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Robust Photodynamic Therapy Using 5-ALA-Incorporated Nanocomplexes Cures Metastatic Melanoma through Priming of CD4 <sup>+</sup> CD8 <sup>+</sup> Double Positive T Cells
摘要： Advanced melanoma can rarely be cured. Photodynamic therapy (PDT) readily eradicates the primary melanoma but has limited ability to destroy the spreading tumor cells unless supported by other combinative interventions to augment systemic antitumor immunity. Based on the previously synthesized penetration-enhancing biomaterials, a topically administered nanoformulation is developed, which profoundly assists 5-aminolevulinic acid (5-ALA) in circumventing skin barrier to be selectively delivered to tumor cells. After endocytosis, accumulated 5-ALA is efficiently metabolized to a photosensitizer protoporphyrin IX (PpIX) which stimulates a large production of cytotoxic reactive oxygen species (ROS) under illumination. Accompanied by the robust inflammatory responses followed by primary tumor destruction, CD4+CD8+ double positive T cells are highly boosted to harness host immunity to purge metastases in lymphoid organs. Compared with dacarbazine and programmed death 1 (PD-1) antibody, this treatment in advanced melanoma murine models, achieves a striking curable rate of 90% without melanoma prognostic markers LDH and S-100B detection, followed by a relapse-free survival rate of 83.33% in 300 days. Moreover, the cured mice’s immune system function recovers to an extent similar to healthy mice without prolonged or exaggerated inflammation. This study using the synergistic biomaterials approach may thus render 5-ALA-mediated PDT a potentially curative therapy for advanced melanoma in clinic.
关键词： advanced melanoma,CD4+CD8+ double positive cells,relapse-free survival,5-aminolevulinic acid,cure
更新于2025-11-25 10:30:42
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Photo-Modification of Melanin by a Mid-Infrared Free-Electron Laser
摘要： Melanin is rigidly constructed by several nitrogen-containing aromatic rings, and its excess accumulation in skin tissue is closely associated with melanosis. Although visible lasers (wavelength: 600–1000 nm) are conventionally used for the photo-thermolysis of melanocyte, several pigmented nevi are difficult to be treated. Here, we propose an alternate method for targeting the molecular structure of melanin using an infrared free electron laser (FEL) tuned to 5.8 μm that corresponds to the stretching vibrational mode of carboxylate group. A drastic morphological change on the black-colored surface of melanin powder were observed after the pulse irradiation with a power of 500 mJ/cm2, and the minimum irradiation time for damage to the morphology was 1.4 seconds. Analyses by mass spectroscopy, infrared spectroscopy, and 13C-nuclear magnetic resonance implied that a pyrrole group was removed by the FEL irradiation. In addition, the FEL irradiation dispersed almost all of the melanoma cells from a culture solution without any influence on other ingredients in the medium, and one-cell analysis by infrared microscopy showed that the structure of melanoma could be substantially damaged by the irradiation. This study proposes the potency of intense mid-infrared laser as novel alternative way to reduce melanin.
关键词： Infrared free electron laser,Melanoma,Vibrational mode,Melanin,Photo-modification
更新于2025-11-21 11:03:13
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CD146-Targeted Multimodal Image-Guided Photoimmunotherapy of Melanoma
摘要： For melanoma resistant to molecularly targeted therapy and immunotherapy, new treatment strategies are urgently needed. A molecularly targeted theranostic pair may thus be of importance, where the diagnostic probe facilitates patient stratification and the therapeutic companion treats the selected cases. For this purpose, flow cytometry is used to assess the CD146 level in melanoma cells. Based on YY146, a CD146-specific monoclonal antibody, an imaging probe 89Zr-Df-YY146 is synthesized and its diagnostic performance is evaluated by positron emission tomography (PET) imaging. Furthermore, a photoimmunotherapy (PIT) agent IR700-YY146 is developed and the therapeutic effect of IR700-YY146 PIT is assessed comprehensively. CD146 is highly expressed in A375 and SK-MEL-5 cells. 89Zr-Df-YY146 PET readily detects CD146-positive A375 melanomas. Tumor accumulation of 89Zr-Df-YY146 peaks at 72 h with an uptake value of 26.48 ± 3.28%ID g?1, whereas the highest uptake of the nonspecific 89Zr-Df-IgG is 4.80 ± 1.75%ID g?1. More importantly, IR700-YY146 PIT effectively inhibits the growth of A375 tumors, owing to production of reactive oxygen species, decreased glucose metabolism, and reduced expression of CD146. To conclude, 89Zr-Df-YY146 and IR700-YY146 are a promising theranostic pair with the former revealing CD146 expression in melanoma as a PET probe and the latter specifically treating CD146-positive melanoma as an effective PIT agent.
