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1.
Yakugaku Zasshi ; 140(10): 1243-1249, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999203

RESUMO

Here the author describes the tumor-selective delivery of a fluorescence photosensitizing agent and an antitumor agent, based on the polymer effect of an N-(2-hydroxypropyl)methacrylamide (HPMA) based copolymer, by utilizing the enhanced permeability and retention (EPR) effect seen in solid tumors. Firstly, the tumor distribution of the photosensitizer, zinc-protoporphyrin IX (ZnPP), was significantly increased by conjugation with the HPMA polymer (P-ZnPP). The P-ZnPP suppressed tumor growth by local generation of cytotoxic singlet oxygen, and the tumor tissue was visualized by fluorescence upon light irradiation. Subsequently, a two-step mechanism for tumor selectivity was observed for the cytotoxic anthracycline, pirarubicin (THP), which conjugated the HPMA-based copolymer via a hydrazone bond (P-THP). The EPR-dependent accumulation of P-THP and the tumor-selective release of THP in the tumor tissues led to highly tumor-selective toxicity. Rapid cell uptake of THP compared to other anthracyclines, and deeper P-THP penetration of the tumor cell spheroid were attributed to the superior antitumor activity of P-THP. The molecular weight of P-THP affected its antitumor activity; oligomeric P-THP derivatives with higher molecular weights, DP-THP and SP-THP, showed even higher antitumor activity. P-THP was effective for both implanted tumor and autochthonous tumor models. These results indicate that nano-sized anticancer drugs based on polymer effect are promising clinical therapeutics.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Fármacos Fotossensibilizantes , Polímeros , Protoporfirinas , Animais , Antraciclinas/química , Antraciclinas/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Metacrilatos/química , Terapia de Alvo Molecular , Peso Molecular , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/metabolismo , Protoporfirinas/química , Protoporfirinas/metabolismo
2.
Molecules ; 25(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977525

RESUMO

The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10-15 years in order to identify the most promising areas.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Porfirinas/farmacologia , Antivirais/química , Humanos , Indóis/química , Indóis/farmacologia , Pandemias , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Ligação Viral/efeitos dos fármacos
3.
Int J Nanomedicine ; 15: 5459-5471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801700

RESUMO

Purpose: Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. Methods and Results: PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG ("PEG-BSA-AgNP/ICG"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. Conclusion: Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Difusão Dinâmica da Luz , Meia-Vida , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Melanoma Experimental/tratamento farmacológico , Camundongos Endogâmicos ICR , Camundongos Nus , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/química , Soroalbumina Bovina/química , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Cell Prolif ; 53(4): e12786, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32301195

RESUMO

OBJECTIVES: Photodynamic therapy (PDT) is a novel non-invasive therapeutic method, which has been widely applied for the treatment of human oral cancers. However, the problems of undesirable singlet oxygen (1 O2 ) quantum yields and long-term phototoxicity were inevitable during the application of traditional photosensitizers. Therefore, it is necessary to explore novel photosensitizers for the improvement of therapeutic effects. In our study, the sulphur-doped carbon dots (S-CDs) of high yield of singlet oxygen (1 O2 ) were synthesized as a nano-photosensitizer for OSCC to improve the PDT efficacy in clinical practice. MATERIALS AND METHODS: After synthesis of the novel S-CDs, the size, morphologic characteristics, surface potential and yield of singlet oxygen (1 O2 ) were determined. In vitro study was performed to compare the therapeutic effect as well as the biocompatibility of the novel S-CDs to those of 5-ALA. Besides, possible mechanism of action was illustrated. RESULTS: After synthesis of the novel S-CDs, the size, morphologic characteristics, surface potential and yield of singlet oxygen (1 O2 ) were determined. In vitro study was performed to compare the therapeutic effect as well as the biocompatibility of the novel S-CDs to those of 5-ALA. Besides, possible mechanism of action was illustrated. CONCLUSIONS: These data from the in vitro study demonstrated the promising safety profile of the low dose (nmol/L) S-CDs, which indicated the novel S-CDs could be used as a promising photodynamic agent for oral cancer therapy.


