Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Photodynamic therapy in the treatment of the right buccal mucosa verrucous carcinoma: a case report and literature review / 口腔疾病防治

Objective@#To explore the photodynamic treatment method and therapeutic effect of oral verrucous carcinoma and to provide a reference for the clinic.@*Methods@#This study follows the requirements of medical ethics. This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.@*Results@#After four rounds of photodynamic therapy, the size of the right buccal lesion was significantly reduced. After 6 months of follow-up, the white verrucous hyperplasia of the right buccal mucosa had completely subsided, and there was no obvious scar formation. Three years after treatment, there was no recurrence of the lesion in the right buccal mucosa and no obvious scar formation in the treated area. The degree of mouth opening was 3 fingers, and there was no lymph node enlargement in the bilateral submandibular, submental or neck. The literature review shows that oral verrucous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth, low malignancy, and rare metastasis. Surgery is the preferred treatment, but there are some limitations. Photodynamic therapy is a minimally invasive, repeatable treatment with mild adverse reactions. In recent years, photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results, but it has not been reported for the treatment of oral verrucous cancer@*Conclusion@#Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Synthesis and biological activities of chlorin e6-based conjugate of fluorouracil as dual-mode antitumor photosensitizer / 药学实践杂志

Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 171- and 152 cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, 1H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.

Terapia fotodinâmica para ação bactericida em úlceras venosas de usuários do serviço público de saúde / Photodynamic therapy for bactericidal action on venous ulcers of users of public health service

Introdução: As úlceras de difícil cicatrização caracterizam-se como uma patologia que afeta cerca de 20 milhões de pessoas pelo mundo. A terapia fotodinâmica TFD é um método que atua nas fases da cicatrização, bioestimulando o tecido e promovendo a morte dos microorganismos Objetivo: O objetivo deste estudo foi avaliar a TFD como técnica de ação bactericida na cicatrização das úlceras de usuários de um serviço público de saúde acometidos por úlceras venosas UV. Métodos: Para avaliar a presença de bactérias nas úlceras, foi utilizado um swab stuart. Foi aplicado o medicamento à base de curcumina na úlcera e a mesma foi imediatamente ocluída com papel alumínio durante 20 minutos. Resultados: Durante todo período de coleta houve crescimento de bactérias nas úlceras. Os participantes obtiveram redução da área das úlceras, avaliadas pela quantificação do software Image J Conclusão: A TFD foi capaz de acelerar o tempo de cicatrização de úlceras venosas, ao efeito bactericida, a técnica carece ainda de mais estudos.

Introduction: Ulcers that are difficult to heal are characterized as a pathology that affects about 20 million people around the world. PDT photodynamic therapy is a method that acts in the healing phases, biostimulating the tissue and promoting the death of microorganisms affected by UV. Methods: To assess the presence of bacteria in the ulcers, a stuart swab was used. the medicine based on curcumin was applied to the ulcer and it was immediately occluded with aluminum foil for 20 minutes. Results: During the entire collection period, there was growth of bacteria in the ulcers. The participants obtained a reduction in the area of the ulcers, evaluated by the quantification of the Image J software. Conclusion: PDT was able to accelerate the healing time of venous ulcers, due to its bactericidal effect, the technique still needs further studies.

Effect of different disinfection protocols in bacterial viability of an intraradicular biofilm formed in situ

Abstract The present study aimed to evaluate bacterial viability after the use of different disinfection protocols in root canals infected with a multispecies biofilm (MB) formed in situ. Palatal roots with a single canal were obtained from extracted maxillary molars and sterilized before being inserted into the mouth. The roots were contaminated with a MB in an intraoral appliance worn by ten volunteers. All volunteers wore six roots simultaneously in two intraoral devices for 21 days. One root from each volunteer was assigned to each group (n=10): PUI - passive ultrasonic irrigation; EC - Easy Clean; XPF - XP-endo Finisher; aPDT - antimicrobial photodynamic therapy; CI - conventional irrigation; and NC - negative control. The samples were evaluated under confocal laser scanning microscopy. The percentage of viable cells (VC) was calculated over the total percentage of MB biovolume. Data were statistically analyzed (α=5%). The cell viability in the entire root canal or for each third was compared between groups (Kruskal-Wallis test, Dunn post-hoc test) and for the same group (Friedman test, Dunn post-hoc test). Disinfection protocols were not significantly different from each other (P>.05). Samples in EC, PUI, and aPDT had lower cell viability than in NC (P<.05). In the coronal third of samples in the EC, XPF, PUI and aPDT, the percentage of VC biovolume was lower than in the NC (P<.05). The percentage of VC in EC samples was lower in the coronal and middle thirds than in the apical third (P<.05). EC, PUI and aPDT had significant effects on cell viability in intraradicular multispecies biofilm formed in situ when compared with untreated samples.

