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1.
Cochrane Database Syst Rev ; 3: CD013512, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33765359

RESUMO

BACKGROUND: Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze. OBJECTIVES: To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus. SEARCH METHODS: To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I2 = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I2 = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I2 = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported. AUTHORS' CONCLUSIONS: Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.


Assuntos
Colágeno/efeitos da radiação , Reagentes para Ligações Cruzadas/administração & dosagem , Ceratocone/radioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Riboflavina/administração & dosagem , Terapia Ultravioleta/métodos , Adulto , Viés , Paquimetria Corneana , Reagentes para Ligações Cruzadas/efeitos da radiação , Dextranos/administração & dosagem , Progressão da Doença , Epitélio Anterior/efeitos da radiação , Epitélio Anterior/cirurgia , Feminino , Humanos , Iontoforese/métodos , Masculino , Fármacos Fotossensibilizantes/efeitos da radiação , Ensaios Clínicos Controlados Aleatórios como Assunto , Riboflavina/efeitos da radiação , Terapia Ultravioleta/efeitos adversos , Acuidade Visual , Adulto Jovem
2.
Cancer Sci ; 112(3): 1326-1330, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33543819

RESUMO

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer treatment, which was recently approved in Japan for patients with inoperable head and neck cancer. NIR-PIT utilizes antibody-IRDye700DX (IR700) conjugates and NIR light at a wavelength of 690 nm. NIR light exposure leads to physicochemical changes in the antibody-IR700 conjugate cell receptor complex, inducing rapid necrotic cell death. Just as fluorescence guided surgery is useful for surgeons to resect tumors completely, real-time information of tumor locations would help clinicians irradiate NIR light more precisely. IR700 is a fluorescence dye that emits at 702 nm; however, there is no clinically available device optimized for detecting this fluorescence. On the other hand, many indocyanine green (ICG) fluorescence imaging devices have been approved for clinical use. Therefore, we investigated whether LIGHTVISION, one of the clinically available ICG cameras, could be employed for tumor detection. We hypothesized that irradiation with even low-power 690-nm laser light, attenuated by 99% with a neutral-density filter, could be detected with LIGHTVISION without fluorescence decay or therapeutic effect because of the long emission tail of IR700 beyond 800 nm (within the detection range of LIGHTVISION). We demonstrated that the LIGHTVISION camera, originally designed for ICG detection, can detect the tail of IR700 fluorescence in real time, thus enabling the visualization of target tumors.


Assuntos
Imunoterapia/métodos , Neoplasias/diagnóstico por imagem , Imagem Óptica/instrumentação , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Feminino , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Indóis/administração & dosagem , Indóis/química , Camundongos , Neoplasias/terapia , Compostos de Organossilício/administração & dosagem , Compostos de Organossilício/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Trastuzumab/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Medicine (Baltimore) ; 100(7): e24790, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607835

RESUMO

RATIONALE: Half-dose or reduced-fluence photodynamic therapy (PDT) with verteporfin has been well acknowledged to be the most effective and permanent treatment with very low rates of complications. However, we report a case of chronic central serous chorioretinopathy (CSC) who developed choroidal neovascularization (CNV) secondary to half-dose PDT within only 3 weeks. Such an occurrence following this short a course of treatment has not been reported previously. PATIENT CONCERNS: A 46-year-old Chinese man who had been diagnosed as acute more than 1 year ago revisited our department recently and complained of blurred vision again in his left eye. DIAGNOSES: Fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) revealed patchy hyperfluorescent dots and optical coherence tomography (OCT) indicated irregular flat pigment epithelium detachment (PED) in the central macula. The patient was diagnosed with chronic CSC. INTERVENTIONS: The patient was treated by half-dose PDT with verteporfin. Three weeks later, the patient complained of sudden blurred vision and fundus examination showed macular hemorrhages with a best-corrected visual acuity (BCVA) of 20/250. OCT angiography (OCTA) showed a distinct area of flower-like CNV located within the deep retinal slab. Secondary CNV had developed after a quite short course of half-dose PDT treatment. Subsequently, the patient was administered by 2 intravitreal injections of aflibercept (2 mg). OUTCOMES: Two months after the second intravitreal injection, macular hemorrhages and secondary CNV were completely resolved, and the BCVA improved to 20/25. LESSONS: Patients of chronic CSC with irregular PED who undergo PDT should be warned of secondary CNV within a short course after treatment. If happened, it should be treated by intravitreal injections of anti-vascular endothelial growth factor agents as soon as possible.


