RESUMO
BACKGROUND: Warts are one of the most common benign neoplasms caused by human papillomavirus infection and often pose a therapeutic challenge. OBJECTIVE: To summarize the current evidence on the safety and efficacy of laser and energy-based devices for the treatment of cutaneous verrucae. METHODS: A comprehensive systematic review of the literature on laser and energy-based devices for the treatment of cutaneous verrucae was performed. RESULTS: A total of 904 unique studies were identified, of which 109 were included in this review. The most commonly used lasers as a single treatment modality for verrucae included the long-pulsed Nd:Yag (n = 20) and pulsed dye (n = 18) lasers. Other modalities included the CO2 ablative laser (n = 10), photodynamic therapy (n = 11), local hyperthermia (n = 11), microwave therapy (n = 2), and nanopulse stimulation (n = 1). Other studies combined energy-based modalities with additional treatments, such as retinoids, imiquimod, and intralesional bleomycin. Overall, such devices were generally well-tolerated, with only a mild side effect profile. CONCLUSION: Overall, the use of laser and energy-based devices is a safe and well-tolerated option for cutaneous verrucae that is relatively less invasive than surgical interventions. Future studies using more consistent outcome assessment tools will be valuable to help clinicians develop device-specific protocols and treatment regimens to ensure replicable and effective outcomes.
Assuntos
Verrugas , Humanos , Verrugas/terapia , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Fotoquimioterapia/métodos , Fotoquimioterapia/instrumentação , Resultado do Tratamento , Hipertermia Induzida/instrumentação , Hipertermia Induzida/métodos , Lasers de Gás/uso terapêuticoRESUMO
Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fotoquimioterapia/instrumentação , Humanos , Células HT29 , Ácido Aminolevulínico/administração & dosagemRESUMO
An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm3) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.
Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Tecnologia sem Fio/instrumentação , Animais , Clorofilídeos , Relação Dose-Resposta a Droga , Fontes de Energia Elétrica , Desenho de Equipamento , Implantes Experimentais , Camundongos Endogâmicos C57BL , Miniaturização , Neovascularização Patológica , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Porfirinas/farmacocinética , Neoplasias da Bexiga Urinária/irrigação sanguínea , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report a detailed investigation of the interaction of Cr(NN)33+ with bovine serum albumin (BSA), an important protein for the transport of drugs in blood plasma which allows us to understand further the role of Cr(NN)33+ as a sensitizer in photodynamic therapy (PDT). Chromium(III) complexes, Cr(5Cl-phen)33+, Cr(5Me-phen)33+ and Cr(5Ph-phen)33+ (where Cl = chlorine, Me = methyl and Ph = phenyl are substituents in position 5 of the phen = 1,10-phenanthroline bidentate ligand), were used for the present study. The interactions of BSA with Cr(NN)33+ were assessed employing fluorescence spectroscopy and UV-Vis absorption spectroscopy; in addition electrochemical experiments carried out at a liquid/liquid interface gave insight into the relative hydrophobicities of the complexes. We found that chromium complexes bind strongly with bovine serum albumins (BSA) with intrinsic binding constants, Kb, of (3.33 ± 0.08) × 105 M-1, (5.92 ± 0.08) × 105 M-1 and (1.64 ± 0.05) × 105 M-1 at 300.3 K. Analysis of the thermodynamic parameters ΔG, ΔH, and ΔS indicated that hydrophobic interactions played a major role in all the BSA-Cr(NN)33+ association processes. The binding distances and transfer efficiencies for BSA binding reactions were calculated according to the Förster theory of non-radiation energy transfer giving distance (r) of 2.63 nm, 2.94 nm and 3.00 nm for 5Clphen, 5Mephen and 5Ph phenanthroline complexes, respectively. All these experimental results indicate that Cr(NN)33+ binds to serum albumins, by which these proteins could act as carriers of this complex for further applications in PDT.