Resumo O presente estudo teve como objetivo avaliar a viabilidade bacteriana após o uso de diferentes protocolos de desinfecção em canais radiculares infectados com um biofilme multiespécies (MB) formado in situ. Raízes palatinas com canal único foram obtidas de molares superiores extraídos e esterilizadas antes de serem inseridas na boca. As raízes foram contaminadas com MB em um aparelho intraoral usado por dez voluntários. Todos os voluntários usaram seis raízes simultaneamente em dois dispositivos intrabucais por 21 dias. Uma raiz de cada voluntário foi atribuída a cada grupo (n=10): PUI - irrigação ultrassônica passiva; EC - Easy clean; XPF - XP-endo Finisher; aPDT - terapia fotodinâmica antimicrobiana; IC - irrigação convencional; e, NC - controle negativo. As amostras foram avaliadas em microscopia confocal de varredura a laser. A porcentagem de células viáveis (VC) foi calculada sobre a porcentagem total do biovolume de MB. Os dados foram analisados estatisticamente (α=5%). A viabilidade celular em todo o canal radicular ou em cada terço foi comparada entre os grupos (teste de Kruskal-Wallis, teste post-hoc de Dunn) e no mesmo grupo (teste de Friedman, teste post-hoc de Dunn). Os protocolos de desinfecção não foram significativamente diferentes entre si (P>0,05). Amostras dos grupos EC, PUI e aPDT apresentaram menor viabilidade celular do as do NC (P<0,05). No terço cervical das amostras do EC, XPF, PUI e aPDT, a porcentagem de biovolume de VC foi menor do que no NC (P<0,05). A porcentagem de VC nas amostras do EC foi menor nos terços cervical e médio do que no terço apical (P<0,05). EC, PUI e aPDT tiveram efeitos significativos na viabilidade celular do biofilme multiespécies intrarradicular formado in situ quando comparado com amostras não tratadas. Estudos clínicos devem investigar o papel da redução de cargas bacterianas viáveis no sistema de canais radiculares para o sucesso do tratamento endodôntico.

Tratamento de manifestação bucal exacerbada da doença de mão, pé e boca com apdt / Exacerbated oral manifestations of hand, foot and mouth disease: case report / Manifestaciones orales exacerbadas de la enfermedad de manos, pies y boca: reporte de un caso

Introdução: A doença da mão, pé e boca (DMPB) é uma infecção viral contagiosa que afeta principalmente crianças, mas também pode afetar adultos. É causada por diferentes tipos de enterovírus, sendo o CV-A16 e o EV-A71 os mais comuns. A transmissão ocorre pelo contato direto com fluidos corporais infectados ou por meio de objetos contaminados. Apresenta sintomas como febre, dor de garganta, falta de apetite e erupções cutâneas nas mãos, pés e boca. Embora a maioria dos casos seja leve e resolva- se espontaneamente, complicações graves, incluindo problemas neurológicos, podem ocorrer. O diagnóstico geralmente é clínico, com base nos sintomas e nas características das lesões. O tratamento é sintomático, com o uso de analgésicos e antitérmicos para aliviar a dor e a febre. No caso de lesões bucais graves a terapia fotodinâmica antimicrobiana (aPDT) em combinação com a fotobiomodulação com laser de baixa potência tem sido utilizada como uma abordagem promissora. A aPDT é capaz de eliminar microrganismos, incluindo vírus, independentemente de sua resistência aos antimicrobianos, e a fotobiomodulação auxilia na modulação da resposta inflamatória, alívio da dor e na cicatrização. Os lasers de baixa potência são a fonte de luz mais adequada para a fotoinativação viral, devido à sua interação precisa com o fotossensibilizante e a capacidade de fornecer a energia necessária para o efeito virucida. Metodologia: Relato de caso qualitativo e descritivo. Objetivo: Este relato de caso tem como objetivo descrever o tratamento de lesões bucais graves da DMPB combinando aPDT e fotobiomodulação com laser de baixa potência. Resultados: O tratamento mostrou resultados promissores no alívio dos sintomas e na melhora do quadro clínico. Conclusão: Mesmo em manifestações exacerbadas da doença de mão, pé e boca, podemos notar melhoras significativas nas lesões bucais após a aPDT com azul de metileno em combinação com a fotobiomodulação com laser de baixa potência.