Assuntos
Coriorretinopatia Serosa Central/tratamento farmacológico , Neovascularização de Coroide/induzido quimicamente , Fármacos Fotossensibilizantes/efeitos adversos , Verteporfina/efeitos adversos , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Tomografia de Coerência Óptica , Verteporfina/administração & dosagem
4.
ACS Appl Mater Interfaces ; 13(4): 4861-4873, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471499

RESUMO

A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn@Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Manganês/administração & dosagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Ficocianina/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Bombyx/química , Cátions Bivalentes/administração & dosagem , Cátions Bivalentes/farmacologia , Cátions Bivalentes/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Fibroínas/química , Glutationa/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração de Íons de Hidrogênio , Manganês/farmacologia , Manganês/uso terapêutico , Camundongos , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos
5.
Int J Biol Macromol ; 168: 526-536, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33310104

RESUMO

Phototherapy holds promise in cancer treatment for its prominent antitumor efficacy and low systematic toxicity compared with traditional chemotherapy. However, the higher risk of tumor metastasis caused by the severe hypoxic state during phototherapy is a threat in practical use. Here, in order to tackle this challenge, we developed a delivery system via loading the photosensitizer indocyanine green (ICG) into the low molecular weight heparin (LMWH) modified liposomes (LMWH-ICG-Lip) to realize the synergistic effects between photosensitizer and drug vehicle, achieving better phototherapeutic efficacy and meanwhile alleviating the potential risk of tumor metastasis caused by phototherapy. In this system, besides elongating the photosensitizers' circulation time and enhancing their accumulating efficacy to tumor tissues, LMWH itself also exhibited anti-metastasis efficacy via inhibiting adhesion of platelets to tumor cells and decreasing migration and invasion capability of tumor cells. In vivo efficacy evaluation was conducted on orthotopic 4T1 breast cancer model, and the system of LMWH-ICG-Lip could alleviate metastasis potential of residual tumor cells after irradiation, and elicit optimistic antitumor and anti-metastasis efficacy for phototherapy.


Assuntos
Neoplasias da Mama/terapia , Heparina de Baixo Peso Molecular/química , Verde de Indocianina/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Lipossomos , Camundongos , Metástase Neoplásica , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Molecules ; 26(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374732

RESUMO

Endosomal escape in cell-penetrating peptide (CPP)-based drug/macromolecule delivery systems is frequently insufficient. The CPP-fused molecules tend to remain trapped inside endosomes and end up being degraded rather than delivered into the cytosol. One of the methods for endosomal escape of CPP-fused molecules is photochemical internalization (PCI), which is based on the use of light and a photosensitizer and relies on photoinduced endosomal membrane destabilization to release the cargo molecule. Currently, it remains unclear how this delivery strategy behaves after photostimulation. Recent findings, including our studies using CPP-cargo-photosensitizer conjugates, have shed light on the photoinduced endosomal escape mechanism. In this review, we discuss the structural design of CPP-photosensitizer and CPP-cargo-photosensitizer conjugates, and the PCI mechanism underlying their application.