Assuntos
Compostos de Cromo/química , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/farmacologia , Soroalbumina Bovina/química , Animais , Bovinos , Eletroquímica , Transferência Ressonante de Energia de Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Cinética , Ligantes , Estrutura Molecular , Fenantrolinas/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica , Triptofano/químicaRESUMO
BACKGROUND: No large studies have defined the best treatment of actinic cheilitis. METHODS: We conducted a systematic review to define the best therapies for actinic cheilitis in clinical response and recurrences. RESULTS: We first identified 444 papers, and 49 were finally considered, including 789 patients and 843 treated areas. The following therapies were recorded in order of frequency: laser therapy, photodynamic therapy (PDT), 3% diclofenac in 2.5% hyaluronic acid, PDT + 5% imiquimod, aminolevulinic acid-laser or methyl-aminolevulinic acid-laser, 5% imiquimod, fluorouracil, partial surgery, 0.015% ingenol mebutate, 50% trichloroacetic acid, and laser + PDT. Concerning the primary outcome, complete clinical response was achieved in 76.5% of patients, and 10.2% had clinical recurrences. Partial surgery and laser therapy showed the highest complete response rates (14 of 14 [100%] and 244 of 260 [93.8%], respectively) with low recurrences. Only a limited number of patients were treated with other therapies, with the exception of PDT, with 68.9% complete responses and 12.6% of recurrences. Interestingly, when combined with 5% imiquimod, the efficacy of PDT was significantly enhanced. LIMITATIONS: Heterogeneity across studies. CONCLUSION: Laser therapy appears the best option among nonsurgical approaches for actinic cheilitis, and PDT showed higher efficacy when sequentially combined with 5% imiquimod. Larger studies are needed to confirm these data.
Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Queilite/terapia , Neoplasias Labiais/prevenção & controle , Lesões Pré-Cancerosas/terapia , Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/patologia , Queilite/patologia , Terapia Combinada/métodos , Dermabrasão/métodos , Diclofenaco/uso terapêutico , Progressão da Doença , Fluoruracila/uso terapêutico , Humanos , Imiquimode/uso terapêutico , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Neoplasias Labiais/patologia , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Lesões Pré-Cancerosas/patologia , Resultado do TratamentoRESUMO
PURPOSE: To assess corneal concentration of riboflavin in two different corneal crosslinking protocols performed by a novel image-guided therapeutic (or "theranostic") UV-A device. METHODS: Ten human eye bank donor tissues were used in this work. The tissues underwent corneal cross-linking according to the conventional treatment protocol (n = 5; 30 min of stromal soaking followed by 30 min of 3 mW/cm2 UV-A irradiance) and the iontophoresis-assisted transepithelial protocol (n = 5; soaking for 5 min at 1 mA/min and 9 min of 10 mW/cm2 UV-A irradiance) using a theranostic UV-A device (Vision Engineering Italy srl, Italy). The device provided real time assessment of riboflavin concentration by hyperspectral image analysis of the cornea. A 0.1% riboflavin hypotonic solution (Ricrolin+, Sooft Italia Spa, Italy) was used in all cases. RESULTS: Manual application of hypotonic riboflavin for 30 min into the stroma achieved greater corneal riboflavin concentration (425 ± 77 µg/cm3) than transepithelial delivery of riboflavin by corneal iontophoresis (195 ± 35 µg/cm3; P = 0.001). In both UV-A irradiation protocols, corneal riboflavin concentration decreased exponentially with a constant energy rate of 2.3 ± 0.5 J/cm2 and 1.8 ± 0.3 J/cm2 respectively. At the end of treatment, the average corneal concentration of riboflavin decreased by ≥ 85%, with values of 54 ± 29 µg/cm3 and 31 ± 9 µg/cm3 (P = 0.11), respectively. CONCLUSION: Manual application of riboflavin onto the stroma achieved almost 50% greater concentration of riboflavin than transepithelial delivery by corneal iontophoresis. The theranostic UV-A device provided a novel approach to estimate corneal concentration of riboflavin non-invasively during treatment.
