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1.
Nanotechnology ; 33(23)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35193121

RESUMO

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2µM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Células Endoteliais/patologia , Feminino , Glutationa , Humanos , Isoquinolinas , Nanopartículas/química , Fármacos Fotossensibilizantes , Porfirinas/química , Pirazóis , Pirimidinas
2.
Int J Nanomedicine ; 17: 3821-3839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072959

RESUMO

Introduction: During the combined treatment of tumors, the non-interfering transportation of drugs with different solubilities and the controllable sequential release are the main challenges. Here, we reported a double-chamber "Dandelion" -like sequential drug delivery system to realize the sequential release of different drugs for treating malignant tumors synergistically. Methods: After synthesizing mesoporous silica nanoparticles (MSN) by template method, a hydrophilic chemotherapy drug doxorubicin (DOX) was loaded into the channels of mesoporous silica (MSN) and locked with polydopamine (PDA) coating. Next, ß-cyclodextrin (ß-CDs) was decorated on PDA by Michael addition reaction, and the hydrophobic photosensitizer chlorin e6 (Ce6) was encapsulated into the hydrophobic chambers of ß-CDs. Finally, AS1411 was modified on the surface of PDA and obtained DOX@MSN@PDA-ß-CD/Ce6-AS1411 nanoparticles (DMPCCA) through which orthogonal loading and effective controlled release of different drugs were realized. Results: Under the sequential irradiations of 808 nm and 660 nm near-infrared (NIR) laser, PDA promoted the extensive release of Ce6 firstly while playing the effect of photothermal therapy (PTT), further to achieve the effect of photodynamic therapy (PDT) of Ce6. Meanwhile, the rapid release of DOX loaded in MSN channels showed a time lag of about 5 h after Ce6 release, through which it maximized the chemotherapeutic effect. Besides, the present drug loading nano-platform combined passive tumor-targeting effect given by EPR and active tumor-targeting effect endowed by AS1411 realized PTT-PDT-chemotherapy triple mode synergistic combination. Conclusion: We offer a general solution to address the key limitations for the delivery and sequential release of different drugs with different solubilities.


Assuntos
Neoplasias , Fotoquimioterapia , Taraxacum , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Neoplasias/terapia , Dióxido de Silício/química
3.
Orv Hetil ; 163(36): 1422-1429, 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36057871

RESUMO

INTRODUCTION: Photodynamic therapy is indicated for the treatment of superficial basal cell carcinoma, Bowen's disease and actinic keratosis. Reactive oxygen radicals are released from the metabolite of the topically applied photosensitizer that is excited by light, which selectively leads to the destruction of tumor cells. The procedure can be performed with an artificial light source or with the use of sunlight. The latter is called daylight photodynamic therapy, which is an effective and painless procedure. OBJECTIVE: Our aim was to introduce daylight photodynamic therapy in actinic keratoses at our department and to optimize the treatment protocol for the local climatic conditions. METHOD: Three clinical trials were performed. The difference between the treatment protocols was between the incubation time of the photosensitizer on the skin and in the time patients spent under the sunlight. RESULTS: When using the international treatment protocol, 73% of the actinic keratoses showed complete, while 27% partial remission. By reducing the proportion of time patients spent outdoor, complete remission was achieved in two-thirds and partial remission in one-third of the lesions. At doses above 100 J/cm², severe erythema was observed 24 hours after the treatment. To avoid this, we calculated the time to be spent outdoor by dosimetry. Partial remission was achieved in 15%, complete remission in 85% of the actinic keratoses with good tolerability. DISCUSSION: The stepwise modification of the treatment protocol resulted in an effective and well-tolerated treatment in actinic keratoses under the local climatic conditions. CONCLUSION: The method has been successfully adapted in our clinic and is used in daily practice to treat actinic keratoses. Orv Hetil. 2022; 163(36): 1422-1429.


