Manganese-coordinated nanoparticle with high drug-loading capacity and synergistic photo-/immuno-therapy for cancer treatments.

Stimulator of interferon genes (STING) agonists have shown promise in cancer treatment by stimulating the innate immune response, yet their clinical potential has been limited by inefficient cytosolic entry and unsatisfactory pharmacological activities. Moreover, aggressive tumors with "cold" and immunosuppressive microenvironments may not be effectively suppressed solely through innate immunotherapy. Herein, we propose a multifaceted immunostimulating nanoparticle (Mn-MC NP), which integrates manganese II (Mn2+) coordinated photosensitizers (chlorin e6, Ce6) and STING agonists (MSA-2) within a PEGylated nanostructure. In Mn-MC NPs, Ce6 exerts potent phototherapeutic effects, facilitating tumor ablation and inducing immunogenic cell death to elicit robust adaptive antitumor immunity. MSA-2 activates the STING pathway powered by Mn2+, thereby promoting innate antitumor immunity. The Mn-MC NPs feature a high drug-loading capacity (63.42 %) and directly ablate tumor tissue while synergistically boosting both adaptive and innate immune responses. In subsutaneous tumor mouse models, the Mn-MC NPs exhibit remarkable efficacy in not only eradicating primary tumors but also impeding the progression of distal and metastatic tumors through synergistic immunotherapy. Additionally, they contribute to preventing tumor recurrence by fostering long-term immunological memory. Our multifaceted immunostimulating nanoparticle holds significant potential for overcoming limitations associated with insufficient antitumor immunity and ineffective cancer treatment.

Tumor microenvironment ameliorative and adaptive nanoparticles with photothermal-to-photodynamic switch for cancer phototherapy.

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.

Aggregation-induced emission: Application in diagnosis and therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed.

GSH-responsive polymeric micelles-based augmented photoimmunotherapy synergized with PD-1 blockade for eliciting robust antitumor immunity against colon tumor.

Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.

Photobiological response of mast cells to green and red light-emitting diodes (LEDs) in cutaneous burns.

This study assessed the effects of red and green LEDs on mast cells (MCs) in third-degree burns in 75 Wistar rats, divided into control, red LED (RED), and green LED (GREEN) groups. Animals were irradiated daily with RED (630 nm, 300 mW, 0.779 W/cm2, 9 J/cm2, 30 s) and GREEN (520 nm, 180 mW, 0.467 W/cm2, 60 J/cm2, 30 s). Histological sections stained with toluidine blue were analyzed for total and subtype MCs. Standardized MC counting was performed across the viable lesion area, considering lesion margins, through intact connective tissue and the integrity of skin appendages. No statistically significant differences in MCs 2 (with released granules and intact cell border) were found between groups. Irradiated groups showed increased total MCs at 7, 14, and 21 days (p < 0.05), with a decrease in MCs 1 (intact MCs) at all time points compared to control (p < 0.05). Significant changes in MCs 3 (with massive degranulation and partial or complete disintegration of the cell border) degranulation were noted in RED at 7, 14, and 21 days (p < 0.009) and in GREEN at 14 (p < 0.009) and 32 days (p < 0.028). Results suggest red and green LEDs modulate MC recruitment and degranulation in third-degree burns.

Effects of Monochromatic Infrared Light on Painful Diabetic Polyneuropathy: Randomized Controlled Trial.

PURPOSE: To evaluate the effect of 890 nm Monochromatic Infrared Light (MIR) associated with a physical therapy protocol on pain in individuals with diabetic Distal Symmetric Polyneuropathy. METHODS: Randomized, parallel, double-blind controlled trial conducted with individuals randomly allocated into two groups: an experimental group (EG) with the application of 890 nm MIR associated with physical therapy and a control group that received the same treatment protocol without MIR application. Both groups underwent 18 treatment sessions and were followed up for 10 weeks. Pain assessment took place at four times using the instruments: Leeds Assessment of Neuropathic Symptoms and Signs, Douleur Neuropathique 4, and Brief Pain Inventory. Descriptive, inferential statistics and probabilistic estimates of the magnitude of the intervention's effect on neuropathic pain were used in data analysis (5% significance level). RESULTS: A total of 144 patients were allocated to groups. Lower levels of pain were observed for the EG after 6 weeks of intervention (p < .001) and 30 days after the intervention ended (p < .001). Pain intensity was lower and sleep quality improved (p < .001) for the experiment group, especially in people with severe pain. CONCLUSIONS: 890 nm MIR associated with a physical therapy protocol alleviated pain in people with Diabetic Painful Polyneuropathy after 6 weeks of follow-up, showing to be a promising alternative for the control of neuropathic pain due to diabetes mellitus. CLINICAL IMPLICATIONS: 890 nm MIR improves Painful Diabetic Polyneuropathy patient care due to relief of neuropathic pain.