Assuntos
Peptídeos Penetradores de Células/metabolismo , Sistemas de Liberação de Medicamentos , Endossomos/metabolismo , Substâncias Macromoleculares/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Peptídeos Penetradores de Células/química , Endocitose , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/metabolismo
7.
Int J Nanomedicine ; 15: 6749-6760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982231

RESUMO

Background: The combination of radiotherapy (RT) and chemotherapy, as a standard treatment for breast cancer in the clinic, is unsatisfactory due to chemoradioresistance and severe side effects. Methods and Results: To address these issues, a cancer cell-erythrocyte hybrid membrane-coated doxorubicin (DOX)-loaded gold nanocage (CM-EM-GNCs@DOX) was constructed for near-infrared light (NIR)-activated photothermal/radio/chemotherapy of breast cancer. CM-EM-GNCs@DOX inherited an excellent homologous target ability from the cancer cell membrane and an immune evasion capability from the erythrocyte membrane, together resulting in highly efficient accumulation in the tumor site with decreased clearance. Following the highly efficient uptake of CM-EM-GNCs@DOX in cancer cells, the RT efficacy was remarkably amplified due to the radiosensitization effect of CM-EM-GNCs@DOX, which reduced the needed radiotherapeutic dose. Importantly, with NIR irradiation, CM-EM-GNCs@DOX exerted a high photothermal effect, which not only ruptured CM-EM-GNCs@DOX to release DOX for precise and controllable chemotherapy, but also potentiated chemo/radiotherapy by photothermal therapy. Conclusion: Therefore, a highly efficient and safe combined photothermal/radio/chemotherapy approach was achieved in vitro and in vivo by CM-EM-GNCs@DOX, which provided a promising strategy for treating breast cancer.


Assuntos
Neoplasias da Mama/terapia , Membrana Celular/química , Doxorrubicina/administração & dosagem , Nanoestruturas/química , Fototerapia/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Membrana Eritrocítica/química , Feminino , Ouro/química , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Células MCF-7 , Fusão de Membrana , Camundongos , Camundongos Nus , Nanoestruturas/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
8.
PLoS One ; 15(9): e0239001, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915896

RESUMO

White-nose syndrome is a fungal disease responsible for the rapid decline of North American bat populations. This study addressed a novel method for inactivating Pseudogymnoascus destructans, the causative agent of WNS, using ultraviolet A (UVA) or B (UVB) radiation in combination with methoxsalen, a photosensitizer from the furanocoumarin family of compounds. Fungal spore suspensions were diluted in micromolar concentrations of methoxsalen (50-500 µM), then exposed to fixed doses of UVA radiation (500-5000 mJ/cm2), followed by plating on germination media. These plates were examined for two to four weeks for evidence of spore germination or inactivation, along with resultant growth or inhibition of P. destructans colonies. Pretreatment of fungal spores with low doses of methoxsalen resulted in a UVA dose-dependent inactivation of the P. destructans spores. All doses of methoxsalen paired with 500 mJ/cm2 of UVA led to an approximate two-log10 (~99%) reduction in spore viability, and when paired with 1000 mJ/cm2, a four-log10 or greater (>99.99%) reduction in spore viability was observed. Additionally, actively growing P. destructans colonies treated directly with methoxsalen and either UVA or UVB radiation demonstrated UV dose-dependent inhibition and termination of colony growth. This novel approach of using a photosensitizer in combination with UV radiation to control fungal growth may have broad, practical application in the future.


Assuntos
Ascomicetos/efeitos da radiação , Quirópteros/microbiologia , Metoxaleno/administração & dosagem , Micoses/veterinária , Fármacos Fotossensibilizantes/administração & dosagem , Terapia Ultravioleta , Animais , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/patogenicidade , Micoses/radioterapia , Esporos Fúngicos/patogenicidade , Esporos Fúngicos/efeitos da radiação , Síndrome
9.
AAPS PharmSciTech ; 21(6): 236, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32803351