Assuntos
Ceratose Actínica , Melanoma , Fotoquimioterapia , Neoplasias Cutâneas , Humanos , Ceratose Actínica/tratamento farmacológico , Ceratose Actínica/patologia , Melanoma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
4.
Int J Nanomedicine ; 17: 3777-3792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065288

RESUMO

Background: Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis. Methods: A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC). Results: The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs. Conclusion: This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fotoquimioterapia , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Verde de Indocianina/farmacologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Camundongos , Fototerapia/métodos , Terapia Fototérmica , Nanomedicina Teranóstica/métodos
5.
J Photochem Photobiol B ; 234: 112510, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36049287

RESUMO

Each year a rising number of infections can not be successfully treated owing to the increasing pandemic of antibiotic resistant pathogens. The global shortage of innovative antibiotics fuels the emergence and spread of drug resistant microbes. Basic research, development, and applications of alternative therapies are urgently needed. Since the 90´s, light-mediated therapies have promised to be the next frontier combating multidrug-resistance microbes. These platforms have demonstrated to be a reliable, rapid, and efficient alternative to eliminate tenacious pathogens while avoiding the emergence of resistance mechanisms. Among the materials showing antimicrobial activity triggered by light, conjugated polymers (CPs) have risen as the most promising option to tackle this complex situation. These materials present outstanding characteristics such as high absorption coefficients, great photostability, easy processability, low cytotoxicity, among others, turning them into a powerful class of photosensitizer (PS)/photothermal agent (PTA) materials. Herein, we summarize and discuss the advances in the field of CPs with applications in photodynamic inactivation and photothermal therapy towards bacteria elimination. Additionally, a section of current challenges and needs in terms of well-defined benchmark experiments and conditions to evaluate the efficiency of phototherapies is presented.


Assuntos
Fotoquimioterapia , Polímeros , Antibacterianos , Bactérias , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Polímeros/farmacologia
6.
Biomed Pharmacother ; 153: 113506, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076595

RESUMO

As the sixth leading cause of cancer death, esophageal cancer is threatening the life of people worldwide. Traditional treatments, such as surgery, chemotherapy, radiotherapy, are facing always augmented challenges including invasion, multidrug resistance (MDR), off-target toxicity. Chemo & Photodynamic synergistic therapy represents one promising strategy for improved treatment efficiency. But it is still hindered by the lack of tumor targeting, deleterious side effects, and unfavorable microenvironment for photodynamic therapy (PDT). To overcome those obstacles, one theranostic nano-assambly drug, GCDs-Ce6/Pt-EGF, was designed and fabricated. Green fluorescence carbon dots (GCDs) with the excellent optical properties, modifiability and low toxicity were prepared as drug carrier. Epidermal growth factor (EGF) was conjugated to the nano-assembly to realize tumor specific targeting. Chlorin e6 (Ce6) in the presence of laser irradiation achieved PDT by generating proapoptosis reactive oxygen species (ROS). Moreover, Ce6 incorporated into GCDs endowed the nano-assambly imaging ability and facilitate image-guided therapy. Pt(IV), cisplatin prodrug, in the nano-assambly depleted the glutathione (GSH) of tumor microenvironment when it was reduced to cytotoxicity Pt(II). Compared with single treatment, GCDs-Ce6/Pt-EGF exhibited enhanced tumor cell killing capacity and better biosafety in vitro and in vivo, especially for EGFR bearing tumor. It paved ways for developing novel theranostic agent to be potentially applied in clinic.