Introduction: Hand, foot and mouth disease (HFMD) is a contagious viral infection that mainly affects children, but can also affect adults. It is caused by different types of enterovirus, with CV-A16 and EV-A71 being the most common. Transmission occurs through direct contact with infected body fluids or through contaminated objects. Symptoms include fever, sore throat, lack of appetite and rashes on the hands, feet and mouth. Although most cases are mild and resolve spontaneously, serious complications, including neurological problems, can occur. Diagnosis is usually clinical, based on the symptoms and characteristics of the lesions. Treatment is symptomatic, with the use of analgesics and antipyretics to relieve pain and fever. In the case of severe mouth lesions, antimicrobial photodynamic therapy (aPDT) in combination with low-power laser photobiomodulation has been used as a promising approach. aPDT is capable of eliminating microorganisms, including viruses, regardless of their resistance to antimicrobials, and photobiomodulation helps to modulate the inflammatory response, relieve pain and promote healing. Low-power lasers are the most suitable light source for viral photoinactivation, due to their precise interaction with the photosensitizer and their ability to provide the necessary energy for the virucidal effect. Methodology: Qualitative and descriptive case report. Objetive: This case report aims to describe the treatment of severe oral lesions of BPPD by combining aPDT and low-power laser photobiomodulation. Results: The treatment showed promising results in relieving symptoms and improving the clinical picture. Conclusion: Even in exacerbated manifestations of hand, foot and mouth disease, we can see significant improvements in mouth lesions after aPDT with methylene blue in combination with low-power laser photobiomodulation.

Introducción: La enfermedad de manos, pies y boca (EMPB) es una infección vírica contagiosa que afecta principalmente a los niños, aunque también puede afectar a los adultos. Está causada por diferentes tipos de enterovirus, siendo el CV-A16 y el EV-A71 los más comunes. La transmisión se produce por contacto directo con fluidos corporales infectados o a través de objetos contaminados. Los síntomas incluyen fiebre, dolor de garganta, falta de apetito y erupciones en manos, pies y boca. Aunque la mayoría de los casos son leves y se resuelven espontáneamente, pueden producirse complicaciones graves, incluidos problemas neurológicos. El diagnóstico suele ser clínico, basado en los síntomas y las características de las lesiones. El tratamiento es sintomático, con el uso de analgésicos y antipiréticos para aliviar el dolor y la fiebre. En el caso de lesiones bucales graves, la terapia fotodinámica antimicrobiana (aPDT) en combinación con la fotobiomodulación láser de baja potencia se ha utilizado como un enfoque prometedor. La aPDT es capaz de eliminar los microorganismos, incluidos los virus, independientemente de su resistencia a los antimicrobianos, y la fotobiomodulación ayuda a modular la respuesta inflamatoria, aliviar el dolor y favorecer la cicatrización. Los láseres de baja potencia son la fuente de luz más adecuada para la fotoinactivación viral, debido a su interacción precisa con el fotosensibilizador y a su capacidad para proporcionar la energía necesaria para el efecto virucida. Metodología: Caso clínico cualitativo y descriptivo. Objetivo: Este caso clínico pretende describir el tratamiento de lesiones orales severas de BPPD mediante la combinación de aPDT y fotobiomodulación con láser de baja potencia. Resultados: El tratamiento mostró resultados prometedores en el alivio de los síntomas y la mejora del cuadro clínico. Conclusión: Incluso en las manifestaciones exacerbadas de la enfermedad de manos, pies y boca, podemos observar mejoras significativas en las lesiones bucales tras la aPDT con azul de metileno en combinación con fotobiomodulación con láser de baja potencia.

Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn

Abstract Objective: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. Methods: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. Results: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). Conclusion: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

Láserterapia como coadyuvante del tratamiento de lesiones de furca grado II

Objetivo: evaluar la evidencia del láser como coadyuvante en el tratamiento quirúrgico de lesiones de furca grado II y reflejar la importancia clínica de los hallazgos para la toma de decisiones. Materiales y métodos: se realizó una búsqueda bibliográfica manual, se consultaron las siguientes bases de datos: PORTAL TIMBO FOCO, PUBMED, BVS, SciELO y GOOGLE SCHOOLAR. Esta búsqueda fue restringida a los últimos 15 años y los artículos seleccionados están en inglés. Resultados: Se seleccionaron 105 artículosque abordan la temática y se completó la búsqueda con el rastreo y la lectura de la bibliografía referenciada en esos artículos. Conclusiones: El láser de baja potencia tanto para la bioestimulación así como su efecto anti-inflamatorio, solo ha mostrado hasta ahora resultados positivos a corto plazo como coadyuvante del tratamiento periodontal regenerativo en lesiones de furca grado II. Sin embargo, sus resultados a largo plazo no son claros debido a la debilidad metodológica y al número insuficente de estudios existentes. Por otro lado, la terapia fotodinámica podría ser una alternativa para el control de pérdida ósea en lesiones de furca causadas por periodontitis. Por lo tanto, hacen falta más estudios para dilucidar la acción del la terapia fotodinámica y de la fotobiomodulación coadyuvantes del tratamiento de las lesiones de furca.

Objetivo: avaliar a evidência do laser como adjuvante no tratamento cirúrgico das lesões de furca grau II e refletir a importância clínica dos achados para a tomada de decisão. Materiais e métodos: foi realizada busca bibliográfica manual, consultadas as seguintes bases de dados: PORTAL TIMBO FOCO, PUBMED, BVS, SciELO e GOOGLE SCHOOL. Esta busca foi restrita aos últimos 15 anos e os artigos selecionados estão no idioma inglês. Resultados: foram selecionados 105 artigos que abordam o assunto e a busca foi concluída por meio de busca e leitura da bibliografia referenciada nesses artigos. Conclusões: O laser de baixa potência, tanto para a bioestimulação como para o seu efeito anti-inflamatório, apenas apresentou resultados positivos a curto prazo como adjuvante do tratamento periodontal regenerativo em lesões de furca grau II. No entanto, seus resultados a longo prazo não são claros devido a deficiências metodológicas e número insuficiente de estudos existentes. Por outro lado, a terapia fotodinâmica pode ser uma alternativa para controlar a perda óssea em lesões de furca causadas por periodontite. Portanto, mais estudos são necessários para elucidar a ação da Terapia Fotodinâmica e da fotobiomodulação como adjuvantes no tratamento da lesões de furca.

Objective: to evaluate the evidence of the efficacy of the adjuvant use of laser in the surgical treatment of grade II furcation lesions and to demonstrate the clinical importance of the findings for decision making. Materials and methods: a manual bibliographic search was carried out where the following databases were consulted: PORTAL TIMBO FOCO, PUBMED, SciELO, BVS and GOOGLE SCHOOL. This search was restricted to the last 15 years and the selected articles are in English. Results: 105 articles that addressed the subject were selected and the search was completed by searching and reading the referenced bibliography in those articles. Conclusions: Low-power laser, both for biostimulation and as an anti-inflammatory has so far only shown positive short-term results as an adjunct to regenerative periodontal treatment in grade II furcation lesions. However, its long-term results are not clear due to methodological weaknesses and the insufficient number of existing studies. On the other hand, photodynamic therapy could be an alternative to control bone loss in furcation lesions caused by periodontitis. However, more studies are needed to elucidate the action of photodynamic therapy and photobiomodulation as adjuvants in the treatment of furcation lesions.

Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Abstract We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.

Manifestação atípica do herpes zóster em boca: relato de caso / Atypical manifestation of herpes zoster in the mouth: case report / Manifestación atípica de herpes zoster en boca: reporte de caso

O herpes-zóster é uma infecção viral causada pela reativação do vírus da varicela-zóster (VZV) sendo os ramos do nervo trigêmeo afetados em até 20% dos casos. Apresenta-se comumente com dor em queimação e caracteristicamente, o zoster se manifesta como uma erupção vesicular unilateral que aparece na face, cabeça, tronco e até mesmo nas extremidades, variando de lesão leve e de rápida cicatrização à lesões graves e extensas com duração de semanas. Embora se reconheça que o zoster pode ocorrer sem exantema, classicamente apresenta-se como dermátomo unilateral, doloroso e/ou pruriginoso. A terapia fotodinâmica antimicrobiana (aPDT) tem sido indicada como uma modalidade promissora no tratamento de potenciais lesões infecciosas. Neste trabalho será relatado o caso clínico de um paciente diagnosticado com herpes zóster com manifestação atípica e que recebeu tratamento medicamentoso convencional associado à aPDT.