RESUMO

In recent years, with the aging of the population and the frequent use of electronic devices, many eye diseases have shown a linear upward trend, such as dry eye disease, glaucoma, cataract, age-related macular degeneration, and diabetic retinopathy. These diseases are often chronic and difficult to cure. Based on the structure and barrier of the human eye, this review describes the pathogenesis and treatments of several intractable eye diseases and summarizes the advanced ocular drug delivery systems to provide new treatment ideas for these diseases. Finally, we also look forward to the prospect of RNAi therapy in the treatment of eye diseases.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/metabolismo , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Catarata/diagnóstico , Catarata/tratamento farmacológico , Catarata/metabolismo , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Oftalmopatias/diagnóstico , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Humanos , Latanoprosta/administração & dosagem , Latanoprosta/metabolismo , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Degeneração Macular/fisiopatologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/metabolismo , Timolol/administração & dosagem , Timolol/metabolismo , Resultado do Tratamento , Verteporfina/administração & dosagem , Verteporfina/metabolismo
10.
Photodiagnosis Photodyn Ther ; 31: 101889, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32592911

RESUMO

The corona virus pandemic has ignited a proliferation of research aimed at prevention of spread, early diagnosis and treatment. Coincidentally, in recent years the Yorkshire Laser Centre has been engaged in developing the methodology of applying PDT in chronic bronchiectasis. Our methodology is based on Methylene Blue (MB) mediated PDT used topically within the airway. The novelty of the method is the use of a nebulizer to deliver the photosensitizer. We suggest that our protocol and methodology could be modulated for use in respiratory infections of COVID -19.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Azul de Metileno/administração & dosagem , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Triazenos/administração & dosagem , Administração por Inalação , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pandemias , Seleção de Pacientes , Fármacos Fotossensibilizantes/administração & dosagem , Pneumonia Viral/diagnóstico , Síndrome Respiratória Aguda Grave/diagnóstico , Resultado do Tratamento
11.
Phys Med Biol ; 65(16): 165008, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32464613

RESUMO

Photodynamic therapy has been clinically proven to be effective, but its effect is limited to relatively shallow tumors because of its use of visible light. Radiodynamic therapy (RDT) has therefore been investigated as a means to treat deep-seated tumors. In this study, the treatment effect of a novel form of RDT consisting of radiation combined with 5-aminolevulinic acid (5-ALA) and carbamide peroxide was investigated using a mouse model. Male nude mice were injected bilaterally and subcutaneously with human prostate cancer (PC-3) cells and randomized into 8 treatment groups, consisting of various combinations of 15-MV radiotherapy (RT), 5-ALA, and carbamide peroxide. The treatment effect of a single fraction of treatment was measured by calculating tumor growth delay, monitored using weekly MR scans. The ability of the drugs to be delivered to the tumors was qualitatively measured using 18 F-FDG PET/CT scans. RDT was shown to significantly delay the tumor growth for the mouse model and tumor cell line investigated in this work. Tumors treated with RDT showed a decrease in tumor growth of 24 ± 9% and 21 ± 8% at one and two weeks post-treatment, respectively. Peroxide and 5-ALA did not contribute significantly to tumor growth delay when administered alone or separately with RT. Blood perfusion was shown to be able to deliver agents to the tumors investigated in this work, although uptake of 18 F-FDG was shown to be non-uniform.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Peróxido de Carbamida/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/terapia , Animais , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Cintilografia , Compostos Radiofarmacêuticos/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Nanomedicine ; 15: 2717-2732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368051

RESUMO

Background: Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis. Methods: In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation. Results: In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation. Conclusion: The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glioblastoma/terapia , Verde de Indocianina/administração & dosagem , Nanopartículas/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Fototerapia/métodos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Glioblastoma/patologia , Glicolipídeos/química , Humanos , Verde de Indocianina/química , Camundongos Nus , Micelas , Nanopartículas/química , Oligopeptídeos/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Curr Urol Rep ; 21(5): 19, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32248340