Assuntos
Clorofilídeos , Neoplasias Esofágicas , Nanopartículas , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Fator de Crescimento Epidérmico , Neoplasias Esofágicas/tratamento farmacológico , Glutationa , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Medicina de Precisão , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
7.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076920

RESUMO

Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, the highly aromatic Pc core leads to undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A3B type asymmetric Pc photosensitizers (PSs) were designed in order to decrease aggregation and increase the aqueous solubility. Here we report the synthesis, characterization, optical properties, cellular localization, and cytotoxicity of three novel Pc-based agents (LC31, MLC31, and DMLC31Pt). The stepwise functionalization of the peripheral moieties has a strong effect on the distribution coefficient (logP), cellular uptake, and localization, as well as photocytotoxicity. Additional experiments have revealed that the presence of the malonic ester moiety in the reported agent series is indispensable in order to induce photocytotoxicity. The best-performing agent, MLC31, showed mitochondrial targeting and an impressive phototoxic index (p.i.) of 748 in the cisplatin-resistant A2780/CP70 cell line, after a low-dose irradiation of 6.95 J/cm2. This is the result of a high photocytotoxicity (IC50 = 157 nM) upon irradiation with near-infrared (NIR) light, and virtually no toxicity in the dark (IC50 = 117 µM). Photocytotoxicity was subsequently determined under hypoxic conditions. Additionally, a preliminarily pathway investigation of the mitochondrial membrane potential (MMP) disruption and induction of apoptosis by MLC31 was carried out. Our results underline how agent design involving both hydrophilic and lipophilic peripheral groups may serve as an effective way to improve the PDT efficiency of highly aromatic PSs for NIR light-mediated cancer therapy.


Assuntos
Neoplasias Ovarianas , Fotoquimioterapia , Linhagem Celular Tumoral , Feminino , Humanos , Mitocôndrias , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Triazenos
8.
Molecules ; 27(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36080406

RESUMO

Ruthenium-based complexes represent a new frontier in light-mediated therapeutic strategies against cancer. Here, a density functional-theory-based computational investigation, of the photophysical properties of a conjugate BODIPY-Ru(II) complex, is presented. Such a complex was reported to be a good photosensitizer for photodynamic therapy (PDT), successfully integrating the qualities of a NIR-absorbing distyryl-BODIPY dye and a PDT-active [Ru(bpy)3]2+ moiety. Therefore, the behaviour of the conjugate BODIPY-Ru(II) complex was compared with those of the metal-free BODIPY chromophore and the Ru(II) complex. Absorptions spectra, excitation energies of both singlet and triplet states as well as spin-orbit-matrix elements (SOCs) were used to rationalise the experimentally observed different activities of the three potential chromophores. The outcomes evidence a limited participation of the Ru moiety in the ISC processes that justifies the small SOCs obtained for the conjugate. A plausible explanation was provided combining the computational results with the experimental evidences.


Assuntos
Fotoquimioterapia , Rutênio , Compostos de Boro , Fármacos Fotossensibilizantes/farmacologia
9.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077239

RESUMO

Psoriasis (PS) is an immune-mediated skin disease with substantial negative effects on patient quality of life. Despite significant progress in the development of novel treatment options over the past few decades, a high percentage of patients with psoriasis remain undertreated and require new medications with superior long-term efficacy and safety. One of the most promising treatment options against psoriatic lesions is a form of phototherapy known as photodynamic therapy (PDT), which involves either the systemic or local application of a cell-targeting photosensitizing compound, followed by selective illumination of the lesion with visible light. However, the effectiveness of clinically incorporated photosensitizers in psoriasis treatment is limited, and adverse effects such as pain or burning sensations are frequently reported. In this study, we performed a literature review and attempted to provide a pooled estimate of the efficacy and short-term safety of targeted PDT in the treatment of psoriasis. Despite some encouraging results, PDT remains clinically underutilized. This highlights the need for further studies that will aim to evaluate the efficacy of a wider spectrum of photosensitizers and the potential of nanotechnology in psoriasis treatment.


Assuntos
Fotoquimioterapia , Psoríase , Humanos , Nanotecnologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/patologia , Qualidade de Vida
10.
J Nanobiotechnology ; 20(1): 410, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109814

RESUMO

Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H2O2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.


