Carrier-Free Hybrid Nanoparticles for Enhanced Photodynamic Therapy in Oral Carcinoma via Reversal of Hypoxia and Oxidative Resistance.

In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor of N, N'-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+ present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ ion and the downregulation of the HIF-1α, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.

Efficacy of a Combination Treatment of Ablative Fractional Carbon Dioxide Laser Therapy and Recombinant Human Epidermal Growth Factor for Atrophic Acne Scars.

BACKGROUND: Atrophic acne scars (AAS) are disfiguring and permanent changes caused by inflammatory acne. Fractional carbon dioxide is a common ablative device used to treat this condition. However, issues such as unclear effectiveness, frequent treatments, and potential side effects exist. In recent years, recombinant human epidermal growth factor (rhEGF) has also been frequently reported for its application in the treatment of acne scars. OBJECTIVE: To explore the potential synergistic effect of fractional carbon dioxide laser combined with rhEGF in AAS treatment. METHODS: We enrolled 15 patients with AAS. They received fractional carbon dioxide laser treatment and were then randomly assigned to receive either rhEGF or a placebo on one side of the face. The procedure was repeated three times, and the results were evaluated using the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score and analyzed using the CBS camera system, 3D analysis (3DMD). Reflectance confocal microscopy (RCM) examination was also conducted. RESULTS: Both sides exhibited significant improvement in the appearance of the acne scars after treatment, as confirmed by the ECCA score, 3DMD data, and CBS texture score. On the rhEGF-treated side, the pore number and epidermal pigment area significantly improved as compared to the control side, whereas no significant differences were observed in the other data. Under RCM, a significant increase in epidermal thickness and appearance of reticular collagen fibers in the dermal layer after treatment was observed. CONCLUSION: Compared to the sole use of laser, the combination of fractional carbon dioxide laser and rhEGF does not significantly enhance scar therapeutic effects. However, it does shorten the recovery period after laser treatment and improves the pore appearance.

Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies.

Thrombosis is associated with various fatal arteriovenous syndromes including ischemic stroke, myocardial infarction, and pulmonary embolism. However, current clinical thrombolytic treatment strategies still have many problems in targeting and safety to meet the thrombolytic therapy needs. Understanding the molecular mechanism that underlies thrombosis is critical in developing effective thrombolytic strategies. It is well known that platelets play a central role in thrombosis and the binding of fibrinogen to activated platelets is a common pathway in the process of clot formation. Based on this, a concept of biomimetic thrombus-targeted thrombolytic strategy inspired from fibrinogen binding to activated platelets in thrombosis was proposed, which could selectively bind to activated platelets at a thrombus site, thus enabling targeted delivery and local release of thrombolytic agents for effective thrombolysis. In this review, we first summarized the main characteristics of platelets and fibrinogen, and then introduced the classical molecular mechanisms of thrombosis, including platelet adhesion, platelet activation and platelet aggregation through the interactions of activated platelets with fibrinogen. In addition, we highlighted the recent advances in biomimetic thrombus-targeted thrombolytic strategies which inspired from fibrinogen binding to activated platelets in thrombosis. The possible future directions and perspectives in this emerging area are briefly discussed.

Hyaluronic acid dissolving microneedle patch loaded with tranexamic acid for melasma treatment.

Melasma is an acquired hypermelanotic condition characterized by the presence of irregular light-to-dark brown macules that primarily manifest on the sun-exposed areas of the skin, particularly the face. The management of melasma poses significant challenges, as it is often recalcitrant to treatment and tends to recur despite successful treatment. In this study, we explored a safe, easy, and effective melasma treatment strategy. A hyaluronic acid (HA)-based microneedle (MN) patch loaded with tranexamic acid (TXA) was designed to deliver the necessary medication for melasma treatment. The MN patch features uniform needles with adequate mechanical strength and effective penetration and solubility in the skin without cytotoxicity. Remarkably, these MNs substantially reduce the thickness of the epidermis of melasma mice, curtail melanin production, and diminish dopachrome tautomerase (DCT) expression.

The Effectiveness of 595-nm Pulsed Dye Laser for the Treatment of Bilateral Cleft-Lip Scars in Asian Patients: A 6-Month Prospective, Randomized, Self-Controlled Trial.