Herpes zoster is a viral infection caused by the reactivation of the varicella zoster virus (VZV), with the branches of the trigeminal nerve affected in up to 20% of cases. It commonly presents with burning pain and characteristically, zoster manifests as a unilateral vesicular eruption appearing on the face, head, trunk, and even the extremities, ranging from a mild, rapidly healing lesion to severe, extensive lesions lasting up to weeks. Although it is recognized that zoster can occur without rash, it classically presents as a unilateral, painful and/or pruritic dermatome. Antimicrobial photodynamic therapy (aPDT) has been indicated as a promising modality in the treatment of potential infectious lesions. In this work, the clinical case of a patient diagnosed with herpes zoster with atypical manifestation and who received conventional drug treatment associated with aPDT will be reported.

El herpes zóster es una infección vírica provocada por la reactivación del virus de la varicela zóster (VZV), con afectación de las ramas del nervio trigémino hasta en un 20% de los casos. Comúnmente se presenta con dolor ardiente y característicamente, el zoster se manifiesta como una erupción vesicular unilateral que aparece en la cara, la cabeza, el tronco e incluso las extremidades, que van desde una lesión leve que cura rápidamente hasta lesiones graves y extensas que duran semanas. Aunque se reconoce que el herpes zoster puede ocurrir sin exantema, clásicamente se presenta como un dermatoma unilateral, doloroso y/o pruriginoso. La terapia fotodinámica antimicrobiana (aPDT) se ha indicado como una modalidad prometedora en el tratamiento de posibles lesiones infecciosas. En este trabajo se reportará el caso clínico de un paciente diagnosticado de herpes zoster con manifestación atípica y que recibió tratamiento farmacológico convencional asociado a TFPa.

Development of exosome membrane materials-fused microbubbles for enhanced stability and efficient drug delivery of ultrasound contrast agent

Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

Effects of different debridement methods on titanium surfaces in vitro / 口腔疾病防治

Objective @#To investigate the effect of different decontamination methods, including photodynamic therapy, sandblasting and titanium curette, on titanium surface morphology and bacterial adhesion for the treatment of peri-implant disease. @*Methods@#Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) were inoculated on the surface of polished titanium specimens, and titanium specimen surfaces were treated with different decontamination methods after incubation. The titanium specimens were divided into a no-treatment control group, photodynamic group, sandblasting group and titanium curette group according to different decontamination methods. The changes in titanium surface roughness were observed by atomic force microscopy (AFM), and the remaining bacteria on the titanium surface were observed by scanning electron microscopy (SEM) and live/dead bacteria staining tests. After reinoculation of Pg and Fn, bacterial readhesion was observed on the surface of decontaminated titanium specimens. @*Results @#The AFM results showed that the surface roughness of the titanium curette group was significantly higher than that of the no-treatment control group, photodynamic group and sandblasting group (P<0.05), and there was no statistically significant difference between the no-treatment control group, photodynamic group and sandblasting group (P>0.05). The results of contact angle measurement showed that the surface contact angle of each treatment group was smaller than that of the no-treatment control group (P<0.05). The SEM results obtained after the titanium specimen surface was decontaminated showed that the number of bacteria on the no-treatment control group surface was higher and the bacteria were relatively concentrated. The bacteria on the surface of the photodynamic group, sandblasting group and titanium curette group were scattered and distributed in small numbers, and most bacteria on the surface of the photodynamic group were ruptured. The results of the live/dead bacteria staining experiment showed that the percentage of dead bacteria on the surface of the photodynamic group was significantly higher than that of the no-treatment control group, sandblasting group and titanium curette group (P<0.05). The remaining bacteria on the surface of the sandblasting group and titanium curette groups were mainly live bacteria. The remaining bacterial adhesion on the surface was significantly reduced for the sandblasting group compared to the no-treatment control group and the photodynamic and titanium curette groups (P<0.05). SEM and live/dead bacteria staining results of bacterial readhesion on the surface of titanium specimens showed that there was an aggregation of Pg on the surface of the titanium curette group, and its surface bacterial adhesion was significantly higher than that of the no-treatment control group, photodynamic group and sandblasting group. @*Conclusion @#In mechanical decontamination, sandblasting machines are a better option than photodynamic therapy and titanium curettes; however, sandblasting does not remove all bacterial contamination. For sterilization, photodynamic therapy is more effective than sandblasting and titanium curettes. A combination of sandblasting and photodynamic therapy methods for the treatment of peri-implant disease may be considered in clinical practice.