Assuntos
Carbono/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Enxofre/farmacologia , Apoptose/efeitos dos fármacos , Carbono/química , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Humanos , Modelos Moleculares , Neoplasias Bucais/patologia , Nanopartículas/química , Nanopartículas/ultraestrutura , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Enxofre/química
5.
Chemistry ; 26(34): 7685-7691, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32294275

RESUMO

Photodynamic therapy (PDT) is a promising alternative treatment for different types of cancer due to its high selectivity, which prevents healthy tissues from being damaged. The use of nanomaterials in PDT has several advantages over classical photosensitizing agents, due to their unique properties and their capacity for functionalization. Especially interesting is the use of metallic nanoparticles, which are capable of absorbing electromagnetic radiation and either transferring this energy to oxygen molecules for the generation of reactive oxygen species (ROS) or dissipating it as heat. Although previous reports have demonstrated the capacity of Rh derivatives to serve as anti-tumor drugs, to the best of our knowledge there have been no studies on the potential use of small-sized Rh nanoparticles as photosensitizers in PDT. In this study, 5 nm Rh nanoparticles have been synthesized and their potential in PDT has been evaluated. The results show that treatment with Rh nanoparticles followed by NIR irradiation induces apoptosis in cancer cells through a p53-independent mechanism.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/química , Ródio/farmacologia , Apoptose , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes/química , Ródio/química
6.
J Photochem Photobiol B ; 204: 111808, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006892

RESUMO

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Alumínio/química , Neoplasias da Mama/tratamento farmacológico , Indóis/química , Neoplasias Pulmonares/tratamento farmacológico , Nanoestruturas/química , Fármacos Fotossensibilizantes/uso terapêutico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/uso terapêutico , Nanoestruturas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transplante Homólogo , Microtomografia por Raio-X
7.
Top Curr Chem (Cham) ; 378(2): 21, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030541

RESUMO

DNA nanostructures hold great promise for various applications due to their remarkable properties, including programmable assembly, nanometric positional precision, and dynamic structural control. The past few decades have seen the development of various kinds of DNA nanostructures that can be employed as useful tools in fields such as chemistry, materials, biology, and medicine. Aptamers are short single-stranded nucleic acids that bind to specific targets with excellent selectivity and high affinity and play critical roles in molecular recognition. Recently, many attempts have been made to integrate aptamers with DNA nanostructures for a range of biological applications. This review starts with an introduction to the features of aptamer-functionalized DNA nanostructures. The discussion then focuses on recent progress (particularly during the last five years) in the applications of these nanostructures in areas such as biosensing, bioimaging, cancer therapy, and biophysics. Finally, challenges involved in the practical application of aptamer-functionalized DNA nanostructures are discussed, and perspectives on future directions for research into and applications of aptamer-functionalized DNA nanostructures are provided.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA/química , Nanoestruturas/química , Técnicas Eletroquímicas , Terapia Genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
8.
Int J Nanomedicine ; 15: 137-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021170

RESUMO

Purpose: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. Methods: In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Melanoma Experimental/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Indóis/administração & dosagem , Indóis/química , Lasers , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polímeros/química , Oxigênio Singlete/farmacocinética , Sulfetos/química
9.
Int J Nanomedicine ; 15: 151-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021171

RESUMO

Purpose: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance. Patients and Methods: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted ß-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN). Results: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection. Conclusion: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Feminino , Humanos , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Camundongos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Albumina Sérica Humana/química
10.
World J Microbiol Biotechnol ; 36(2): 31, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048066