Assuntos
DNA Catalítico , Ferroptose , Fotoquimioterapia , Porfirinas , Catalase , DNA , Glutationa/metabolismo , Hemina , Humanos , Peróxido de Hidrogênio , Hipóxia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia , Ferro , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Porfirinas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Triazenos
11.
J Clin Pediatr Dent ; 46(4): 287-292, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099227

RESUMO

How patients perceive impact of diseases is an essential component when characterising different disease impacts, and effects of dental treatments should be perceived by the patients. This study aimed to assess the impact of conservative treatment of deep caries lesions using the selective caries removal (SCR) associated to a low laser therapy (antimicrobial photodynamic therapy-aPDT) on oral health-related quality of life (OHRQoL). STUDY DESIGN: A non-randomized clinical before-and-after study was conducted on children aged 4 to 8 years. The data was obtained applying the Brazilian version of the Early Childhood Oral Health Impact Scale (ECOHIS) to the caretakers in an interview before and after treatment. The paired T-student test considering p<0.05 and the treatment responsiveness detecting the effect size by means of standardized response mean (SRM) was evaluated. RESULTS: The mean impact on OHRQoL on the total scale was 5.46 ± 4.54 for before and 2.42 ± 3.54 for after treatment (p<0.01). The ECOHIS demonstrated satisfatory longitudinal responsiveness except for psychological, self-image/social interaction and Family function domain (SRM<0.5). CONCLUSION: This study demonstrated that the association of a low laser therapy (aPDT) with SCR did not influence negatively on OHRQoL. In the practice of pediatric dentistry, this conservative dental treatment improved the OHRQoL after 3 months of follow up.


Assuntos
Anti-Infecciosos , Cárie Dentária , Fotoquimioterapia , Criança , Pré-Escolar , Assistência Odontológica , Cárie Dentária/psicologia , Cárie Dentária/terapia , Suscetibilidade à Cárie Dentária , Humanos , Qualidade de Vida
12.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077451

RESUMO

This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1H and 13C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up to 0.54. The photodynamic activity was tested using bladder (5637), prostate (LNCaP), and melanoma (A375) cancer cell lines. In vitro experiments clearly showed the structure-activity relationship regarding types of substituents, their positions in the phenyl ring, and the variety of central metal ions on the porphyrin core. Notably, the metal-free derivative 3 and its zinc derivative 6 exerted strong cytotoxic activity toward 5637 cells, with IC50 values of 8 and 15 nM, respectively. None of the tested compounds induced a cytotoxic effect without irradiation. In conclusion, these results highlight the potential value of the tested compounds for PDT application.


Assuntos
Antineoplásicos , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fotoquímica , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Porfirinas/química , Zinco/farmacologia
13.
Int J Mol Sci ; 23(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36077597

RESUMO

Over the past 30 years, photodynamic therapy (PDT) has shown great development. In the clinical setting the few approved molecules belong almost exclusively to the porphyrin family; but in the scientific field, in recent years many researchers have been interested in other families of photosensitizers, among which BODIPY has shown particular interest. BODIPY is the acronym for 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene, and is a family of molecules well-known for their properties in the field of imaging. In order for these molecules to be used in PDT, a structural modification is necessary which involves the introduction of heavy atoms, such as bromine and iodine, in the beta positions of the pyrrole ring; this change favors the intersystem crossing, and increases the 1O2 yield. This mini review focused on a series of structural changes made to BODIPYs to further increase 1O2 production and bioavailability by improving cell targeting or photoactivity efficiency.


Assuntos
Fotoquimioterapia , Compostos de Boro/química , Compostos de Boro/uso terapêutico , Corantes Fluorescentes/química , Triazenos
14.
Biomaterials ; 288: 121700, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36049897

RESUMO

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was "double-locked" by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the "double-key", which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.