COVID-19-Vaccination-Induced Localized Lichen Planus Successfully Treated With Phototherapy.

Lichen planus (LP) is an inflammatory autoimmune mucocutaneous disease with different forms and presentations. It mainly affects the skin and oral mucosa but could also affect genital mucosa, nails, hair, and, rarely, the larynx and esophagus. Since the start of the COVID-19 era, multiple cutaneous manifestations related to SARS-CoV-2 infection or vaccination have been reported. Different rare cases of lichen planus were reported after COVID-19 infection and vaccination. This report elaborates on and adds an additional case of localized cutaneous lichen planus (CLP) to the upper extremities, which developed after both doses of the mRNA vaccine and improved after phototherapy.

Phototherapy and mycosis fungoides: what's new?

The most common cutaneous T-cell lymphoma, mycosis fungoides (MF), is clinically characterized by erythematous-violaceous nodules and erythematous-scaly patches. In the early stages of MF, phototherapy is currently the first line of treatment and plays a significant role. This study aims to review and analyze the various phototherapy options for cutaneous lymphoma.

Skin-directed therapy and biologic response modifiers in mycosis fungoides.

The most common and widespread type of cutaneous T-cell lymphoma is mycosis fungoides (MF), and it has a multiphasic clinical and biological course, with early stages being indolent for many years and later stages being faster and more aggressive. The clinical stage has a significant impact on the management and course of treatment: in the early stages, skin-directed therapies (SDT) plus/or biologic response modifiers (BRM); in the later stages, radiotherapy and/or systemic therapies. Even though national and international societies and groups periodically update their clinical recommendations, there is still no universally accepted approach. This paper reviews and discusses the various SDT and BRM options, either separately or in combination.

Gambogic acid and IR780 self-assembled nanoparticles for combined chemo-phototherapy.

Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm2). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E, Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy.

Use of fenofibrate as adjuvant to phototherapy in unconjugated neonatal hyperbilirubinemia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Most neonates have neonatal jaundice, with 5-15% requiring phototherapy. Although phototherapy is beneficial, it can potentially extend hospital stays and cause harm. This study's purpose was to analyze the effects of fenofibrate and phototherapy on total serum bilirubin (TSB) levels at 24 and 48 hours (primary outcome) after intervention. Furthermore, the phototherapy duration and adverse events were also of interest (secondary outcome). METHODS: The study protocol was registered in the PROSPERO database. Articles were searched on EMBASE, PubMed, Cochrane Library, and Google Scholar. Study selection was done following PRISMA and risk of bias studies were conducted. The Review Manager 5.4 was used for the meta-analysis. RESULTS: Nine studies, including 610 newborns, were identified and included in the meta-analysis. This meta-analysis discovered a significant change in TSB levels at 24 hours after intervention (mean difference (MD) -0.96 (95% CI -1.09, -0.83), p <  0.00001) with low heterogeneity and at 48 hours after intervention (MD -1.75 (95% CI -2.26, -1.24), p <  0.00001) with high heterogeneity. Significant shortening of phototherapy duration was observed in the interventional group (MD -15.28 (95% CI -20.65, -9.90), p <  0.00001) with high heterogeneities. One of the nine studies reported a non-significant occurrence of abdominal distension and diarrhea in the fenofibrate group. CONCLUSION: Fenofibrate might be applied as an adjuvant in unconjugated neonatal hyperbilirubinemia to reduce the average total serum bilirubin and shorten the length of phototherapy.

Chitin-Assisted Synthesis of CuS Composite Sponge for Bacterial Capture and Near-Infrared-Promoted Healing of Infected Diabetic Wounds.