RESUMO

Biogenic production of nanoparticles is eco-friendly, less expensive method with various medical and biological applications. Nanotechnology along with photodynamic therapy is gaining tremendous importance with enhanced efficacy. The present work was aimed to evaluate methanolic extracts and nanoparticles of two selected plants (Datura suavolens and Verbina tenuisecta) for cytotoxic photodynamic, antioxidant and antimicrobial study. Both extract and silver (5 mM) nanoparticles of Datura plant showed significant activities against bacterial strains. Maximum ZOI of 27.3 ± 1.6 mm was observed with nanoparticles of Datura branches with minimum inhibitory (MIC) value of 32 µg/ml. In case of antifungal and antioxidant assay samples were moderately active. Silver nanoparticles and extracts were effective against rhabdomyosarcoma cell line with lowest IC50 value of 42.5 ± 0.6 µg/ml and percent viability of 25.6 ± 1.3 of Verbena tenuisecta. However, nanoparticles of Datura leaves and branches were more potent with IC50 value of 2.4 ± 0.9 µg/ml and 7.8 ± 1.1 µg/ml respectively. The result of photodynamic study showed that efficacy of photosensitizer was enhanced and percent viability reduced when nanoparticles used as an adjunct. The color change and UV spectra (415‒425 nm) indicated the production of nanoparticles. Fourier transform infrared spectroscopy (FTIR) spectra showed presence of different functional groups e.g., hydroxyl, carbonyl and amino. Nanoparticles are sphenoid in morphology and size ranges between 20-150 nm. Current study showed these silver nanoparticles can be used as cytotoxic agent in photodynamic therapy and can play a critical role to establish medicinal potential of selected plants.


Assuntos
Datura/química , Metanol/farmacologia , Prata/farmacologia , Verbena/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas , Metanol/química , Metanol/isolamento & purificação , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/isolamento & purificação , Fármacos Fotossensibilizantes/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Prata/química , Prata/isolamento & purificação
11.
Chem Pharm Bull (Tokyo) ; 68(2): 150-154, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009082

RESUMO

Singlet oxygen (1O2) is highly oxidative and exerts strong cytotoxic effects. We tried to establish the best combination of a singlet oxygen generation system and a detection method with ESR, for measurement of the quenching activities of various substances. The photosensitizing reaction of rose bengal or thermal decomposition of 4-methyl-1,4-etheno-2,3-benzodioxin-1(4H)-propanoic acid (endoperoxide, EP) was used for the generation of 1O2, and a sterically hindered secondary amine, 2,2,6,6-tetramethyl-4-piperidone (TEMPD) or 2,2,6,6-tetramethyl-4-piperidinol (TEMP-OH), was used as the 1O2 detection probe. These secondary amines were oxidized by 1O2 to form stable nitroxide radicals, which were detectable by ESR. TEMPD was found to be readily oxidized by air, causing large background signals in comparison with TEMP-OH. The ESR signal obtained by the irradiation of rose bengal with visible light in the presence of TEMP-OH consisted of two kinds of nitroxide radical overlapping. In contrast, only a single nitroxide signal was observed when TEMP-OH was reacted with 1O2 generated from EP. Therefore, the best combination should be EP as the 1O2 generator and TEMP-OH as the detection probe. When using this combination, we found that the concentrations of some organic solvents such as dimethyl sulfoxide and acetonitrile should be kept constant for reliable quantification, because the concentrations of organic solvents affect the ESR signal intensity.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Oxigênio Singlete/análise , Oxirredução , Fármacos Fotossensibilizantes/química , Piperidonas/química , Propionatos/química , Rosa Bengala/química
12.
J Med Chem ; 63(5): 1996-2012, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32039596

RESUMO

Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment option for cancers and other diseases. The key factor that determines the effectiveness of PDT is the photosensitizers (PSs). Upon light irradiation, the PSs would be activated, produce reactive oxygen species (ROS), and induce cell death. One of the challenges is that traditional PSs adopt a large flat disc-like structure, which tend to interact with the adjacent molecules through strong π-π stacking that reduces their ROS generation ability. Aggregation-induced emission (AIE) molecules with a twisted configuration to suppress strong intermolecular interactions represent a new class of PSs for image-guided PDT. In this Miniperspective, we summarize the recent progress on the design rationale of AIE-PSs and the strategies to achieve desirable theranostic applications in cancers. Subsequently, approaches of combining AIE-PS with other imaging and treatment modalities, challenges, and future directions are addressed.


