix were confirmed pathomorphologically, indicating the therapeutic effect of intraoperative photodynamic therapy in relation to local control of meningiomas. Thus, the use of intraoperative photodynamic therapy in the complex treatment of patients suffering from a recurrent course of the neoplastic process (“aggressive” meningiomas) reveals its effectiveness for increasing the degree of radicality of the operation and safety. Further development of the technology of intraoperative photodynamic therapy is crucial in treating patients with “aggressive” meningiomas.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL−1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Microbial reduction of prebagged human plasma using 405 nm light and its effects on coagulation factors

Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm−2; ≤ 403 J cm−2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm−2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm−2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis.This PSFAA was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα.Final PSFAA, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6).This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.

A multi-step approach: Coupling of biodegradation and UV photocatalytic oxidation TiO2 for the treatment of naphthenic acid fraction compounds in oil sands process-affected water

Bitumen extraction in Alberta's oil sands region uses large volumes of water, leading to an abundance of oil sands process-affected water (OSPW). OSPW contains naphthenic acid fraction compounds (NAFCs) which have been found to contribute to OSPW toxicity. This study utilized a multistep treatment, coupling biological degradation with UV photocatalytic oxidation, and nutrient addition to boost the native microbial community's degradation capacity. OSPW initially contained 40–42 mg/L NAFCs with a toxicity of 3.8–3.9 TU. Initial biodegradation (Step 1) was used to remove the easily biodegradable NAFCs (11–25% removal), followed by a light or heavy dose of oxidation (Step 2) to breakdown the recalcitrant NAFCs (66–82% removal). Lastly, post-oxidation biodegradation with nutrients (Step 3) removed the residual bioavailable NAFCs (16–31% removal). By the end of the multistep treatment, the final NAFC concentrations and toxicity ranged from 5.3 to 6.8 mg/L and 1.1–1.2 TU. Analysis showed that OPSW was limited in phosphorus (below detection limit), and the addition of nutrients improved the degradation of NAFCs. Two treatments throughout the multistep treatment never received nutrients and showed minimal NAFC degradation post-oxidation. The native microbial community survived the stress from UV photocatalytic oxidation as seen by the post-oxidation NAFC biodegradation. Microbial community diversity was reduced considerably following oxidation, but increased with nutrient addition. The microbial community consisted predominately of Proteobacteria (Gammaproteobacteria and Alphaproteobacteria), and the composition shifted depending on the level of oxidation received. Possible NAFC-degrading microbes identified after a light oxidation dose included Pseudomonas, Acinetobacter and Xanthomonadales, while Xanthobacteracea and Rhodococcus were the dominant microbes after heavy oxidation. This experiment confirms that the microbial community is capable of degrading NAFCs and withstanding oxidative stress, and that degradation is further enhanced with the addition of nutrients.

Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).

TPS4204 Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells. We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber. Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment. Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.

Studying the viability and growth kinetics of vancomycin-resistant Enterococcus faecalis V583 following femtosecond laser irradiation (420–465 nm)

Enterococcus faecalis is among the most resistant bacteria found in infected root canals. The demand for cutting-edge disinfection methods has rekindled research on photoinactivation with visible light. This study investigated the bactericidal activity of femtosecond laser irradiation against vancomycin-resistant Enterococcus faecalis V583 (VRE). The effect of parameters such as wavelength and energy density on the viability and growth kinetics of VRE was studied to design an optimized laser-based antimicrobial photoinactivation approach without any prior addition of exogenous photosensitizers. The most effective wavelengths were 430 nm and 435 nm at a fluence of 1000 J/cm2, causing a nearly 2-log reduction (98.6% and 98.3% inhibition, respectively) in viable bacterial counts. The colony-forming units and growth rate of the laser-treated cultures were progressively decreased as energy density or light dose increased at 445 nm but reached a limit at 1250 J/cm2. At a higher fluence of 2000 J/cm2, the efficacy was reduced due to a photobleaching phenomenon. Our results highlight the importance of optimizing laser exposure parameters, such as wavelength and fluence, in bacterial photoinactivation experiments. To our knowledge, this is the first study to report an optimized wavelength for the inactivation of VRE using visible femtosecond laser light.

Cytotoxic and Immunomodulatory Effects of Hypericin as a Photosensitizer in Photodynamic Therapy Used on Skin Cell Cultures.

Determination of the hypericin-photodynamic (HY-PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY-PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY-PDT for HEKa and HDFa lines. After using HY-PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY-PDT. Our experiment confirmed that HY-PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY-PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods.