Objective: This study is the first prospective within-patient self-controlled research seeking to investigate the safety and efficacy of 595 nm pulsed-dye laser (PDL) for the treatment of cleft-lip scars. Approach: This prospective, randomized, self-controlled study is based on the clinical records of the patients who received laser-assisted treatment due to bilateral cleft-lip scars. The bilateral scars were randomly assigned to the 595 nm PDL group with five consecutive sessions at 2-week intervals or control group in a blinded manner of evaluators, with subsequent follow-up for 6 months after the final treatment. Clinical efficacy and safety outcomes were evaluated by Vancouver Scar Scale (VSS), Patient Scar Assessment Questionnaire (PSAQ), and other objective evaluations. Results: A total of 18 patients were included. The 595 nm PDL-treated sides showed statistically significant improvement in VSS after treatment at follow-up compared with the baseline (p < 0.05). Interestingly, the 595 nm-PDL-treated side achieved significantly better improvement in scar pigmentation and pliability (p < 0.05). Though there was statistically significant difference between two groups (p < 0.05), the gap in overall PSAQ is not obvious. And comparison by area and coloring evaluation (E/M index) also suggests that the responses of scars to treatment by PDL were slightly improved (p < 0.05). Innovation and Conclusion: It is the first time to apply the 595nm PDL for cleft-lip scars. It would be a better choice for the early treatment of red scar with proliferative tendency after cleft-lip surgery.

Evaluation of a Novel Microfocused Ultrasound with Three-Dimensional Digital Imaging for Facial Tightening: A Prospective, Randomized, Controlled Trial.

BACKGROUND: The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures. OBJECTIVE: We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound. METHODS: The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded. RESULTS: A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P < 0.05). The mean volumetric change in the lower face, as quantitatively assessed after 3 months was -0.29 mL compared with +0.42 mL on the control side (P < 0.05). The VAS pain score was 3.00 ± 1.19 without any oral or intramuscular anesthesia. CONCLUSIONS: A small sample size, lack of clinical scales, and impersonalized treatment parameters. The novel microfocused ultrasound appears to be a safe and effective modality for lower-face tightening. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR 2200064666.

Optimal Timing of Fractional CO 2 Laser on Cleft Lip Scars: A Single-Blind Randomized Controlled Cohort Study.

OBJECTIVE: To determine the optimal time to apply a fractional CO 2 laser for the treatment of postsecondary repair scars in patients with cleft lip. METHODS: Forty-two patients with linear scarring after cleft lip repair were recruited from November 2021 to October 2022. A single-blind, randomized, controlled cohort study was conducted to examine the impact of fractional CO 2 laser treatment compared with conventional conservative treatment. Thirty patients started laser treatment at 1 month ( n = 10), 3 months ( n = 10), and 6 months ( n = 10) postoperatively, and 12 patients were in the control group. Each patient was treated with high-energy low-density fractional CO 2 laser treatment 3 times at an interval of 1 month. The Vancouver Scar Scale (VSS) was used for scar evaluation to determine vascularity, pigmentation, pliability, and height. RESULTS: The VSS scores decreased significantly after laser treatment ( p < .05), with the most significant improvement in scars in the group that started treatment 1 month after the surgery. CONCLUSION: Early postoperative fractional CO 2 laser treatment of cleft lip scars is more effective than later treatment.

Use of Reflectance Confocal Microscopy to Predict Treatment Efficacy in Café Au Lait Macules.

BACKGROUND: Multiple lasers have been used for the treatment of café au lait macules (CALMs) with various results. Objective tools to predict therapeutic efficacy of CALMs treatment is lacking. OBJECTIVE: To determine whether reflectance confocal microscopy (RCM) characteristics correlate with CALMs response to laser treatment. MATERIALS AND METHODS: All CAMLs underwent RCM examination of length and density of dermal papillae followed by 3 sessions of Q-switched alexandrite laser (QSAL). A visual analog scale was used to assess clinical treatment efficacy. RESULTS: Forty-three patients were included, 22 had CALMs with irregular borders and 21 with smooth borders. Café au lait macules with irregular border had shorter rete pegs and less papillae (p < .05) on RCM compared with smooth border CAMLs and responded better to QSAL treatment (2.32 vs 1.10). CONCLUSION: Reflectance confocal microscopy measurement of length and density of papillae were inversely correlated with treatment response. Reflectance confocal microscopy may be a useful tool to predict CALMs response to laser treatment.