Assuntos
Desenho de Fármacos , Neoplasias/tratamento farmacológico , Estimulação Luminosa/métodos , Fotoquimioterapia/tendências , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Animais , Humanos , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendências
13.
J Fluoresc ; 30(2): 397-406, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32088851

RESUMO

New porphyrin analogues have been designed and synthesized using pyrrole, various aldehydes and propionic acid. The formation of desired compounds was analyzed by utilizing the spectral analysis such as IR, NMR and Mass spectroscopy. The studies on absorption and fluorescence emission of synthesized porphyrins were used to evaluate photophysical characteristics such as molar excitation coefficient and Stokes shift. The estimated values of fluorescence lifetime and fluorescence quantum yield of synthesized porphyrins were found to be variable due to the presence of change in the electron donating and withdrawing characters. The efficiency of generation of singlet oxygen by each synthesized porphyrin as photosensitizer was measured in terms of singlet oxygen quantum yield through photooxidation of 9,10-dimethylantharacene. The obtained singlet oxygen quantum yield values were found to be higher in case of porphyrins those have more electron withdrawing characters rather than donating characters as compared to reference 5,10,15,20-tetraphenylporphyrin (H2TPP). The singlet oxygen quantum yield values of synthesized porphyrins varied from 0.52 to 0.66. Pleasingly, some of synthesized porphyrins are found to be photostable and competent to discover as PDT agents as compared to reference H2TPP.


Assuntos
Desenho de Fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química , Estrutura Molecular , Fármacos Fotossensibilizantes/química , Porfirinas/química , Espectrometria de Fluorescência
14.
Nat Commun ; 11(1): 446, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974383

RESUMO

Afterglow luminescent probes with high signal-to-background ratio show promise for in vivo imaging; however, such probes that can be selectively delivered into target sites and switch on afterglow luminescence remain limited. We optimize an organic electrochromic material and integrate it into near-infrared (NIR) photosensitizer (silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) and (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) containing nanoparticles, developing an H2S-activatable NIR afterglow probe (F12+-ANP). F12+-ANP displays a fast reaction rate (1563 ± 141 M-1 s-1) and large afterglow turn-on ratio (~122-fold) toward H2S, enabling high-sensitivity and -specificity measurement of H2S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H2S-activatable afterglow probe (F12+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (<3 mm in diameter) and orthotopic liver tumors in mice. Strikingly, F12+-ANP-Gal accurately delineates tumor margins in excised hepatic cancer specimens, which may facilitate intraoperative guidance of hepatic cancer surgery.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Sulfeto de Hidrogênio/análise , Neoplasias Hepáticas/diagnóstico por imagem , Substâncias Luminescentes/química , Imagem Molecular/métodos , Animais , Neoplasias Colorretais/sangue , Cistationina beta-Sintase/análise , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/análise , Cistationina gama-Liase/metabolismo , Células Hep G2 , Humanos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/química , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Substâncias Luminescentes/síntese química , Camundongos Endogâmicos BALB C , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Compostos de Vinila/química , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936003

RESUMO

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.


Assuntos
Fluorenos/química , Indóis/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Transferência de Energia , Fluorenos/síntese química , Indóis/síntese química , Luz , Luminescência , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fótons , Porfirinas/química , Oxigênio Singlete/isolamento & purificação , Análise Espectral
16.
Chem Commun (Camb) ; 56(13): 1956-1959, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31956868

RESUMO

Herein, we report a pH stimulus-disaggregated BODIPY sensitizer (PTS) with low background-toxicity for achieving activated photodynamic/photothermal tumor therapy. Both the photodynamic and photothermal properties of PTS can be activated under acidic conditions, and PTS exhibits excellent antitumor properties, which is revealed by both in vitro and in vivo tests.


Assuntos
Compostos de Boro/química , Fármacos Fotossensibilizantes/química , Animais , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Luz , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Transplante Heterólogo
17.
J Photochem Photobiol B ; 204: 111802, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981990