Assuntos
Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/tratamento farmacológico , Fotoquimioterapia/instrumentação , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade Visual , Idoso , Desenho de Equipamento , Feminino , Humanos , Ceratocone/diagnóstico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Doadores de TecidosRESUMO
BACKGROUND AND OBJECTIVES: Intraoperative photodynamic therapy (IO-PDT) is typically administered by a handheld light source. This can result in uncontrolled distribution of light irradiance that impacts tissue and tumor response to photodynamic therapy. The objective of this work was to characterize a novel optical surface applicator (OSA) designed to administer controlled light irradiance in IO-PDT. STUDY DESIGN/MATERIALS AND METHODS: An OSA was constructed from a flexible silicone mesh applicator with multiple cylindrically diffusing optical fibers (CDF) placed into channels of the silicone. Light irradiance distribution, at 665 nm, was evaluated on the OSA surface and after passage through solid tissue-mimicking optical phantoms by measurements from a multi-channel dosimetry system. As a proof of concept, the light administration of the OSA was tested in a pilot study by conducting a feasibility and performance test with 665-nm laser light to activate 2-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) in the thoracic cavity of adult swine. RESULTS: At the OSA surface, the irradiance distribution was non-uniform, ranging from 128 to 346 mW/cm2 . However, in the tissue-mimicking phantoms, beam uniformity improved markedly, with irradiance ranges of 39-153, 33-87, and 12-28 mW/cm2 measured at phantom thicknesses of 3, 5, and 10 mm, respectively. The OSA safely delivered the prescribed light dose to the thoracic cavities of four swine. CONCLUSIONS: The OSA can provide predictable light irradiances for administering a well-defined and potentially effective therapeutic light in IO-PDT. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Assuntos
Lasers Semicondutores/uso terapêutico , Fotoquimioterapia/instrumentação , Cavidade Torácica/efeitos da radiação , Animais , Humanos , Imagens de Fantasmas , Silicones , SuínosRESUMO
BACKGROUND: Light-emitting diodes (LEDs) may be used as an activating light source for photosensitizers in photodynamic therapy (PDT), a form of noninvasive phototherapy. Photodynamic therapy for aesthetic dermatologic conditions has demonstrated skin rejuvenating effects. OBJECTIVE: To evaluate the safety and efficacy of PDT using LEDs to treat aesthetic dermatologic conditions including photoaged skin, scarring, and dyspigmentation. MATERIALS AND METHODS: A search of PubMed and EMBASE databases was conducted through May 31, 2019, to identify studies that used LEDs as a light source for PDT and evaluated cosmetic improvements as the primary outcome measure. RESULTS: A total of 24 original articles were included in the authors' systematic review. The available evidence supports methyl aminolevulinate or 5-aminolevulinic acid incubation followed by LED treatment for global improvement of skin quality, including smoother texture, reduction of rhytides, and improvement of scars. Histologic analysis for global skin improvement demonstrated increased collagen fibers and decreased elastin fibers after LED-mediated PDT. CONCLUSION: Light-emitting diode-based PDT seems to have beneficial effects for photoaging, scars and dyspigmentation. A paucity of high-quality studies using LED-based PDT for aesthetic outcomes was found, highlighting the need for well-designed randomized control trials on this topic.
Assuntos
Cicatriz/tratamento farmacológico , Fotoquimioterapia/instrumentação , Transtornos da Pigmentação/tratamento farmacológico , Semicondutores , Envelhecimento da Pele/efeitos da radiação , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/análogos & derivados , Humanos , Luz , Fármacos Fotossensibilizantes/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Rejuvenescimento , Resultado do TratamentoRESUMO
Photodynamic therapy (PDT) has long been known as an effective method for treating surface cancer tissues. Although this technique is widely used in modern medicine, some novel approaches for deep lying tumors have to be developed. Recently, deeper penetration of X-rays into tissues has been implemented, which is now known as X-ray photodynamic therapy (XPDT). The two methods differ in the photon energy used, thus requiring the use of different types of scintillating nanoparticles. These nanoparticles are known to convert the incident energy into the activation energy of a photosensitizer, which leads to the generation of reactive oxygen species. Since not all photosensitizers are found to be suitable for the currently used scintillating nanoparticles, it is necessary to find the most effective biocompatible combination of these two agents. The most successful combinations of nanoparticles for XPDT are presented. Nanomaterials such as metal-organic frameworks having properties of photosensitizers and scintillation nanoparticles are reported to have been used as XPDT agents. The role of metal-organic frameworks for applying XPDT as well as the mechanism underlying the generation of reactive oxygen species are discussed.
Assuntos
Nanocompostos/química , Nanopartículas/química , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Radical Hidroxila/química , Estruturas Metalorgânicas , Camundongos , Nanotecnologia/métodos , Transplante de Neoplasias , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/química , Raios XRESUMO
BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.
