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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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Photodynamic Therapy in the Treatment of Bladder Cancer: Past Challenges and Current Innovations
摘要： There are limited treatment options for patients with recurrent non-muscle-invasive bladder cancer. In this report, we will talk about the history of photodynamic therapy; although it showed encouraging therapeutic results, it was largely abandoned due to toxicity or bystander effects on normal cells. Monoclonal antibody-conjugates represent an emerging therapeutic approach for malignancies that improves upon tumor specificity. The use of a monoclonal antibody-photosensitizer conjugate is a more selective method of delivering light therapy and has been termed 'photoimmunotherapy', which we will discuss in the last part of this report.
关键词： Hematoporphyrin,Urothelial cancer,Hexaminolevulinic acid,Photoimmunotherapy,PIT,BCG-refractory NMIBC,PDT,Bladder cancer,5-Aminolevulinic acid,Photodynamic therapy
更新于2025-09-23 15:23:52
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5-aminolevulinic acid induced protoporphyrin IX (ALA-PpIX) fluorescence guidance in meningioma surgery
摘要： Introduction 5-aminolevulinic acid induced protoporphyrin IX (5-ALA-PpIX) fluorescence guidance has emerged as a valuable surgical adjunct for resection of intracranial tumors. Methods Here we present a focused review on 5-ALA-PpIX fluorescence guidance for meningiomas. Results We discuss the clinical studies and specific applications to date as well as the two main intraoperative fluorescence technologies applied to meningiomas. Conclusions The use of 5-ALA-PpIX in meningiomas holds promising potential so neurosurgeons can improve surgical outcomes for patients with meningiomas as well as be pioneers in developing improved fluorescence imaging technologies.
关键词： Meningioma,Quantitative fluorescence,5-Aminolevulinic acid,Fluorescence-guided surgery,Protoporphyrin IX,Spectroscopy
更新于2025-09-23 15:23:52
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Plum-blossom needle assisted photodynamic therapy: The therapy option for the treatment of oral potentially malignant disorder in the elderly
摘要： Oral leukoplakia (OLK) is one of the most common oral potentially malignant disorders (OPMD) with complex causes, a long disease course and a high tendency for recrudescence. Although a variety of methods exist for treating this disease, canceration rates remain high. Herein, we described a case of 72-year-old male patient with OLK of the palatine mucous membrane who had achieved complete remission after being treated with five sessions of plum-blossom needle (PBN) assisted 5-aminolevulinic acid-photodynamic therapy (ALA-PDT). The patient had since been subsequently placed under close observation (>12 mo). To date, there has been no recurrence. PBN assisted PDT might be suitable for the treatment of OPMDs in patients presenting with epithelial hyperkeratosis.
关键词： Plum-blossom needle,Oral potentially malignant disorders,Photodynamic therapy,Aminolevulinic acid,Hyperkeratosis,Oral leukoplakia
更新于2025-09-23 15:23:52
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Hyperbaric oxygen combined with 5-aminolevulinic acid photodynamic therapy inhibited human squamous cell proliferation
摘要： The photodynamic therapy (PDT) depends on the presence of molecular oxygen. Thus, the efficiency of PDT is limited in anoxic regions of tumor tissue and vascular shutdown. It is reported the use of hyperbaric oxygen (HBO) may enhance the efficiency of PDT. However, there are rarely studies about utilizing HBO plus PDT for treatment with human squamous cell carcinoma (SCC). Therefore, this study aimed to investigate and compare the therapeutic effect of combined therapy and PDT alone treatment. Multiple cellular and molecular biology techniques were used in the current study such as CCK-8, western blotting, flow cytometry, MDC staining and immunofluorescence assay. The results of combination index indicated that HBO combination with PDT synergistically inhibited A431 cells proliferation in vitro. In addition, we found that HBO significantly enhanced PDT-induced cell apoptosis via increasing the active caspase-3, active caspase-9, Apaf-1 and Bax levels and down-regulating Bcl-2. Meanwhile, the result of MDC and immunofluorescence assay confirmed that HBO increased PDT-induced autophagosome formation in A431 cells. Interestingly, autophagy inhibitor 3-methyladenine (3-MA) further increased combination-induced cell apoptosis by increasing the levels of active-caspase 9 and Apaf-1. Our results showed that HBO combined with PDT markedly induced A431 cells apoptosis and autophagy. Nevertheless, autophagy play a pro-survival role against apoptosis. Thus, HBO combination with PDT may constitute a promising approach to treat human squamous cell carcinoma in the future.
关键词： human squamous cell carcinoma,5-aminolevulinic acid photodynamic therapy,apoptosis,autophagy,hyperbaric oxygen
更新于2025-09-23 15:23:52
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Cancer Selective Turn-on Fluorescence Imaging Using a Biopolymeric Nanocarrier
摘要： Most nanoparticle-based bioresearch for clinical applications is unable to overcome the clinical barriers of efficacy (e.g., sensitivity and selectivity), safety for human use, and mass-production processes. Here, we proposed a promising concept of using a biocompatible nanocarrier that delivers natural fluorescent precursors into cancerous cells. The nanocarrier is a biopolymeric nanoparticle that can be easily loaded with fluorescent precursors to form a fluorescent moiety via a biosynthesis pathway. Once delivered into cancerous cells, the nanocarriers are selectively turned on and distinctively fluoresce upon excitation. We, therefore, demonstrated the efficacy of the selective turn-on fluorescence of the nanocarriers in in vitro co-culture models and in vivo tumor-bearing models.