Diabetic wounds are prone to recurrent infections, often leading to delayed healing. To address this challenge, we developed a chitin-copper sulfide (CuS@CH) composite sponge, which combines bacterial trapping with near-infrared (NIR) activated phototherapy for treating infected diabetic wounds. CuS nanoparticles were synthesized and incorporated in situ within the sponge using a chitin assisted biomineralization strategy. The positively charged chitin surface effectively adhered bacteria, while NIR irradiation of CuS generated reactive oxygen species (ROS) heat and Cu2+ to rapidly damage the trapped bacteria. This synergistic effect resulted in an exceptional antibacterial performance against E. coli (∼99.9%) and S. aureus (∼99.3%). The bactericidal mechanism involved NIR-induced glutathione oxidation, membrane lipid peroxidation, and increased membrane permeability. In diabetic mouse models, the CuS@CH sponge accelerated the wound healing of S. aureus infected wounds by facilitating collagen deposition and reducing inflammation. Furthermore, the sponge demonstrated good biocompatibility. This dual-functional platform integrating bacterial capture and NIR-triggered phototherapy shows promise as an antibacterial wound dressing to promote healing of infected diabetic wound.

Factors Influencing Adherence to Phototherapy in Patients With Psoriasis: A Cross-Sectional Study.

AIMS: Assess the level of adherence to phototherapy and determine what factors influence it. DESIGN: Cross-sectional. METHODS: This study included a convenience sampling of 72 patients with psoriasis undergoing phototherapy. Data were collected through a self-reported questionnaire with sociodemographic variables, the Goldberg Anxiety and Depression Scale, the Short Form Health Survey and the Dermatology Life Quality Index. Adherence to the treatment and its ending was measured through a session record. RESULTS: A small percentage of the participants demonstrated adequate adherence, and nearly half of them had low adherence. The factors statistically significant and with a negative impact on adherence were as follows: having a partner, experiencing anxiety or depression or using public transportation to get to the hospital. The probability of not adhering to the treatment increased when: patients found it difficult to attend therapy; perceiving their mental and physical health as being worse; experiencing anxiety or depression; having a diagnosed mental illness; being a man; or having had the sickness for an extended period of time. CONCLUSION: This study determined the level of adherence to phototherapy and advanced our understanding of this variable. Women exhibited higher levels of adherence compared to men, although they reported worse perceived mental and physical health, and the disease had a higher impact on their life. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Informing phototherapy nurses on the factors that impact treatment adherence may help to increase the treatment compliance, which may improve psoriasis patients' clinical symptoms. IMPACT: Increase the body of knowledge about the treatment that phototherapy nurses administer. REPORTING METHOD: STORBE guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A Supramolecular Nanoformulation with Adaptive Photothermal/Photodynamic Transformation for Preventing Dental Caries.

In the context of an increasingly escalating antibiotics crisis, phototherapy has emerged as a promising therapeutic approach due to its inherent advantages, including high selectivity, noninvasiveness, and low drug resistance. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two complementary and promising phototherapies albeit with inherent limitations, noted as the challenges in achieving precise heat confinement and the associated risk of off-target damage for PTT, while the constraints due to the hypoxic microenvironment are prevalent in biofilms faced by PDT. Herein, we have designed a supramolecular nanoformulation that leverages the complexation-induced quenching of guanidinium-modified calix[5]arene grafted with fluorocarbon chains (GC5AF5), the efficient recognition of adenosine triphosphate (ATP), and the oxygen-carrying capacity of the fluorocarbon chain. This intelligent nanoformulation enables the adaptive enhancement of both photothermal therapy (PTT) and photodynamic therapy (PDT), allowing for on-demand switching between the two modalities. Our nanoformulation utilizes ATP released by dead bacteria to accelerate the elimination of biofilms, rendering bacteria unable to resist while minimizing harm to healthy tissues. This research highlights the particular recognition and assembly capabilities of macrocycles, offering a promising strategy for creating potent, combined antibiofilm therapies.

Effects of high-intensity laser therapy on subacromial impingement syndrome: a systematic review and meta-analysis.