Assuntos
Dermatoses Faciais/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Dor Processual/diagnóstico , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/administração & dosagem , Dermatoses do Couro Cabeludo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/efeitos adversos , Ácido Aminolevulínico/análogos & derivados , Dermatoses Faciais/patologia , Feminino , Testa , Humanos , Ceratose Actínica/patologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Processual/etiologia , Medidas de Resultados Relatados pelo Paciente , Fotoquimioterapia/efeitos adversos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Couro Cabeludo , Dermatoses do Couro Cabeludo/patologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: To investigate the efficacy and safety of the retention ring-assisted continuous application of 0.1% riboflavin in pulsed-light accelerated corneal collagen cross-linking on the progression of keratoconus. METHODS: The medical records of 20 eyes of 18 patients with progressive keratoconus who received collagen cross-linking at Seoul National University Hospital were retrospectively reviewed. Isotonic 0.1% riboflavin was continuously applied for 10 min using an 8.0-mm retention ring before the irradiation and accelerated cross-linking was applied with 30-mW pulsed-ultraviolet light at a wavelength 365 nm for eight minutes (1 s on/1 s off; 30 mW/cm2, cumulative dose of 7 .2J/cm2) without further intermittent application of riboflavin. Visual acuity, refractive error, topographic index, corneal thickness, and endothelial cell density were evaluated before the operation and at 1, 3, 6, and 12 months. RESULTS: The best corrected visual acuity in logMAR improved from preoperative 0.43 to 0.17 in 12 months (p = 0.050). Maximum keratometry decreased from 51.8 D to 50.4 D at 6 months (p = 0.015) and 50.1 D at 12 months (p = 0.0003). Astigmatism decreased from preoperative 5.5 D to 4.1 D at 12 months (p < 0.0001). Thinnest corneal thickness decreased at three and 6 months but recovered in 12 months (p > 0.05). Endothelial cell density decreased at postoperative 1 month (p = 0.02) but gradually recovered in 12 months (p > 0.05). CONCLUSIONS: Retention ring-assisted continuous application of riboflavin for 10 minutes in pulsed-light accelerated cross-linking is a comparably safe and effective treatment for halting the progression of keratoconus in 12 months when compared to outcomes of the standard Dresden protocol shown in previous reports.
Assuntos
Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Riboflavina/administração & dosagem , Adolescente , Adulto , Colágeno/metabolismo , Perda de Células Endoteliais da Córnea/patologia , Progressão da Doença , Feminino , Humanos , Soluções Isotônicas/administração & dosagem , Ceratocone/fisiopatologia , Masculino , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/uso terapêutico , Erros de Refração/fisiopatologia , Estudos Retrospectivos , Raios Ultravioleta , Acuidade Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: Photodynamic therapy (PDT) using δ-aminolevulinic acid (ALA) photosensitization has shown promise in clinical studies for the treatment of early-stage oral malignancies with fewer potential side effects than traditional therapies. Light delivery to oral lesions can also carried out with limited medical infrastructure suggesting the potential for implementation of PDT in global health settings. OBJECTIVES: We sought to develop a cost-effective, battery-powered, fiber-coupled PDT system suitable for intraoral light delivery enabled by smartphone interface and embedded electronics for ease of operation. METHODS: Device performance was assessed in measurements of optical power output, spectral stability, and preclinical assessment of PDT response in ALA-photosensitized squamous carcinoma cell cultures and murine subcutaneous tumor xenografts. RESULTS: The system achieves target optoelectronic performance with a stable battery-powered output of approximately 180 mW from the fiber tip within the desired spectral window for PpIX activation. The device has a compact configuration, user friendly operation and flexible light delivery for the oral cavity. In cell culture, we show that the overall dose-response is consistent with established light sources and complete cell death of ALA photosensitized cells can be achieved in the irradiated zone. In vivo PDT response (reduction in tumor volume) is comparable with a commercial 635 nm laser. CONCLUSIONS: We developed a low-cost, LED-based, fiber-coupled PDT light delivery source that has stable output on battery power and suitable form factor for deployment in rural and/or resource-limited settings. Lasers Surg. Med. 9999:1-7, 2018. © 2018 Wiley Periodicals, Inc.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Luz , Neoplasias Bucais/tratamento farmacológico , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Países em Desenvolvimento , Feminino , Humanos , Camundongos , Camundongos Nus , Fibras Ópticas , Fotoquimioterapia/métodos , Smartphone , Resultado do TratamentoRESUMO
Development of versatile nanoscale platforms for cancer diagnosis and therapy is of great importance for applications in translational medicine. In this work, we present the use of γ-polyglutamic acid (γ-PGA) nanogels (NGs) to load polypyrrole (PPy) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)-sensitized tumor photothermal therapy (PTT). First, a double emulsion approach was used to prepare the cystamine dihydrochloride (Cys)-cross-linked γ-PGA NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole monomers that were subjected to in situ oxidation polymerization in the existence of Fe(III) ions. The formed uniform PPy-loaded NGs having an average diameter of 38.9 ± 8.6 nm exhibited good water-dispersibility and colloid stability. The prominent near-infrared (NIR) absorbance feature due to the loaded PPy endowed the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed excellent photothermal conversion efficiency (64.7%) and stability against laser irradiation, and could be adopted for PA imaging and PTT of cancerous cells and tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can be more significantly sensitized by RT using the sequence of laser irradiation followed by X-ray radiation as compared to using the reverse sequence. Our study suggests a promising theranostic platform of hybrid NGs that may be potentially utilized for PA imaging and combination therapy of different types of tumors.