关键词： YY146,immunoPET,melanoma,photoimmunotherapy,theranostics
更新于2025-11-19 16:56:35
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Intratumorally Injected Photothermal Agent-Loaded Photodynamic Nanocarriers for Ablation of Orthotopic Melanoma and Breast Cancer
摘要： Traditional chemotherapy of cancers may lead to serious adverse reactions due to little drug distribution in tumors. Here, a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) was used for local treatment of orthotopic melanoma and breast cancer via intratumoral (i.t.) injection of photothermal agent-loaded photodynamic nanocarriers. A hydrophobic derivative of indocyanine green, DCC, was synthesized and entrapped into a pH-sensitive photosensitizer-core copolymer, PDCZP, to form DCC@PDCZP. The nanocarriers showed remarkable fluorescence, high singlet oxygen quantum yields, and strong photothermal effect. Flow cytometry suggested that the nanocarriers were efficiently internalized by cancer cells. Near infrared thermal imaging and fluorescence self-imaging showed that the i.t. injected DCC@PDCZP mainly remained in the tumors but the intravenous (i.v.) nanocarriers were distributed a little. One i.t. injection of DCC@PDCZP was enough to ablate the orthotopic B16-F10 and 4T1 mouse tumors under 830 nm and 660 nm irradiation at 4 hours post-injection. More importantly, no local recurrences were found though scabs were formed at 9 days post-treatment. The major anticancer mechanisms included improvement of cancer cell necrosis due to hyperthermia, inhibition of neovascularization, and enhancement of cell apoptosis. The i.t. injection of PTT/PDT nanoformulations is thus a promising local treatment of superficial tumors.
关键词： zinc phthalocyanine,intratumoral injection,melanoma,indocyanine green,breast cancer,photodynamic therapy,photothermal therapy
更新于2025-09-23 15:23:52
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Reflectance confocal microscopy margin mapping and monitoring of an amelanotic melanoma <i>in situ</i> of the ear
摘要： In situ amelanotic melanoma represents a diagnostic challenge for clinicians. Poor demarcation of these lesions often results in repeated therapeutic intervention until appropriate clearance has been achieved. Reflectance confocal microscopy (RCM) is a noninvasive bedside imaging modality which allows real-time visualisation, to a near-histological level, of the epidermis and reticular dermis. We present a case of an amelanotic melanoma in situ in which reflectance confocal microscopy margin mapping allowed for demarcation of the melanocytic proliferation and targeted therapeutic intervention with topical imiquimod. Reflectance confocal microscopy was further utilised for noninvasive assessment of therapeutic response.
关键词： margin mapping,reflectance confocal microscopy,amelanotic melanoma
更新于2025-09-23 15:23:52
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Portable spectroscopic system for <i>in vivo</i> skin neoplasms diagnostics by Raman and autofluorescence analysis
摘要： This paper studies the applicability of a portable cost-effective spectroscopic system for the optical screening of skin tumors. In vivo studies of Raman scattering and autofluorescence of skin tumors with the 785 nm excitation laser in the near infrared region included malignant melanoma, basal cell carcinoma, and various types of benign neoplasms. The efficiency of the portable system was evaluated by comparison with a highly sensitive spectroscopic system and with the diagnosis accuracy of a human oncologist. Partial least square analysis of Raman and autofluorescence spectra was performed; specificity and sensitivity of various skin oncological pathologies detection varied from 78.9% to 100%. 100% accuracy of benign and malignant skin tumors differentiation is possible only with a combined analysis of Raman and autofluorescence signals.
关键词： autofluorescence,optical biopsy,portable spectroscopic equipment,skin neoplasms,melanoma,partial least square analysis,Raman spectroscopy,malignancy
更新于2025-09-23 15:23:52
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[IEEE 2018 International Conference on Control, Power, Communication and Computing Technologies (ICCPCCT) - Kannur (2018.3.23-2018.3.24)] 2018 International Conference on Control, Power, Communication and Computing Technologies (ICCPCCT) - Identification of Melanoma in Dermoscopy Images Using Image Processing Algorithms
摘要： Skin cancer is the most common of all human cancers and is always misunderstood with other kind of skin diseases, so accurate early detection of skin cancer is essential. The main objective of this paper is to segment the lesion and identify melanoma from dermoscopy images. A total of 170 dermoscopy images are used in this research. Firstly, the input images are enhanced for better processing then, the lesion portion is segmented from the enhanced image by two methods 1.Otsu thresholding 2.Morphological operations. The descriptive features are extracted from the segmented lesion. The extracted feature values are used to compute the Total Dermatascopy Score (TDS), which is used to find the presence or absence of melanoma in dermoscopy images. Classification accuracy is calculated to assess the performance of the proposed algorithm.