RESUMO

PURPOSE OF REVIEW: It has been firmly established that hexaminolevulinate-assisted blue light cystoscopy (HAL-BLC) reduces cancer recurrence rates. This review explores the impact of HAL-BLC on other meaningful outcomes in patients with bladder cancer, including disease progression, and earlier detection of disease at the time of surveillance cystoscopy. RECENT FINDINGS: A randomized clinical trial confirmed earlier implementation of HAL-BLC at the time of surveillance cystoscopy increased identification of cancerous lesions, including those of high grade, when compared with white light cystoscopy. In addition, the evidence is evolving that the use of HAL-BLC at the time of endoscopic treatment of high-risk tumors may lead to lower rates of progression to muscle invasion, and this in part may be due to better risk stratification leading to changes in treatment plan. The clinical contexts for the use of HAL-BLC are broader than prior knowledge. It is also becoming more clear that the positive impact of HAL-BLC is likely more than just reducing cancer recurrence rates, and patients would benefit from the technology at many time points in the management and follow-up of their disease.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Cistoscopia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Ácido Aminolevulínico/administração & dosagem , Progressão da Doença , Humanos , Luz , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
14.
Biol Pharm Bull ; 43(4): 736-741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32238716

RESUMO

Stimuli-responsive liposomes are promising drug carriers for cancer treatment because they enable controlled drug release and the maintenance of desired drug concentrations in tumor tissue. In particular, near-IR (NIR) light is a useful stimulus for triggering drug release from liposomes based on its advantages such as deep tissue penetration and safety. Previously, we found that a silicon phthalocyanine derivative, IR700, conjugated to antibodies, can induce the rupture of the cell membrane following irradiation by NIR light. Based on this finding, we constructed IR700-modified liposomes (IR700 liposomes) and evaluated their drug release properties triggered by NIR light. IR700 liposomes released substantial amounts of encapsulated calcein following irradiation by NIR light. Drug release was substantially suppressed by the addition of sodium azide, suggesting that liposomal membrane permeabilization was mediated by singlet oxygen generated from IR700. Moreover, calcein release from IR700 liposomes triggered by NIR light was promoted under conditions of deoxygenation and the presence of electron donors. Thus, membrane disruption should be induced by the physical change of IR700 from highly hydrophilic to hydrophobic as we previously described, although singlet oxygen can cause a certain level of membrane disruption under normoxia. We also observed that doxorubicin-encapsulated IR700 liposomes exhibited significant cytotoxic effects against CT-26 murine colon carcinoma cells following NIR light exposure. These results indicate that IR700 liposomes can efficiently release anti-cancer drugs following NIR light irradiation even under hypoxic conditions and, therefore, they would be useful for cancer treatment.


Assuntos
Portadores de Fármacos , Indóis , Fármacos Fotossensibilizantes , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/efeitos da radiação , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Fluoresceínas/administração & dosagem , Fluoresceínas/química , Humanos , Indóis/administração & dosagem , Indóis/química , Indóis/efeitos da radiação , Luz , Lipossomos , Camundongos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química
16.
Eur J Pharm Biopharm ; 149: 218-228, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32112893