Enhanced antimicrobial efficacy and energy efficiency of low irradiance 405-nm light for bacterial decontamination

Due to its increased safety over ultraviolet light, there is interest in the development of antimicrobial violet-blue light technologies for infection control applications. To ensure compatibility with exposed materials and tissue, the light irradiances and dose regimes used must be suitable for the target application. This study investigates the antimicrobial dose responses and germicidal efficiency of 405 nm violet-blue light when applied at a range of irradiance levels, for inactivation of surface-seeded and suspended bacteria. Bacteria were seeded onto agar surfaces (101–108 CFUplate−1) or suspended in PBS (103–109 CFUmL−1) and exposed to increasing doses of 405-nm light (≤ 288 Jcm−2) using various irradiances (0.5–150 mWcm−2), with susceptibility at equivalent light doses compared. Bacterial reductions ≥ 96% were demonstrated in all cases for lower irradiance (≤ 5 mWcm−2) exposures. Comparisons indicated, on a per unit dose basis, that significantly lower doses were required for significant reductions of all species when exposed at lower irradiances: 3–30 Jcm−2/0.5 mWcm−2 compared to 9–75 Jcm−2/50 mWcm−2 for low cell density (102 CFUplate−1) surface exposures and 22.5 Jcm−2/5 mWcm−2 compared to 67.5 Jcm−2/150 mWcm−2 for low density (103 CFUmL−1) liquid exposures (P ≤ 0.05). Similar patterns were observed at higher densities, excluding S. aureus exposed at 109 CFUmL−1, suggesting bacterial density at predictable levels has minimal influence on decontamination efficacy. This study provides fundamental evidence of the greater energy efficacy of 405-nm light for inactivation of clinically-significant pathogens when lower irradiances are employed, further supporting its relevance for practical decontamination applications.

Activating Iterative Revolutions of the Cancer-Immunity Cycle in Hypoxic Tumors with a Smart Nano-Regulator.

The activation of sequential events in the cancer-immunity cycle (CIC) is crucial for achieving effective antitumor immunity. However, formidable challenges, such as innate and adaptive immune resistance, along with the off-target adverse effects of nonselective immunomodulators, persist. In this study, a tumor-selective nano-regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity. PNBJQ is obtained by encapsulating the immunomodulating agent JQ1 within a self-assembling system formed by linking a Type-I photosensitizer to polyethylene glycol through a hypoxia-sensitive azo bond. Benefiting from the Type-I photosensitive mechanism, PNBJQ triggers the immunogenic cell death of hypoxic tumors under near-infrared (NIR)light irradiation. This process resolves innate immune resistance by stimulating sufficient cytotoxic T-lymphocytes. Simultaneously, PNBJQ smartly responds to the hypoxic tumor microenvironment for precise drug delivery, adeptly addressing adaptive immune resistance by using JQ1 to downregulate programmed death ligand 1 (PD-L1) and sustaining the response of cytotoxic T lymphocytes. The activatable synergic photoimmunotherapy promotes an immune-promoting tumor microenvironment by activating an iterative revolution of the CIC, which remarkably eradicates established hypoxic tumors and suppresses distal lesions under low light dose irradiation.

Long term follow-up of patients with newly diagnosed glioblastoma treated by intraoperative photodynamic therapy: an update from the INDYGO trial (NCT03048240)

PurposeGlioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).MethodsTen patients were included (May 2017 – April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.ResultsAt the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7–71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan–Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).ConclusionAt 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.Trial registration NCT numberNCT03048240. EudraCT number: 2016–002706-39.

Preparation and pharmacological evaluation of A3B-type tetraphenyltetrabenzoporphyrins for photodynamic anti-tumor therapy

A series of A3B-type meso-tetraphenyltetrabenzoporphyrin photosensitizers were designed, synthesized and evaluated. All new compounds exhibited an intense Soret band at ∼ 470 nm and three Q bands at ∼ 595, ∼ 648, and ∼ 701 nm. They all had the ability to produce singlet oxygen upon photoexcitation, and photodynamic activities towards human esophageal carcinoma (Eca-109) cancer cells in vitro. Among them, 5 displayed the excellent cytotoxic effect on Eca-109 cells with the cell viability of ∼30 % at the concentration of 0.5 μM under a light dose of 12 J/cm2. 5 also could induce cell apoptosis after laser irradiation, and display superior photodynamic activity towards Eca-109 cells in vivo. Notably, inflammation and nuclear shrinkage of tumors were observed in the 5-PDT group, while no obvious changes were presented in major organs (heart, kidney liver, lung, and spleen) of mice, and the weight of mice were increased steadily during the treatment period. Hence, compound 5 possesses high photodynamic efficacy and good biosafety, and deserves to be considered as a potential photodynamic drug candidate for cancers.

The effect of near-infrared low-level light on the in vitro quality of platelets during storage.