RESUMO

Suitable properties as well as eco-friendly synthesis of photoluminescent Au nanoclusters (NCs) make them promising compounds for biomedical diagnostics and visualization applications. However, the potential photochemical activity of such agents on cancerous cells is largely unknown. The nanoclusters (BSA-Au NCs) were synthetized in the presence of BSA (an average hydrodynamic diameter was about 9.4 nm, while the size of the metal cluster was <1.3 nm according to atomic force microscopy measurements) and possessed a broad photoluminescence band at 680 nm in buffered (pH 7.2) aqueous medium. The photochemical activity was studied by adding two fluorescent probes (dihydrorhodamine or Singlet Oxygen Sensor Green) for detection of reactive oxygen species in samples irradiated at 405 nm to minimize direct excitation of the probes. The photoluminescence measurements evidenced the capability of BSA-Au NCs to generate reactive oxygen species upon light exposure, while the observed sensitivity of the photoluminescence properties might be used to indicate photooxidative processes in the medium. The viability test performed on breast cancer cells after incubation with BSA-Au NCs and subsequent irradiation revealed notable difference in induced phototoxicity between two cell lines, which was not the case after the corresponding treatment using the photosensitizer chlorin e6.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Oxigênio Singlete/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Corantes Fluorescentes/química , Humanos , Lasers Semicondutores , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Oxigênio Singlete/química , Espectrometria de Fluorescência
18.
Chemistry ; 26(8): 1697, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31922634

RESUMO

Invited for the cover of this issue is the group of Torres at the University of Madrid. The image of the cover of this issue depicts cancer cells being destroyed by reactive singlet oxygen produced by ruthenium phthalocyanine glycoconjugates under red light. The work, developed at the Universities of Madrid, Aveiro, Lisbon and Coimbra, describes ruthenium phthalocyanines as powerful bladder cancer PDT agents. Read the full text of the article at 10.1002/chem.201903546.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Humanos , Compostos Organometálicos/síntese química , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico
19.
J Photochem Photobiol B ; 203: 111763, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931382

RESUMO

Photodynamic therapy (PDT) is a clinical modality that allows the destruction of tumor cells and microorganisms by reactive oxygen species, formed by the combination of photosensitizer (PS), molecular oxygen and adequate wavelength light. This research, through a clean methodology that involves pressurized liquids extraction (PLE), obtained a highly antimicrobial extract of Tetragonia tetragonoides, which rich in chlorophylls as photosensitizers. The Chlorophylls-based extract (Cbe-PLE) presented pharmacological safety, through the maintenance of cellular viability. In addition, Cbe-PLE showed great efficacy against Staphylococcus aureus, with severe dose-dependent damage to the cell wall of the pathogen. The obtained product has a high potential for the development of photostimulated phytotherapic formulations for clinical applications in localized infections, as a complementary therapeutic alternative to antibiotics.


Assuntos
Aizoaceae/química , Extratos Vegetais/química , Aizoaceae/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/farmacologia , Luz , Camundongos , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Staphylococcus aureus/efeitos dos fármacos
20.
J Photochem Photobiol B ; 203: 111777, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931387

RESUMO

Despite the high in vitro efficacy of photodynamic therapeutics, lack of tumor targeting significantly reduces their in vivo efficacy and thus limits their clinical use. Photoimmunotherapy (PIT) is a new synthetic strategy to target and treat cancer by photodynamic therapy (PDT). In this study, we describe design and synthesis of a third-generation photosensitizer comprising a PEGylated-phthalocyanine star-polymer photosensitizer that covalently bound to a myeloma tumor-selective antibody (MAb) via the carbodiimide chemistry. The free photosensitizer demonstrated a minimum dark toxicity when tested in mammalian myeloma cell line (SP2/OR); and a moderate phototoxicity after irradiation with non thermal laser red light as a result of light-induced production of cytotoxic singlet oxygen species. Covalent attachment of the photosensitizer (Pc) to the MAb resulted in a significantly enhanced phototoxicity. This is mainly ascribed to the fact that internalization enhances phototoxicity of Pc-MAb bioconjugates. The radioactivated photoimmuno-conjugates 131I(PcMAb) demonstrated the highest phototoxicity to myeloma cells. The suggested bioconjugates are promising candidates as multiple therapeutic models for in vivo treatment of myeloma.


Assuntos
Anticorpos Monoclonais/química , Indóis/química , Fármacos Fotossensibilizantes/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Imunoterapia , Indóis/farmacologia , Radioisótopos do Iodo/química , Marcação por Isótopo , Luz , Camundongos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Oxigênio Singlete/metabolismo
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