Comparison of changes in wound healing parameters following treatment with three topical wound care products using a laser wound model.

PURPOSE: This study intended to analyze the differences in the efficacy of three topical wound care products on wound healing in patients undergoing surgery under the laser wound model. METHOD: A total of 130 patients in the department of dermatology enrolled for retrospective analysis. These patients were divided into group A (n=43, Zihua Shaoshang Ruangao), group B (n=43, Shengji Yuhong Gao), and group C (n=44, Shirun Shaoshang Gao), respectively, according to the type of wound care product administrated. The efficacy was compared during one month of treatment. RESULTS: There was little difference among groups A, B, and C in VAS score, FGF, EGF, and concentration of substance P (SP) at 1, 3, 5, 7, and 10 days after surgery (P>0.05), and a significant difference in these parameters among different time points was observed for intra-group comparison (P<0.05). There was no significant difference in the symptom scores at 1, 5, 10, 15, 20, 25, and 30 days after surgery among the three groups (P>0.05), while there was statistically significant difference at different time points in the same group (P<0.05). The wound healing rates at 10, 20, and 30 days after surgery were 25.58%, 65.12%, and 95.35% in group A, 20.93%, 67.44%, and 100.00% in group B and 25.00%, 59.09%, and 97.73% in group C respectively (P>0.05). The patients' satisfaction rate towards the appearance was 95.35% in group A, 97.67% in group B, and 97.73% in group C (P>0.05). CONCLUSION: The three kinds of wound care products, namely Zihua Shaoshang Ruangao, Shengji Yuhong Gao and Shirun Shaoshang Gao, exhibited good efficacy on the wound care of patients after dermatologic surgery. The wounds could be improved quickly, and patients were highly satisfied with the new appearance of the wound. Clinically, wound care products can be selected according to the stock of products in the hospital and patients' preferences.

Nanobody modified high-performance AIE photosensitizer nanoparticles for precise photodynamic oral cancer therapy of patient-derived tumor xenograft.

Photodynamic therapy (PDT) is a promising noninvasive treatment option for patients suffering from superficial tumors, such as oral cancer. However, for photosensitizers (PSs), it remains a grand challenge to simultaneously excel in all the key performance indicators including effective singlet oxygen (1O2) generation under clinical laser, specific targeting function and stable far-red (FR)/near-infrared (NIR) emission with low dark toxicity. In addition, traditional PS nanoparticles (NPs) for clinical use suffer from quenched fluorescence and reduced 1O2 production caused by molecular aggregation. To address these issues, AIEPS5 with aggregation-induced FR/NIR emission and effective 1O2 generation under 532 nm laser irradiation is designed by precise optimization of the chemical structure. By attaching a polyethylene glycol (PEG) chain onto AIEPS5, the yielded amphiphilic AIEPS5-PEG2000 can spontaneously self-assemble into water dispersible NPs, which are further endowed with targeted delivery function via the decoration of anti-Her-2 nanobody (NB). The bespoke AIEPS5-NPs-NB exhibit effective 1O2 generation capability, bright FR/NIR emission centered at 680 nm, and negligible dark toxicity, which outperform Heimbofen, a clinically approved PS in PDT using a patient-derived tumor xenograft model.

Fluorinated chitosan-mediated intracellular catalase delivery for enhanced photodynamic therapy of oral cancer.

A pH-responsive fluorinated chitosan-chlorin e6 (FC-Ce6) was employed here for the intracellular delivery of catalase to relieve the hypoxic micro-environment. Upon simple mixing, FC-Ce6 and catalase co-assemble to form stable nanoparticles, which show a greatly improved cross-membrane penetration capacity compared with catalase alone or nonfluorinated CS-Ce6/catalase nanoparticles. Under catalase catalysis, a high concentration of intracellular H2O2 can be transformed into O2. Upon irradiation, due to the continuous formation of cytotoxic singlet oxygen (1O2), our nanoparticles showed superior anti-cancer activity in contrast to free Ce6 and nonfluorinated CS-Ce6/catalase nanoparticles. Our study proposes an effective intracellular catalase delivery system to overcome hypoxia for enhanced PDT against oral cancer.

Reflectance confocal microscopy characteristics of oral lichen planus: An analysis of 47 cases in a Chinese cohort.