RESUMO

Multidrug resistance (MDR) and the spread of cancer cells (metastasis) are major causes leading to failure of cancer treatment. MDR can develop in two main ways, with differences in their mechanisms for drug resistance, first drug-selected MDR developing after chemotherapeutic treatment, and metastasis-associated MDR acquired by cellular adaptation to microenvironmental changes during metastasis. This study aims to use a nanoparticle-mediated photodynamic therapy (NPs/PDT) approach to overcome both types of MDR. A photosensitizer, 5,10,15,20-Tetrakis(4-hydroxy-phenyl)-21H,23H-porphine (pTHPP) was loaded into poly(D,L-lactide-co-glycolide) (PLGA)-lipid hybrid nanoparticles. The photocytotoxic effect of the nanoparticles was evaluated using two different MDR models established from one cell line, A549 human lung adenocarcinoma, including (1) A549RT-eto, a MDR cell line derived from A549 cells by drug-selection, and (2) detachment-induced MDR acquired by A549 cells when cultured as floating cells under non-adherent conditions, which mimic metastasizing cancer cells in the blood/lymphatic circulation. In the drug-selected MDR model, A549RT-eto cells displayed 17.4- and 1.8-fold resistance to Etoposide and Paclitaxel, respectively, compared to the A549 parental cells. In contrast to treatment with anticancer drugs, NPs/PDT with pTHPP-loaded nanoparticles resulted in equal photocytotoxic effect in A549RT-eto and parental cells. Intracellular pTHPP accumulation and light-induced superoxide anion generation were observed at similar levels in the two cell lines. The NPs/PDT killed A549RT-eto and parental cells through apoptosis as revealed by flow cytometry. In the metastasis-associated MDR model, A549 floating cells exhibited resistance to Etoposide (11.6-fold) and Paclitaxel (57.8-fold) compared to A549 attached cells, but the floating cells failed to show resistance against the photocytotoxic effect of the NPs/PDT. The MDR overcoming activity of NPs/PDT is mainly due to delivery ability of the PLGA-lipid hybrid nanoparticles. In conclusion, this work suggests that PLGA-lipid hybrid nanoparticles have potential in delivering photosensitizer or chemotherapeutic drug for treating both drug-selected and metastasis-associated MDR lung cancer cells.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia/métodos , Células A549 , Adenocarcinoma de Pulmão/patologia , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/farmacologia , Humanos , Lipídeos/química , Neoplasias Pulmonares/patologia , Nanopartículas , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porfirinas/administração & dosagem
17.
Mo Med ; 117(1): 39-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158048

RESUMO

Maximal safe resection can improve patient outcomes for a variety of brain tumor types including low- and high-grade gliomas, pituitary adenomas, and other pathologies. Numerous intraoperative adjuncts exist to guide surgeons with maximizing extent of resection. Three distinct strategies exist including: 1) surgical navigation; 2) intraoperative imaging; and 3) tumor fluorescence. Surgical navigation involves registration of high-resolution three-dimensional imaging to the patient's cranial surface anatomy, allowing real-time localization of tumor and brain structures. Intraoperative imaging devices like intraoperative magnetic resonance imaging (iMRI), intraoperative computed tomography (iCT), 3-D fluoroscopy, and intraoperative ultrasonography (iUS) allow near real time visualization to assess the extent of resection. Intraoperative fluorescence via intravenous fluorescein or oral 5-aminolevulinic acid (5-ALA) causes brain tumors to "light up", which can be viewed through surgical optics using selective filters and specific wavelength light sources. A general overview, as well as implementation and utilization of some of these image guidance strategies at Washington University and by Siteman Cancer Center neurosurgeons at Barnes Jewish Hospital, is discussed in this review.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Imagem por Ressonância Magnética/métodos , Procedimentos Neurocirúrgicos/métodos , Ácido Aminolevulínico/administração & dosagem , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Fármacos Fotossensibilizantes/administração & dosagem , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X
18.
J Photochem Photobiol B ; 205: 111840, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146273

RESUMO

Unlike normal cells, cancer cells mutate to thrive in exaggerated levels of reactive oxygen species (ROS). This potentially makes them more susceptible to small molecule-induced oxidative stress. The intracellular ROS increase in cancer cells is a potential area under investigation for the development of cancer therapeutics targeting cancer cells. Visible photons of 430-490 nm wavelengths from a blue-light emitting diode (BLED) encompass the visible region of the spectrum known to induce ROS in cancer cells. Curcuminoids (CUR) naturally occurring photosensitizers sensitized by the blue wavelength of the visible light, well known for its potent anti-inflammatory and anticancer activity. Poor solubility and bioavailability, of the compound of the small molecule CUR restrict the therapeutic potential and limits CUR to be used as a photosensitizer. Here, our research group reports the use of small molecules CUR, encapsulated in liposome nanocarriers (LIP-CUR) coupled with blue light-emitting diode (BLED) induced photodynamic therapy (BLED-PDT). In A549 cancer cells in vitro, LIP-CUR coupled with BLED initiated BLED-PDT and triggered 1O2, ultimately resulting in caspase-3 activated apoptotic cell death. The combination of a non-cytotoxic dose of small molecule CUR co-treated with BLED to trigger BLED-PDT could be translated and be developed as a novel strategy for the treatment of cancer.