Research progress of exosome delivery vehicles in tumor phototherapy / 药学学报

Exosome is a self-secreted phospholipid bilayer nanovesicles, and has shown great potential in drug delivery field due to the important advantages of low immunogenicity and homologous targeting. Phototherapy, mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT), utilize light to activate photoactive drug for tumor cell killing. The advanced therapeutic strategy shows low toxic side-effect and non-invasion precise advantages, and thus has made great progress in tumor treatment over the past few years. Therefore, using exosomes as a drug delivery system to deliver phototherapeutic agents can improve therapeutic performances with a reduced side-effect, and further enhance their application potential for clinical tumor therapy. This review focus on the rising cross-subjects field involving exosomes and phototherapy, and mainly introduce the research progress and relative case of exosomes-based delivery system for cancer phototherapy. Additionally, the advantages and challenges of exosome-based phototherapy are also discussed and proposed.

Research advances of focal therapy for prostate cancer / 现代泌尿外科杂志

Prostate cancer is now the second most common malignancy in men worldwide, with an increasing incidence in China. Most prostate cancer patients receive whole-gland therapy after diagnosis, but patients with localized prostate cancer may not benefit from the treatment due to side effects. With the development of imaging technology and the theory of "index lesion," focal therapy has been greatly developed, which includs high intensity focused ultrasound, focal laser ablation, cryotherapy, irreversible electroporation and photodynamic therapy. This study reviews the clinical trials in recent years and reveals that high intensity focused ultrasound and focal laser ablation have better failure-free survival and postoperative functional control compared with other focal therapy techniques.

Clinical application progress on the diode laser in nonsurgical periodontal treatment / 口腔疾病防治

@#Chronic periodontitis is a chronic inflammatory disease caused by plaque microorganisms, and removal of plaque and calculus is the gold standard for nonsurgical periodontal treatment. However, complete debridement is difficult, especially in some complex anatomical sites. Excessive scaling may result in the loss of healthy cementum and lead to dental hypersensitivity. Studies have shown that a diode laser can exhibit the best performance in an environment with blood because its wavelengths (630-1 064 nm) are close to the absorption peaks of heme and melanin and they have broad application prospects in the oral field. In nonsurgical periodontal treatment, diode lasers have three treatment modes: soft diode laser, antimicrobial photodynamic therapy and low-level laser therapy, which can be used alone or in combination. Although diode lasers cannot replace mechanical treatment to remove calculus, they can remove infected periodontal pocket epithelium, change the microcirculation to promote wound healing, reduce bleeding and relieve pain through photothermal effects and biological stimulation. The effect of diode laser treatment depends on the treatment dose. It is necessary to precisely control the output intensity and control the irradiation time to avoid thermal damage to the tissue. In the future, extensive research at the molecular level is needed to reveal the tissue response. At the same time, more high-quality, large-sample randomized controlled trials are needed to standardize the use of lasers for different stages and grades of periodontitis.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022) / 中国医学科学杂志(英文版)

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Current status and prospect of composite nano-phototherapy agents in the phototherapy for breast cancer treatment / 中国药房

As an adjuvant alternative therapy， phototherapy is widely used for early diagnosis and late treatment of breast cancer due to its non-invasive treatment characteristics. But the application of phototherapeutic agents has been limited in the clinic due to poor hydrophobicity and tissue targeting， low photostability， and obvious toxic side effects in vivo. With the development of nanotechnology， new composite nano-phototherapy agents have emerged. This paper summarizes the latest developments and findings of new composite nano-phototherapy agents for phototherapy in the field of breast cancer treatment in the past 5 years. With the development of multifunctional nanomaterials in the field of breast cancer imaging diagnosis and treatment， the modified phototherapy agent achieved further development respectively from improving light response to improve the light thermal conversion or increasing the generation of reactive oxygen species， targeting tumor microenvironment， immune cells and cancer cell surface receptors to achieve drug controllable response release， using biomimetic materials and endogenous substances to improve biocompatibility. Although phototherapeutic agents exhibit high cell-killing rates in the treatment of metastatic breast cancer models and effectively inhibit their recurrence and metastasis， problems remain regarding the safety and compatibility of synergistic therapy. Future studies can not only improve the existing effects of phototherapeutic agents， but also develop oral drugs with more convenient routes based on immunotherapy to amplify the immune response and resist breast cancer through multiple routes.