Reflectance confocal microscopy (RCM) is a non-invasive tool that provides real-time microscopic images and relatively high-resolution tissue images. This technique provides a link between clinical examination and histopathology. RCM has been used to detect skin diseases and has also recently been applied to diseases of the oral mucosa. The present study aimed to explore the features of oral lichen planus (OLP) using RCM. A total of 47 patients with OLP exhibiting a reticular pattern, were included in the present study. The lesion sites and healthy adjacent sites were examined using in vivo RCM, with the lesion being histopathologically confirmed after RCM examination. The confocal images were reviewed, and the features were described. Sensitivity and specificity analysis of the RCM features was also performed. RCM examination presented parakeratosis, acanthosis and connective tissue papillae disappearance, with the presence of large melanocytes and roundish inflammatory cell infiltration, as well as dilated vessels in the lesion tissue. The sensitivity and specificity of OLP for dorsal tongue lesions were not as satisfactory as those on other sites. The results implied that RCM may be a promising technique to detect OLP non-invasively in vivo.

Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment.

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

A NIR-triggered gatekeeper of supramolecular conjugated unimicelles with two-photon absorption for controlled drug release.

A near-infrared (NIR)-sensitive gated assembly of supramolecular conjugated unimicelles based on robust host-guest recognition between a ß-cyclodextrin-grafted hyperbranched conjugated polymer and azobenzene-functionalized poly(ethylene glycol) was constructed. Utilized as a drug carrier, these unimicelles exhibited controlled drug release through the NIR-triggered photoisomerization of azobenzene in cancer cells via a two-photon excited fluorescence resonance energy transfer (TP-FRET) approach, leading to efficient cancer therapy.

pH-Responsive Aerobic Nanoparticles for Effective Photodynamic Therapy.

RATIONALE: Photodynamic therapy (PDT), an O2-dependent treatment for inhibition of cancer proliferation, suffers from the low therapeutic effect in clinical application due to the hypoxic microenvironment in tumor cells. METHODS: To overcome this obstacle, a stimuli-responsive drug delivery system with O2 self-sufficiency for effective PDT was developed. In this study, pH-responsive aerobic nanoparticles were prepared by the electrostatic interaction between the O2-evolving protein Catalase and Chitosan. Subsequently, the photosensitizer Chlorin e6 (Ce6) was encapsulated in the nanoparticles. RESULTS: The nanoparticles exhibited high stability in aqueous medium and efficient cellular uptake by tumor cells facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. In acidic environment, irradiation caused disassembly of the nanoparticles resulting in the quick release of Catalase and the photosensitizer with continuous formation of cytotoxic singlet oxygen (1O2) greatly enhancing the PDT efficacy in hypoxic tumor tissues both in vitro and in vivo biological studies. CONCLUSION: Due to the unique O2 self-sufficiency, the nanoparticles, upon irradiation, exhibited higher anticancer activity than free Ce6 both in vitro and in vivo. Our work has identified a new pH-triggered strategy to overcome hypoxia for effective PDT against cancer cells.

Color-Convertible, Unimolecular, Micelle-Based, Activatable Fluorescent Probe for Tumor-Specific Detection and Imaging In Vitro and In Vivo.

Recent years have witnessed significant progress in molecular probes for cancer diagnosis. However, the conventional molecular probes are designed to be "always-on" by attachment of tumor-targeting ligands, which limits their abilities to diagnose tumors universally due to the variations of targeting efficiency and complex environment in different cancers. Here, it is proposed that a color-convertible, activatable probe is responding to a universal tumor microenvironment for tumor-specific diagnosis without targeting ligands. Based on the significant hallmark of up-regulated hydrogen peroxide (H2 O2 ) in various tumors, a novel unimolecular micelle constructed by boronate coupling of a hydrophobic hyperbranched poly(fluorene-co-2,1,3-benzothiadiazole) core and many hydrophilic poly(ethylene glycol) arms is built as an H2 O2 -activatable fluorescent nanoprobe to delineate tumors from normal tissues through an aggregation-enhanced fluorescence resonance energy transfer strategy. This color-convertible, activatable nanoprobe is obviously blue-fluorescent in various normal cells, but becomes highly green-emissive in various cancer cells. After intravenous injection to tumor-bearing mice, green fluorescent signals are only detected in tumor tissue. These observations are further confirmed by direct in vivo and ex vivo tumor imaging and immunofluorescence analysis. Such a facile and simple methodology without targeting ligands for tumor-specific detection and imaging is worthwhile to further development.

Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer.

Activation of the epithelial to mesenchymal transition (EMT) in photodynamic therapy (PDT) can lead to the recurrence and progression of tumors. To enhance the effects of PDT, it is essential to inhibit the Wnt/ß-catenin signaling pathway involved in EMT progression. Herein, we used polyethylene glycol-polyethyleneimine-chlorin e6 (PEG-PEI-Ce6) nanoparticles to efficiently deliver Wnt-1 small interfering RNA (siRNA) to the cytoplasm of KB cells (oral squamous cell carcinoma) that were subjected to PDT. Wnt-1 siRNA effectively inhibited the Wnt/ß-catenin signaling pathway, reducing the expression of Wnt-1, ß-catenin and vimentin that are crucial to the EMT. Combined with Wnt-1 siRNA, PEG-PEI-Ce6 nanoparticle mediated PDT inhibited cell growth and enhanced the cancer cell killing effect remarkably. Our results show the promise of combination therapy of PEG-PEI-Ce6 nanoparticles for delivery of Wnt-1 siRNA along with PDT in the treatment of oral cancer.

Correction: Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer.

Correction for 'Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer' by Chuan Ma, et al., Biomater. Sci., 2017, DOI: 10.1039/c6bm00833j.

Combining Two-Photon-Activated Fluorescence Resonance Energy Transfer and Near-Infrared Photothermal Effect of Unimolecular Micelles for Enhanced Photodynamic Therapy.

Recent years have witnessed significant progress in the field of two-photon-activated photodynamic therapy (2P-PDT). However, the traditional photosensitizer (PS)-based 2P-PDT remains a critical challenge in clinics due to its low two-photon absorption (2PA) cross sections. Here, we propose that the therapeutic activity of current PSs can be enhanced through a combination of two-photon excited fluorescence resonance energy transfer (FRET) strategy and photothermal effect of near-infrared (NIR) light. A core-shell unimolecular micelle with a large two-photon-absorbing conjugated polymer core and thermoresponsive shell was constructed as a high two-photon light-harvesting material. After PSs were grafted onto the surface of a unimolecular micelle, the FRET process from the conjugated core to PSs could be readily switched "on" to kill cancer by the collapsed thermoresponsive shell due to the photothermal effect of NIR light. Such NIR-triggered FRET leads to an enhanced 2PA activity of the traditional PSs and, in turn, amplifies their cytotoxic singlet oxygen generation. Eventually, both in vitro and in vivo PDT efficiencies treated with the thermoresponsive micelles were dramatically enhanced under NIR light irradiation, as compared to pure PSs excited by traditional visible light. Such a facile and simple methodology for the enhancement of the photodynamic antitumor effect holds great promises for cancer therapy with further development.

A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris.

OBJECTIVE: This study investigated the efficacy and safety of a newly designed LED device used in photodiagnosis and photodynamic therapy of moderate to severe acne vulgaris in Chinese patients. METHODS: Forty-six patients with moderate to severe facial acne showing high degrees of fluorescence by ultraviolet light examination were illuminated during ALA-PDT with two wavelengths of light (543-548 nm, and 630±6 nm, respectively) after 2 h of incubation with ALA. Each patient received treatment once every 30 days for two or three sessions. Two independent investigators assigned an acne severity score at baseline, one week after each treatment, as well as 4, 8, and 12 weeks after the completion of treatment. Adverse effects were recorded during and after each treatment. All patients rated their satisfaction with the results of treatment at a 12-week follow up visit. RESULTS: The ALA-PDL treatment regimen showed an overall effectiveness rate of 89.13% (41/46 patients). Some degree of clinical efficacy was seen in 71.42%, 86.67%, and 95.83% of patients with grades IV, V, and VI acne, respectively, and the rate of clinical effectiveness increased with increasing acne severity. When compared with baseline scores, significant reductions in acne scores were obtained at 8, and 12 weeks after completion of treatment. Maximum efficacy was shown at the 12 week follow up. No severe adverse events were observed. CONCLUSION: ALA-PDT administered with the newly designed LED device was an effective treatment for moderate to severe acne vulgaris, and side effects were mild and reversible.