Assuntos
Diarileptanoides/administração & dosagem , Nanopartículas/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Células A549 , Apoptose/efeitos dos fármacos , Humanos , Luz , Lipossomos , Neoplasias/tratamento farmacológico
19.
Pharm Res ; 37(4): 72, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32215748

RESUMO

PURPOSE: Combination of PCI and chemotherapy represents a promising strategy for combating drug resistance of cancer. However, poor solubility of photosensitizers and unselectively released drugs at unwanted sites significantly impaired the treatment efficacy. Therefore, in the present study, we aimed to develop a nano-platform which could efficiently co-entrapping photosensitizers and chemotherapeutics for active targeting therapy of drug resistant cancers. METHODS: Two pro-drugs were respectively developed by covalently linking the Ce6 with each other via the GSH-sensitive linkage and the PTX with mPEG-PLA-COOH through the ROS sensitive-linker. The dual-responsive nanoparticles (PNP-Ce6) was developed by emulsion/solvent evaporation method and further modified with tLyp-1 peptides. Physicochemical properties of nanoparticles were determined by the TEM and DLC. Cellular uptake assay was investigated with the Ce6 acting as the fluorescent probe and cell growth was studied by the MTT experiment. In vivo tumor targeting and anti-tumor assay was investigated on the colorectal cancer-bearing mice. RESULTS: The developed tPNP-Ce6 were stable enough under the normal physiological conditions. However, free Ce6 and PTX were completely released when exposed the tPNP-Ce6 to the redox environment. Excellent tumor-targeting drug delivery was achieved by the tPNP-Ce6, which in turn resulted in satisfactory anit-tumor effect. Of great importance, super inhibition effect on tumor progress was achieved by the combination therapy when compared with the group only received with chemotherapy.. CONCLUSION: The results obtained in the present study indicated that the developed tPNP-Ce6 may have great potential in enhancing the therapeutic efficacy of drug-resistant colorectal cancer. Graphical Abstract Left: Targeting delivery of drug to tumor site by the tumor recognizable and dual-responsive nanoparticles and penetrating into tumor inner via the mediation of irradiation. Right: Nanoparticle distribution within tumor tissues with green represents the blood vessels stained with CD31, blue signal represents the cell nuclei stained with DAPI and red shows fluorescence of Ce6 as the indicator of the nanoparticles.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Nanopartículas , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/administração & dosagem , Pró-Fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Drug Deliv ; 27(1): 378-386, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32098528

RESUMO

Despite the excellent efficacy and low toxicity of photoresponse therapy, which has attracted considerable attention for use in non-small cell lung cancer (NSCLC) therapy, unsatisfactory cellular permeability, and instability, both in vitro and in vivo have limited further clinical applications of indole cyanine photosensitizers. Here, we explore the supramolecular self-assembly of a 'hyalurosome' that is mediated by calcium phosphate nanonuclei. Through hyaluronate-mediated CD44 targeting, the constructed hyalurosome specifically delivers ICG into NSCLC cells and then induces severe hyperthermia accompanied by the generation of singlet oxygen upon photoirradiation. In contrast to the action of the native form, indocyanine green encapsulated in a hyalurosome showed significantly increased cellular endocytosis and inhibited cell proliferation both in vitro and in vivo. Our study indicated that this hyalurosome is a promising candidate for the targeted delivery of photosensitizers, which may be useful in NSCLC therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Ácido Hialurônico/química , Neoplasias Pulmonares/terapia , Fototerapia/métodos , Células A549 , Animais , Fosfatos de Cálcio/química , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Hipertermia Induzida/métodos , Verde de Indocianina/administração & dosagem , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
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