Assuntos
Nanoestruturas/química , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Polímeros/química , Pirróis/química , Radioterapia/métodos , Animais , Feminino , Géis/administração & dosagem , Géis/química , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Neoplasias Experimentais/diagnóstico por imagem , Fotoquimioterapia/instrumentação , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/química , Polimerização , Raios X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Immune system evasion by cancer cells is one of the hallmarks of cancers, and it occurs with the support of tumor-associated immune cells (TICs) in the tumor microenvironment that increase the growth and invasiveness of tumor cells. With recent advancements in the development of novel near-infrared (NIR)-responsive nanoparticles, specifically eradicating TICs or inducing an inflammatory immune response by activating killer T cells has become possible. This review will discuss the mechanisms and applications of phototriggered immunotherapy in detail. In addition, various nanoparticles employed in phototriggered immunotherapy for cancer treatment will be covered. Furthermore, the challenges and future directions of phototriggered nanoparticle development for anticancer immunotherapy will be briefly discussed.
Assuntos
Imunoterapia/métodos , Nanopartículas/uso terapêutico , Neoplasias/terapia , Fototerapia/métodos , Microambiente Tumoral/imunologia , Animais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacologia , Humanos , Imunoterapia/instrumentação , Luz , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/patologia , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Fototerapia/instrumentação , Microambiente Tumoral/efeitos dos fármacosRESUMO
Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.
Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Humanos , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
BACKGROUND: Very few studies have assessed the efficacy of excimer in the treatment of palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol-clobetasol propionate combination. PURPOSE: To compare the effectiveness and safety of excimer lamp vs topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP. METHODS: This right-left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol-clobetasol combination (once daily) on another side for 12 weeks, followed by 8 weeks of follow-up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (mPPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP). Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤25%), mild (>25%-50%), moderate (>50%-75%), and marked (>75%). Secondary outcome measures were the proportion of patients achieving >75% reduction in mPPPASI and the time taken to achieve it. RESULTS: Of 36 recruited patients, 33 completed treatment and 21 adhered to 8-weeks follow-up. The mean mPPPASI on the excimer-treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (P < .001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow-up). The mean mPPPASI on the calcipotriol-clobetasol combination treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (P < .001) and 2.70 ± 3.97 at 12th week and 20th week, respectively. The reduction was significant for both treatment and the difference between the two was not statistically significant. Minimal, mild, moderate, and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol-clobetasol combination, respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4, and 8 weeks in 1, 2, and 8 patients, respectively, using either modalities. The adverse effects (most commonly hyperpigmentation) were noted more frequently on the excimer-treated sides; however, they were well tolerated. CONCLUSION: Both excimer lamp and calcipotriol-clobetasol propionate combination are equally effective in the treatment of PPP.
Assuntos
Calcitriol/análogos & derivados , Clobetasol/administração & dosagem , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Psoríase/tratamento farmacológico , Adulto , Idoso , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Clobetasol/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Bowen's disease (BD) is treated effectively with 5-aminolevulinic acid (ALA)-photodynamic therapy (ALA-PDT). Plum-blossom needling (PBN) may enhance topical drug delivery. OBJECTIVE: To compare the effects of and adverse reactions to PBN and ALA-PDT of BD with those associated with ALA-PDT alone. MATERIALS AND METHODS: Forty-three lesions from 24 patients were randomly assigned to 2 groups. The PBN-ALA-PDT group underwent vertical skin tapping with PBN before applying 10% ALA cream and narrow-band light-emitting diode irradiation (λ = 633 ± 10 nm; 100-200 J/cm). The ALA-PDT group received ALA cream and irradiation only. RESULTS: At 6 weeks, the PBN-ALA-PDT and ALA-PDT groups achieved complete response (CR) rates of 77.78% (14/18 lesions) and 40% (7/20 lesions), respectively, (p < .05), and 2/18 and 10/20 lesions, respectively, achieved CRs after further treatment; 2.9 ± 0.8 sessions and 3.4 ± 0.7 sessions, respectively, were required for the lesions to achieve CRs. The PBN-ALA-PDT group required fewer treatment sessions and had higher protoporphyrin IX fluorescence levels (p < .05). CONCLUSION: Plum-blossom needling may improve the efficacy of ALA-PDT by enhancing ALA delivery for BD treatment.