Assuntos
Clorofilídeos , Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/tratamento farmacológico , Oxirredução , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Porfirinas/química , Microambiente Tumoral
15.
Molecules ; 27(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014325

RESUMO

Photodynamic therapy (PDT) is a minimally invasive, alternative, and promising treatment for various diseases, including cancer, actinic keratosis, Bowen's disease, macular degeneration, and atherosclerotic plaques. PDT involves three different components, photosensitizers (PS), molecular oxygen, and light. The photoactivation of administered PSs using a specific wavelength of light in the presence of molecular oxygen leads to the generation of reactive oxygen species that leads to tumour cell death. Photosensitizing potentials of many commercially available compounds have been reported earlier. However, the possibilities of PDT using herbal medicines, which contain many photosensitizing phytochemicals, are not much explored. Medicinal plants with complex phytochemical compound mixtures have the benefit over single compounds or molecules in the treatment of many diseases with the benefit of low or reduced toxic side effects. This review emphasizes the role of various herbal medicines either alone or in combination to enhance the therapeutic outcome of photodynamic therapy.


Assuntos
Ceratose Actínica , Fotoquimioterapia , Neoplasias Cutâneas , Humanos , Ceratose Actínica/tratamento farmacológico , Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico
17.
Cell Mol Biol (Noisy-le-grand) ; 68(5): 72-76, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36029513

RESUMO

This study was performed to evaluate the histological changes in the cornea after accelerated collagen crosslinking. In this regard, the right eyes of 7 New Zealand albino rabbits weighing 1.5 to 2 kg were studied. The right eye was considered the case group, and the left eye was considered the control group. The right eye epithelium was removed, riboflavin 0.1 solutions (10 mg riboflavin-5 phosphate in 10 ml dextran-T-500, 20%) were shaken every three minutes for 30 minutes and exposed to UVA for 10 minutes, and crosslinking was performed. All rabbits were euthanized and histologically evaluated. Apoptosis was assessed using the tunnel method. The results showed a significant difference in the mean percentage of apoptotic cells in the treatment and control groups. In both endothelial cells and keratocytes in the treated cornea, the number of apoptotic cells was significantly higher than in the control group. In the general examination of the cornea (keratocytes and endothelium) in the right eye of rabbits, the mean and standard deviation of the percentage of apoptotic cells was 18.39 ± 3.4 and in the left eye was 6.37 ± 1.8. The apoptosis results of keratocytes in the right eye showed that the mean and standard deviation for the percentage of apoptotic keratocytes was 2.86 ± 1.07, which was significantly higher than in the left eye (0.53 ± 0.43) (P <0.001). The mean and standard deviation of endothelial apoptotic cells in the right and left eyes were 86.2 and 53.5, respectively, statistically significant (P = 0.026). Although CXL is a reliable method of preventing the progression of keratoconus disease, there is still a risk of endothelial cell damage and related complications due to endothelial cell damage, and further studies are needed.


Assuntos
Ceratocone , Fotoquimioterapia , Animais , Colágeno , Córnea , Reagentes de Ligações Cruzadas , Células Endoteliais , Fármacos Fotossensibilizantes , Coelhos , Riboflavina , Raios Ultravioleta
18.
Proc Natl Acad Sci U S A ; 119(34): e2210504119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969782