Near-infrared (NIR) light has been successfully applied to improve the quality of mouse platelets during storage. Because it is suspected that the mitochondria contain the primary photon acceptor, we hypothesized that human platelets for transfusion may be affected similarly and could benefit from NIR light treatment. The optimal light dose was determined using portions of platelet concentrates (PCs) in PAS-E. A pool-and-split design was used to prepare PCs in PAS-E or plasma (n = 6). On day 1, one unit of both pairs was illuminated with 830 nm light (light-emitting diodes, 15 J/cm2). PCs were stored at 22°C and sampled regularly for analysis. Data were compared with their corresponding controls with a paired two-sided t-test. Illuminated platelets in PAS-E were less activated with significantly lower CD62P expression (day 8: 10.8 ± 1.8 vs. 12.2 ± 2.6, p < 0.05) and lower Annexin A5 binding (day 8: 11.8 ± 1.9 vs. 13.1 ± 2.4, ns). They produced significantly less lactate resulting in a higher pH (days 6-10). ATP content and mitochondrial membrane potential were not affected. Although these trends were also observed for PCs in plasma, the differences did not reach statistical significance as compared with the control group. Our study demonstrates that the glycolysis rate of human platelets can be modulated through the use of NIR, possibly through mitochondrial aerobic metabolism, but this requires confirmation. If NIR illumination can be further optimized, it may potentially become a useful tool in situations in which glycolysis and platelet activation are exacerbated.

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = –0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = –1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.Graphical

Effectiveness of broadband pulsed light and anti-inflammatory doses of minocycline in patients with papulopustular acne

Аbstract. Relevance. Over the past decades, laser devices have been regarded as the method of choice in the treatment of a wide range of skin conditions, including acne. This is the reason for the active search for new methods of therapy, adherence to which in patients with acne would be higher. From this point of view, the increase in the efficiency of broadband pulsed light (IPL) in combination with low doses of minocycline has all the prerequisites for inclusion in the therapeutic complex in the treatment of patients with acne. Purpose of the study. To study the efficacy and safety of using a combined method of therapy with broadband pulsed light and low doses of minocycline in patients with papulopustular acne, taking into account the concentration of MMP-1, MMP-2, MMP-3, MMP-9 in blood serum and the DISS index. Material and methods. Under observation were 100 patients (76 women) and (24 men) aged 18 to 45 years with a diagnosis of papulopustular form of acne, moderate severity. All patients, depending on the initial violation of the skin microbiota, were divided into two groups: group 1–50 patients, group 2–50 patients, each group was divided into subgroups depending on the type of therapy: subgroup A — 25 patients, subgroup B — 25 patients. All patients underwent a study of the concentration of MMP-1, MMP-2, MMP-3, MMP-9 in the blood serum. Research results. The results of comparing the levels of MMP-1, 2, 3, 9 and the DISHS index before and after various methods of therapy in patients with papulopustular acne, of moderate severity in subgroups 1B and 2B showed a more significant trend towards a decrease in MMP-1, 2, 3, 9 and the DISHS index relative to subgroups 1A and 2A. Conclusions. Analyzing the results of the study, we can conclude that the use of a combined method of treatment in patients with papulopustular form of acne, of moderate severity, demonstrated greater efficiency in the dynamics of reducing the levels of MMP-1, 2, 3, 9 concentrations, as well as reducing the total index DISH compared with low-dse minocycline and a topical retinoid.

Methods for assessing and removing non-specific photoimmunotherapy damage in patient-derived tumor cell culture models.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has been shown to selectively destroy tumor in a metastatic mouse model. However, the photoimmunoconjugate (PIC) used for taPIT includes a small fraction of non-covalently associated (free) benzoporphyrin derivative (BPD), which leads to non-specific killing invitro. Here, we report a new treatment protocol for patient-derived primary tumor cell cultures ultrasensitive to BPD photodynamic therapy (BPD-PDT). Based on free BPD efflux dynamics, the updated invitro taPIT protocol precludes non-specific BPD-PDT by silencing the effect of free BPD. Following incubation with PIC, incubating cells with PIC-free medium allows time for expulsion of free BPD whereas BPD covalently bound to PIC fragments is retained. Administration of the light dose after the intracellular free BPD drops below the threshold for inducing cell death helps to mitigate non-specific damage. In this study, we tested two primary ovarian tumor cell lines that are intrinsically chemoresistant, yet ultrasensitive to BPD-PDT such that small amounts of free BPD (afew percent of the total BPD dose) lead to potent induction of cell death upon irradiation. The modifications in the protocol suggested here improve invitro taPIT experiments that lack invivo mechanisms of free BPD clearance (i.e., lymph and blood flow).

Multi-color dual wavelength vat photopolymerization 3D printing via spatially controlled acidity

Dual wavelength vat photopolymerization (DW-VP) has emerged as a powerful approach to create multimaterial objects. However, only a limited range of properties have been showcased. In this work, we report the 3D printing (3DP) of multi-color objects from a single resin vat using DW-VP. This was accomplished by concurrently curing resin with visible light and modulating local resin color with 365-nm ultraviolet (UV) light. The key advance was to use a photoacid generator (PAG) in combination with pH responsive dyes in the 3DP resins. The specific color is dictated by the extent of reaction, or local acidity in our case, and controlled by the light dosage and pattern of UV light applied. Multi-color object formation was implemented in two-step processes involving first 3DP to set the object structure, followed by UV exposure, as well as single processes that leveraged DW-VP to create a broad range of vibrant colors and patterns.