关键词： Hyaluronic Acid,Cancer Diagnosis,Biocompatible Nanocarrier,Turn-on Fluorescence,5-Aminolevulinic Acid
更新于2025-09-23 15:22:29
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Regression Analysis of Protoporphyrin IX Measurements Obtained During Dermatological Photodynamic Therapy
摘要： Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of dermatological cancers and precancers. Improvement of efficacy is required to widen its application. Clinical protoporphyrin IX (PpIX) fluorescence data were obtained using a pre-validated, non-invasive imaging system during routine methyl aminolevulinate (MAL)-PDT treatment of 172 patients with licensed dermatological indications (37.2% actinic keratosis, 27.3% superficial basal cell carcinoma and 35.5% Bowen’s disease). Linear and logistic regressions were employed to model any relationships between variables that may have affected PpIX accumulation and/or PpIX photobleaching during irradiation and thus clinical outcome at three months. Patient age was found to be associated with lower PpIX accumulation/photobleaching, however only a reduction in PpIX photobleaching appeared to consistently adversely affect treatment efficacy. Clinical clearance was reduced in lesions located on the limbs, hands and feet with lower PpIX accumulation and subsequent photobleaching adversely affecting the outcome achieved. If air cooling pain relief was employed during light irradiation, PpIX photobleaching was lower and this resulted in an approximate three-fold reduction in the likelihood of achieving clinical clearance. PpIX photobleaching during the first treatment was concluded to be an excellent predictor of clinical outcome across all lesion types.
关键词： photobleaching,aminolevulinic acid (ALA; Ameluz),dermatology,protoporphyrin IX (PpIX),imaging,methyl aminolevulinate (MAL; Metvix),photodynamic therapy (PDT),fluorescence,non-melanoma skin cancer (NMSC)
更新于2025-09-23 15:22:29
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A Randomized, Vehicle-Controlled Phase 3 Study of Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses on the Upper Extremities
摘要： BACKGROUND Blue-light aminolevulinic acid photodynamic therapy (ALA-PDT) after broad-area application and 3-hour incubation is ef?cacious for actinic keratosis (AK) lesion clearance on upper extremities, with use of occlusive dressing signi?cantly increasing ef?cacy. OBJECTIVE To prove the safety and ef?cacy of ALA-PDT versus vehicle (VEH-PDT) in the spot treatment of multiple AKs on upper extremities. METHODS Aminolevulinic acid or VEH was spot applied only to lesions on one upper extremity 3 hours before blue-light exposure. Treated extremity was covered with occlusive dressing during incubation. Identical treatment was repeated at Week 8 if AK lesions were present in the treated area. RESULTS Thirty-one percent (42/135) of subjects treated with ALA-PDT had complete clearance at Week 12, compared with 13% (17/134) of the subjects treated with VEH-PDT (p = .0001). The mean AK lesion clearance rate for ALA-treated subjects at Weeks 8 and 12 was 53% and 69%, respectively, compared with 26% and 30% for the VEH-treated group (p < .0001, linear mixed model). Safety pro?le observed in this study is consistent with previous studies/reports in the literature, and the therapy was well tolerated overall. CONCLUSION Aminolevulinic acid-PDT spot treatment using a 3-hour occluded incubation was superior to VEH-PDT for AK lesion clearance of the upper extremity.
关键词： actinic keratosis,photodynamic therapy,aminolevulinic acid,upper extremities,blue light
更新于2025-09-16 10:30:52
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Evaluations of antibacterial effects of 5-aminolevulinic acids in combination with light emitting diode (LED: 635nm) with different disinfection methods
摘要： This study evaluates the in vitro antibacterial effects of 5-ALA (photoactive dye) in regard to different disinfection methods (2% Chlorhexidine gluconate, 1% Sodium Hypochlorite) on cariogenic bacteria (Streptococcus mutans and Streptococcus sobrinus). After inoculation of dentin specimens with S. mutans and S. sobrinus separately, the reduction in bacterial count was evaluated by the colony counting method. A total of sixty specimens were assigned to six groups (Ten per each group, with five in each group inoculated with S. mutans and the other five inoculated with S.sobrinus); group one: positive control where no treatment was performed, group two: 1% NaOCl was applied, group three: 2% CHX was used, group four: 5-ALA with LED light (635nm) was applied, group five: 5-ALA was used without LED light activation, group six: LED light was used without dye application. There was a significant reduction in the number of S. mutans in the group treated with 5-ALA with LED light, followed by CHX and then NaOCl, whilst minimum bacterial reduction was detected in the groups that were treated with LED light alone and 5-ALA without LED. However, NaOCl exhibited a better effect regarding reduction of S. sobrinus, followed by 5-ALA and LED light and then CHX. All the disinfected groups showed a significant relation with the positive control non-treated group(p<0.05).
关键词： Caries disinfection,5-Aminolevulinic acid,Streptococcus mutans,Photodynamic therapy,Streptococcus sobrinus
更新于2025-09-12 10:27:22
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Successful Treatment of Adult-Onset Recurrent Respiratory Papillomatosis with CO <sub/>2</sub> Laser and Photodynamic Therapy
摘要： Recurrent respiratory papillomatosis is a noninvasive benign epithelial tumor caused by human papillomavirus. Clinically, it featured rapid growth, multifocus, and frequent recurrence. Though a number of therapies have been investigated, the recurrence after treatment is always a challenge. In this report, we describe a 27-year-old male patient with recurrent respiratory papillomatosis who was treated with CO2 laser therapy followed by 5-aminolevulinic acid photodynamic therapy (ALA-PDT). There was no adverse reaction after treatment and no recurrence during the follow-up time.
关键词： CO2 laser therapy,5-aminolevulinic acid,human papillomavirus,photodynamic therapy,Recurrent respiratory papillomatosis
更新于2025-09-11 14:15:04