RESUMO

Elucidating the underlying photochemical mechanisms of action (MoA) of photodynamic therapy (PDT) may allow its efficacy to be improved and could set the stage for the development of new classes of PDT photosensitizers. Here, we provide evidence that "photoredox catalysis in cells," wherein key electron transport pathways are disrupted, could constitute a general MoA associated with PDT. Taking the cellular electron donor nicotinamide adenine dinucleotide as an example, we have found that well-known photosensitizers, such as Rose Bengal, BODIPY, phenoselenazinium, phthalocyanine, and porphyrin derivatives, are able to catalyze its conversion to NAD+. This MoA stands in contrast to conventional type I and type II photoactivation mechanisms involving electron and energy transfer, respectively. A newly designed molecular targeting photocatalyst (termed CatER) was designed to test the utility of this mechanism-based approach to photosensitizer development. Photoexcitation of CatER induces cell pyroptosis via the caspase 3/GSDME pathway. Specific epidermal growth factor receptor positive cancer cell recognition, high signal-to-background ratio tumor imaging (SBRTI = 12.2), and good tumor growth inhibition (TGI = 77.1%) are all hallmarks of CatER. CatER thus constitutes an effective near-infrared pyroptotic cell death photo-inducer. We believe the present results will provide the foundation for the synthesis of yet-improved phototherapeutic agents that incorporate photocatalytic chemistry into their molecular design.


Assuntos
Antineoplásicos , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia
19.
J Nanobiotechnology ; 20(1): 385, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999549

RESUMO

BACKGROUND: Exosomes are recognized as effective platforms for targeted delivery for their high physicochemical stability and biocompatibility. However, most of the exosomes are inevitably and rapidly cleared by mononuclear phagocytic system (MPS) during cancer therapy. How to engineer exosome to enhance the delivery efficiency is being intensively explored. In this study, we have constructed mPEG2000-TK-CP05 decorated exosomes as effective delivery platforms to achieve enhanced photodynamic/chemical cancer therapy. RESULTS: Exosomes were coated with CP05-TK-mPEG2000, in which CP05 is a peptide with high affinity to exosomal CD63 and TK could be cleaved by ROS. The resulted exosomes, namely stealth Exo, were electroporated to load RB (photosensitizer Rose Bengal) and Dox (Doxorubicin). We verified that the Stealth Exo@RB (Stealth Exo additionally loaded with RB) could escape MPS while accumulate in the tumor region efficiently in the xenograft model when laser irradiation conducted locally. Additionally, we revealed that the Stealth Exo serves as an efficient platform for Dox delivery. Dox, together with the RB mediated photodynamic therapy induce tumor cell damage synergistically in the tumor region. Moreover, the proposed switchable stealth exosomes minimized the dose of toxic Dox and thus allowed robust tumor immune response. CONCLUSIONS: Our results indicated that the proposed Stealth Exo greatly improves both the accessibility and efficiency of drug delivery, with minimal chemical or genetic engineering. The proposed Stealth Exo serve as a promising and powerful drug delivery nanoplatform in cancer treatment.


Assuntos
Exossomos , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio
20.
World J Surg Oncol ; 20(1): 265, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35999574

RESUMO

BACKGROUND: There are no guidelines for straightforwardly managing advanced lung cancer (T3 or T4). Although surgery has traditionally been regarded as the mainstay treatment and the only curative modality, it has limited relevance for patients with locally advanced non-small cell lung cancer (NSCLC). Photodynamic therapy (PDT) is a clinically approved cancer therapy; it is an established treatment modality with curative intent for early-stage and superficial endobronchial lesions. However, the efficacy of PDT in advanced lung cancer is controversial, and it has primarily been used in palliative care. CASE PRESENTATION: This case report describes a 70-year-old male who had right upper lung cancer and an endobronchial lesion that extended into the distal trachea. A biopsy specimen was obtained upon bronchoscopy, and the result confirmed squamous cell carcinoma. We performed a definitive sleeve lobectomy and intraoperative PDT. Gross total resection of the tumor was achieved, but the presence of microscopic residual tumors was inevitable. Complete anatomical resection of the primary tumor by pneumonectomy was not possible due to poor lung function and endobronchial extension to the distal trachea. We decided to apply intraoperative PDT to the lumen and outer wall of the bronchi and distal trachea for local tumor control. The patient is alive with no evidence of disease after 13 months of follow-up. CONCLUSIONS: This is the first report to describe the feasibility and efficacy of intraoperative PDT as part of multimodal therapy for locally advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fotoquimioterapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Pneumonectomia
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