Transcriptomic analysis of mechanism of melanoma cell death induced by photothermal therapy.

Melanoma is a malignancy with poor prognosis. Its incidence rate has been on the rise and it poses high health and economic challenges to different populations. Photothermal therapy (PTT) served as an effective local therapy in treating various tumors, particularly cutaneous carcinoma like melanoma. To fully understand the mechanisms of tumor cell death induced by PTT, we investigated gene expression and immune cells compositions of B16-F10 tumors after PTT treatment. A total of 256 differentially expressed genes (DEGs) were identified, with 215 being downregulated and 41 upregulated by PTT. Functional annotation showed that most DEGs involved in immune response and inflammatory response. Immune cells compositions inference revealed changes in many immune cells including regulatory T cells, M2 macrophage and B cells after PTT treatment. Our results help delineate the mechanism of cell death at the transcriptional level triggered by non-invasive PTT treatment of melanoma without exogenous light absorbing agents.

Photothermal therapy enhanced the effectiveness of imiquimod against refractory cutaneous warts through boosting immune responses.

Refractory cutaneous warts are difficult to eliminate. In situ photo-immunotherapy (ISPI) is an innovative treatment concept combining local photothermal therapy (PTT) and topical immunotherapy using imiquimod. To compare the efficacy of ISPI vs topical imiquimod alone, a prospective randomized controlled trial was performed with patients suffering from refractory cutaneous warts. In both groups, approximately 50% of the skin surface containing warts was treated for 6 weeks. On the basis of topical imiquimod, ISPI includes an additional 808 nm laser irradiation. Treatment response, temperatures during irradiation and histopathologic examination were evaluated. The complete response rate in the ISPI-group (22/36, 61.1%) was significantly higher than in the imiquimod alone group (11/34, 32.4%). In the ISPI-group, the mean maximum temperature was 44.5 ± 5.1°C, and obvious lymphocytic infiltration was found in the perivasculature of the dermis. There was no recurrence or worsening in both groups during the 12-month follow-up. No obvious adverse reaction was observed. This study demonstrates that ISPI can be used as an effective and safe treatment modality for refractory cutaneous warts.

Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumour immunogenicity.

BACKGROUND: Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumours by damaging tumour cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumour immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC). METHODS: The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC. RESULTS: The temperature in the range of 45-50 °C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumours and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (p < 0.05). The patient with cSCC treated by laser immunotherapy experienced a significant tumour reduction after laser immunotherapy increased the amounts of infiltrating lymphocytes in the tumour. No obviously adverse effect was observed in the mice experiment or in the clinical application. CONCLUSIONS: Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.

A novel cosmetic and clinically practicable laser immunotherapy for facial verruca plana: Intense pulsed light combined with BCG-PSN.

BACKGROUND: There is no standard method to remove facial verruca plana and achieve better cosmetic effects. The present study is the first study to use intense pulsed light (IPL) as photothermal therapy (PTT) combined with intra-gluteal injection of bacillus calmette-guerin polysaccharide nucleic acid (BCG-PSN), which function as immunotherapy, contracting a new type of clinically available laser immunotherapy (LIT) for the treatment of facial verruca plana. The aim of this study was to evaluate the efficacy, cosmetic outcome, and adverse reactions of IPL combined with BCG-PSN for facial verruca plana. METHODS: Twenty-three patients with facial verruca plana were treated with IPL (560-nm filter, 15-17 J/cm2) and all patients were given intra-gluteal injections of BCG-PSN twice a week for 8 weeks combined with IPL once a month in two times. The clinical responses, recurrences, adverse reactions, and rejuvenation outcomes were evaluated. RESULTS: A complete and excellent response was noted in 17 patients (74%). Of the 676 treated warts, 548 were eradicated and the overall clearance rate was 81%. No patient relapsed during the 20-week follow-up. No obvious adverse reactions was observed. Almost all patients showed an improvement in skin texture after IPL treatment CONCLUSION: We conclude that a novel LIT based on BCG-PSN and IPL for the treatment of facial verruca plana proved to be a well-tolerated and effective treatment modality. This novel LIT can clear skin lesions and achieve a very good cosmetic effect.

Successful treatment of Rosai-Dorfman disease using in situ photoimmunotherapy.

Rosai-Dorfman disease is difficult to cure. In situ photoimmunotherapy combines local photothermal therapy with immunoadjuvant. In the present case report, a 39-year-old Chinese man with Rosai-Dorfman disease lesions below the left nostril and left preauricular region was treated with in situ photoimmunotherapy. The patient was treated with daily application of topical imiquimod (5%) and laser irradiations every 2 weeks for 8 weeks. After three cycles of treatment, the lesions improved markedly without adverse effects. Our results showed that in situ photoimmunotherapy can be used as an effective treatment for Rosai-Dorfman disease.

Albumin-Bioinspired Gd:CuS Nanotheranostic Agent for In Vivo Photoacoustic/Magnetic Resonance Imaging-Guided Tumor-Targeted Photothermal Therapy.

Photothermal therapy (PTT) is attracting increasing interest and becoming more widely used for skin cancer therapy in the clinic, as a result of its noninvasiveness and low systemic adverse effects. However, there is an urgent need to develop biocompatible PTT agents, which enable accurate imaging, monitoring, and diagnosis. Herein, a biocompatible Gd-integrated CuS nanotheranostic agent (Gd:CuS@BSA) was synthesized via a facile and environmentally friendly biomimetic strategy, using bovine serum albumin (BSA) as a biotemplate at physiological temperature. The as-prepared Gd:CuS@BSA nanoparticles (NPs) with ultrasmall sizes (ca. 9 nm) exhibited high photothermal conversion efficiency and good photostability under near-infrared (NIR) laser irradiation. With doped Gd species and strong tunable NIR absorbance, Gd:CuS@BSA NPs demonstrate prominent tumor-contrasted imaging performance both on the photoacoustic and magnetic resonance imaging modalities. The subsequent Gd:CuS@BSA-mediated PTT result shows high therapy efficacy as a result of their potent NIR absorption and high photothermal conversion efficiency. The immune response triggered by Gd:CuS@BSA-mediated PTT is preliminarily explored. In addition, toxicity studies in vitro and in vivo verify that Gd:CuS@BSA NPs qualify as biocompatible agents. A biodistribution study demonstrated that the NPs can undergo hepatic clearance from the body. This study highlights the practicality and versatility of albumin-mediated biomimetic mineralization of a nanotheranostic agent and also suggests that bioinspired Gd:CuS@BSA NPs possess promising imaging guidance and effective tumor ablation properties, with high spatial resolution and deep tissue penetration.

In situ photoimmunotherapy for cutaneous granuloma caused by itraconazole-resistant Candida guilliermondii.

Cutaneous granulomas caused by Candida guilliermondii are difficult to cure. In situ photoimmunotherapy (ISPI) is a novel method composed of local photothermal therapy and immunoadjuvant. In this study, ISPI was used the first time clinically for cutaneous granuloma caused by itraconazole-resistant C.guilliermondii. A 10-week cycle of ISPI was composed of (1) 5% imiquimod applied topically every other day and (2) irradiation of lesions with an 808-nm diode laser at Days 14, 28, 42, and 56. Here we report our first case. A patient was treated with ISPI for four cycles. After the treatment, the lesions were eliminated without recurrence during a 12-month follow-up. Our results demonstrate that ISPI can be used as an effective treatment modality for cutaneous fungal granuloma.