This systematic review and meta-analysis aims to identify, critically appraise, and summarize the effects of high-intensity laser therapy on subacromial impingement syndrome. Three databases, PubMed, Embase, and Scopus were searched from inception to March 1, 2024. Clinical trials comparing the effects of high-intensity laser therapy to conventional therapy are eligible for inclusion. Two independent reviewers conducted study selection, data extraction, and quality assessment. Methodological quality was assessed using the Physiotherapy Evidence Database scale. Meta-analyses were performed to determine the effects of high-intensity laser therapy. Five randomized controlled trials and one controlled clinical trial were included, with a total of 284 patients with subacromial impingement syndrome. All included studies were evaluated as good or above for quality assessment. Compared to conventional therapy, high-intensity laser therapy demonstrated significantly better outcomes for pain at both post-intervention (SMD = -1.01, 95%CI = -1.85 to -0.17) and three-month post-intervention (SMD = -0.51, 95%CI = -0.90 to -0.13); shoulder and arm function at both post-intervention (SMD = 0.40, 95%CI = 0.14 to 0.66) and three-month post-intervention (SMD = 0.45, 95%CI = 0.06 to 0.84); shoulder abduction active range of motion (SMD = 3.26, 95%CI = 0.49 to 6.03). No significant difference was found for shoulder flexion and external rotation range of motion. This review highlights the promising effects of high-intensity laser therapy for the rehabilitation of subacromial impingement syndrome. Rehabilitation professionals and policymakers should increase their awareness of high-intensity laser therapy as an emerging technology that may facilitate greater outcomes than current widespread standards.

The influence of phototherapy on circadian melatonin and sleep regulation and potential benefits of these pathways in the management of vitiligo: a narrative review : Vitiligo, phototherapy, sleep and melatonin.

Ultraviolet B narrow band (UVB-NB) phototherapy is the gold standard treatment for vitiligo, primarily due to its immunomodulatory effects. Additionally, it may influence circadian melatonin balance, that may indirectly induce sleep regulation, which in turn could potentially contribute to vitiligo improvement. The association between melatonin, vitiligo and phototherapy has been little investigated. The aim of this study was to evaluate the current evidence regarding the effects of circadian melatonin regulation and sleep, particularly during vitiligo treatment with phototherapy. We undertook a narrative review to synthetize the evidence on this association through the MEDLINE/PubMed database, using combined search terms: melatonin, vitiligo, phototherapy, and circadian rhythm (sleep). A total of 56 articles were included. There are few studies on this relationship, and conflicting findings. Some studies have suggested that UV exposure and phototherapy might benefit vitiligo by stimulating melanocytes, which have melatonin receptors, and this could potentially synchronize the circadian regulation of melatonin. This improved melatonin balance could result in better sleep quality further enhancing the antiinflammatory properties of melatonin and contributing to vitiligo improvement. Less is known about the possible effects of the use of topical melatonin, with or without phototherapy, to treat vitiligo lesions. In conclusion, there is some evidence that circadian melatonin regulation plays an important role in the course of vitiligo, both through sleep regulation and its anti-inflammatory properties. The evidence suggests that the systemic and physiological properties of melatonin, especially its circadian behavior regulated by phototherapy, may be more effective in respect of vitiligo improvement than the use of topical melatonin. However, the effects of the oral intake of melatonin are less clear. Phototherapy, as a potential modulator of circadian melatonin rhythm, that influences sleep and clinical improvement of vitiligo, needs further examination, as does the use of melatonin as an adjuvant treatment to UVB phototherapy in vitiligo.

Fabrication of a novel macrophage-targeted biomimetic delivery composite hydrogel with multiple-sensitive properties for tri-modal combination therapy of rheumatoid arthritis.

In this study, a porous polydopamine (PDA) nanoparticle-decorated ß-glucan microcapsules (GMs) nanoplatform (PDA/GMs) were developed with macrophage-targeted biomimetic features and a carriers-within-carriers structure. Indocyanine green (ICG) and catalase (CAT) were subsequently co-encapsulated within the PDA/GMs to create a multifunctional nanotherapeutic agent, termed CIPGs. Furthermore, CIPGs and sinomenine (SIN) were co-loaded within a thermo-sensitive hydrogel to design an injectable delivery system, termed CIPG/SH, with potential for multi-modal therapy of rheumatoid arthritis (RA). Photothermal studies indicated that the CIPGs hold excellent photothermal conversion ability and thermal stability, as they combined the photothermal performance of both PDA and ICG. Meanwhile, the CIPGs displayed favorable oxygen self-supplying and photodynamic performance. The CIPGs showed near-infrared (NIR)-induced phototoxicity, effectively inhibiting macrophage proliferation and displaying remarkable antibacterial activity. In vitro drug release from the prepared CIPG/SH showed a controlled release pattern. Animal experiments conducted on an RA mice model confirmed that the formulated CIPG/SH exhibited significant therapeutic effects. By integrating the biological advantages, photothermal/photodynamic performance of the CIPGs, and controlled drug release performance of the thermo-sensitive hydrogels in a single delivery system, the prepared injectable CIPG/SH represents a novel versatile delivery system with great potential for multi-modal combination targeting therapy in RA.