Assuntos
Ácido Aminolevulínico/administração & dosagem , Doença de Bowen/tratamento farmacológico , Agulhas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Sistemas de Liberação de Medicamentos/efeitos adversos , Sistemas de Liberação de Medicamentos/instrumentação , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/efeitos adversos , Fotoquimioterapia/instrumentação , Estudos Prospectivos , ProtoporfirinasRESUMO
Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm², fluence rate: 75 mW/cm²) and (ii) low light fluence and fluence rate (128 J/cm² and 14 mW/cm² and 128 J/cm² and 7 mW/cm²) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time.
Assuntos
Clorofila/análogos & derivados , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Glicoconjugados/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Radiometria/métodos , Animais , Carbocianinas/química , Carbocianinas/farmacocinética , Clorofila/síntese química , Clorofila/farmacologia , Neoplasias do Colo/patologia , Relação Dose-Resposta à Radiação , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Glicoconjugados/síntese química , Indóis/química , Indóis/farmacocinética , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica/métodos , Fotodegradação , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/síntese química , Propionatos/química , Propionatos/farmacocinética , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Espectrometria de Fluorescência/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Light-based acne treatments may represent a new emerging treatment for acne that does not increase the risk of bacterial resistance and they may be potentially effective with a favorable safety profile. Current data show that photodynamic therapy reduces inflammatory lesions and significantly improves acne. However, there is no consensus on the optimal implementation in the treatment of acne. In addition to topically applied photodynamic therapy, intense pulsed light, pulsed dye lasers, potassium-titanyl-phosphate lasers, infrared diode lasers, broad-spectrum continuous-wave light sources (red light, blue-red light) have been introduced as alternative treatments. Since well-designed studies to evaluate their efficacy versus traditional medical therapies are lacking and standardized regimens have not been agreed upon, procedures including laser, intense pulsed light, and photodynamic therapy should currently not be considered first-line treatment for inflammatory acne.
Assuntos
Acne Vulgar/terapia , Terapia a Laser/métodos , Fototerapia/métodos , Desenho de Equipamento , Humanos , Terapia a Laser/instrumentação , Lasers de Corante/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Fototerapia/instrumentação , Resultado do TratamentoRESUMO
BACKGROUND: Liposuction is one of the most performed cosmetic surgery procedures. In a previously reported study, gold-nanoparticle (GNP) laser-assisted liposuction (NanoLipo) was shown to improve procedure parameters and outcomes in a porcine model. OBJECTIVES: An ex vivo human liposuction model was developed to assess the ease, efficacy, and outcomes of NanoLipo, and to further explore its mechanism of action in facilitating liposuction. METHODS: NanoLipo was compared to a control without GNPs in sets of fresh, nonperfused, anatomically symmetric, matched tissue specimens from 12 patients. A subset of three experiments was performed under single-blinded conditions. Intraoperative assessments included lipoaspirate volume, percentage of free oil, ease of removal, and temperature rise. Specimens were palpated, visualized for evenness, and graded with and without skin. Postoperative assessment included viability staining of the lipoaspirate and remaining tissues. Microcomputed tomography was used to assess the distribution of infused GNPs within the tissues. RESULTS: NanoLipo consistently removed more adipose tissue with more liberated triglycerides compared to control. NanoLipo specimens were smoother, thinner, and had fewer and smaller irregularities. Infused solutions preferentially distributed between fibrous membranes and fat pearls. After NanoLipo, selective structural-tissue disruptions, indicated by loss of metabolic activity, were observed. Thus, NanoLipo likely creates a bimodal mechanism of action whereby fat lobules are dislodged from surrounding fibro-connective tissue, while lipolysis is simultaneously induced. CONCLUSIONS: NanoLipo showed many advantages compared to control under blinded and nonblinded conditions. This technology may be promising in facilitating fat removal.