关键词： Dermoscopy,Segmentation,Total Dermatoscopy Score(TDS),Feature Extraction,Melanoma,Skin cancer
更新于2025-09-23 15:22:29
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[IEEE 2018 International Conference on Intelligent Informatics and Biomedical Sciences (ICIIBMS) - Bangkok (2018.10.21-2018.10.24)] 2018 International Conference on Intelligent Informatics and Biomedical Sciences (ICIIBMS) - Computational Study of Frozen Tissue Melanoma Imagining at Terahertz Frequencies
摘要： Terahertz radiation is highly absorbed by liquid water, with less than 0.0001% of the signal surviving to a depth of 1.0 millimeter at 0.45 terahertz, limiting the potential for imaging of human tissues. On the other hand, 90% of the terahertz signal survives in ice in the 0.1 to 1.0 terahertz band, opening the possibility of in-vivo imaging of skin lesions, particularly melanomas, to a depth of 5.0 millimeters by first freezing the skin in situ. Computational modelling of THz-frozen skin imaging indicates that contrast exists to differentiate melanomas from normal frozen skin on the basis of water content alone. If the melanin content of melanomas is a significant absorber of terahertz radiation, then melanin becomes the main contrast element. The modelling results justify the further exploration of the imaging technique with the study of ex-vivo frozen melanoma samples before progressing to in-vivo clinical trials.
关键词： terahertz,melanoma,skin,freezing,imaging
更新于2025-09-23 15:22:29
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Evaluation of [ <sup>11</sup> C]NMS-E973 as a PET tracer for <i>in vivo</i> visualisation of HSP90
摘要： Heat shock protein 90 is an ATP-dependent molecular chaperone important for folding, maturation and clearance of aberrantly expressed proteins and is abundantly expressed (1-2% of all proteins) in the cytosol of all normal cells. In some tumour cells, however, strong expression of HSP90 is also observed on the cell membrane and in the extracellular matrix and the affinity of tumoural HSP90 for ATP domain inhibitors was reported to increase over 100-fold compared to that of HSP90 in normal cells. Here, we explore [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90 and as a potential tool for in vivo quantification of occupancy of HSP90 inhibitors. Methods: HSP90 expression was biochemically characterized in a panel of established cell lines including the melanoma line B16.F10. B16.F10 melanoma xenograft tumour tissue was compared to non-malignant mouse tissue. NMS-E973 was tested in vitro for HSP90 inhibitory activity in several tumour cell lines. HSP90-specific binding of [11C]NMS-E973 was evaluated in B16.F10 melanoma cells and B16.F10 melanoma, prostate cancer LNCaP and PC3, SKOV-3 xenograft tumour slices and in vivo in a B16.F10 melanoma mouse model. Results: Strong intracellular upregulation and abundant membrane localisation of HSP90 was observed in the different tumour cell lines, in the B16.F10 tumour cell line and in B16.F10 xenograft tumours compared to non-malignant tissue. NMS-E973 showed HSP90-specific inhibition and reduced proliferation of cells. [11C]NMS-E973 showed strong binding to B16.F10 melanoma cells, which was inhibited by 200 μM of PU-H71, a non-structurally related HSP90 inhibitor. HSP90-specific binding was observed by in vitro autoradiography of murine B16.F10 melanoma, LNCaP and PC3 prostate cancer and SKOV-3 ovary carcinoma tissue slices. Further, B16.F10 melanoma-inoculated mice were subjected to a μPET study, where the tracer showed fast and persistent tumour uptake. Pretreatment of B16.F10 melanoma mice with PU-H71 or Ganetespib (50 mg/kg) completely blocked tumour accumulation of [11C]NMS-E973 and confirmed in vivo HSP90 binding specificity. HSP90-specific binding of [11C]NMS-E973 was observed in blood, lungs and spleen of tumour-bearing animals but not in control animals. Conclusion: [11C]NMS-E973 is a PET tracer for in vivo visualisation of tumour HSP90 expression and can potentially be used for quantification of HSP90 occupancy. Further translational evaluation of [11C]NMS-E973 is warranted.
关键词： HSP90,melanoma,PET imaging,carbon-11,NMS-E973
更新于2025-09-23 15:22:29
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An Update on Topical Photodynamic Therapy for Clinical Dermatologists
摘要： Photodynamic therapy (PDT) involves the application of a topical photosensitizer, irradiation with light, and oxygen to produce cytotoxic reactive oxygen species that selectively destroy damaged cells while leaving normal skin intact. Topical PDT is a commonly used treatment for non-melanoma skin cancers (NMSCs) due to its excellent clearance rate and cosmetic outcomes. However, PDT is emerging as an off-label treatment modality for many dermatological conditions. A literature review using MEDLINE was performed to identify randomized controlled trials conducted for currently approved and off-label clinical indications and photosensitizers for PDT between 2012 and 2018. The photosensitizer indole-3 acetic acid reduces the incubation time (<30 minutes), avoids the need for photoprotection after irradiation, and inflicts minimal pain. Cyclic PDT in individuals with evidence of field cancerization delays the mean time of actinic keratosis appearance and reduces the total number of new actinic keratoses. Substantial evidence exists outlining the utility of PDT in photorejuvenation due to its ability to improve skin texture, wrinkles, and firmness. The addition of microdermabrasion, microneedling, curettage, or various lasers improves clinical efficacy and cosmetic outcomes. PDT applications are expanding rapidly. Clinicians must stay up to date regarding the efficacy and safety of PDT applications.
关键词： non-melanoma skin cancer,daylight PDT,dermatology,PDT,actinic keratosis,photodynamic therapy
更新于2025-09-23 15:22:29