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1.
J Phys Chem A ; 123(40): 8644-8649, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31536343

RESUMO

Most of the current efforts in drug discovery are devoted to the design of molecules able to mitigate side effects by concentrating the biological action in the targeted tissue. One promising strategy is photodynamic therapy, which is based on the in situ generation of reactive singlet oxygen upon radiation exposure. However, such an approach requires the use of an efficient photosensitizer. This contribution deals with the optical properties of an Ir(III) complex, [Ir(pbz)2(N^N)] (pbz = 2-phenylbenzimidazole; N^N = methyl 1-butyl-2-pyridyl-benzimidazole-5-carboxylate), which has recently been shown to exhort a strong photoactivity, but still needs further improvements to reach clinical applications. We performed density functional theory calculations at the M06, PBE0, ωB97xD, and CAM-B3LYP levels to predict the impact of introducing electron donor-acceptor groups into the nature of the lowest excited states. The simulations performed demonstrate that the presence of a NH2 at the pbz ligand and a NO2 group at the N^N ligand yield a bathochromic shift of absorption spectrum. We report the most sensitive positions to tune the optical signatures of this family of complexes.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Irídio/química , Antineoplásicos/efeitos da radiação , Complexos de Coordenação/efeitos da radiação , Teoria da Densidade Funcional , Ligantes , Luz , Modelos Químicos , Estrutura Molecular , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação
2.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
3.
Anticancer Res ; 39(8): 4199-4206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366506

RESUMO

BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion. MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC50 was calculated as well as its accumulation in cancer cells was examined by flow cytometry. Confocal microscopy was used to observe the intracellular localization of AcN003HP. The excretion and antitumor effects of AcN003HP were also evaluated in vivo. RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects. CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.


Assuntos
Neoplasias Gastrointestinais/terapia , Glucose/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Citometria de Fluxo , Neoplasias Gastrointestinais/patologia , Glucose/síntese química , Glucose/química , Humanos , Camundongos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/administração & dosagem , Porfirinas/síntese química , Porfirinas/química , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Chem Commun (Camb) ; 55(72): 10792-10795, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31432816

RESUMO

Hypoxia, as an important feature in tumor sites, greatly hinders the performance of photosensitizers, thus affecting the efficacy of photodynamic therapy (PDT). Therefore, designing and preparing new photosensitizer with high photosensitivity under hypoxic condition presents a great challenge that urgently needs to be solved. In this work, a new nano-MOF material using Mn(ii) as the active center can catalytically decompose high concentrations of H2O2 in tumor cells to generate O2, thereby improving the PDT efficacy in hypoxic tumors. The Mn-MOF also produces 1O2 under light irradiation, which finally induces cancer cell apoptosis. This work offers a new strategy for the design and discovery of effective photosensitizers for PDT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Manganês/farmacologia , Estruturas Metalorgânicas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/metabolismo , Manganês/química , Estruturas Metalorgânicas/química , Camundongos , Oxigênio/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
5.
J Chem Theory Comput ; 15(9): 5046-5057, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31390517

RESUMO

Halogenated BODIPY derivatives are emerging as important candidates for photodynamic therapy of cancer cells due to their high triplet quantum yield. We probed fundamental photophysical properties and interactions with biological environments of such photosensitizers. To this end, we employed static TD-DFT quantum chemical calculations as well as TD-DFT surface hopping molecular dynamics on potential energy surfaces resulting from the eigenstates of the total electronic Hamiltonian including the spin-orbit (SO) coupling. Matrix elements of an effective one-electron spin-orbit Hamiltonian between singlet and triplet configuration interaction singles (CIS) auxiliary wave functions are calculated using a new code capable of dealing with singlets and both restricted and unrestricted triplets built up from up to three different and independent sets of (singlet, alpha, and beta) molecular orbitals. The interaction with a biological environment was addressed by using classical molecular dynamics (MD) in a scheme that implicitly accounts for electronically excited states. For the surface hopping trajectories, an accelerated MD approach was used, in which the SO couplings are scaled up, to make the calculations computationally feasible, and the lifetimes are extrapolated back to unscaled SO couplings. The lifetime of the first excited singlet state estimated by semiclassical surface hopping simulations is 139 ± 75 ps. Classical MD demonstrates that halogenated BODIPY in the ground state, in contrast to the unsubstituted one, is stable in the headgroup region of minimalistic cell membrane models, and while in the triplet state, the molecule relocates to the membrane interior ready for further steps of photodynamic therapy.


Assuntos
Compostos de Boro/química , Simulação de Dinâmica Molecular , Fotoquimioterapia , Teoria da Densidade Funcional , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Teoria Quântica , Propriedades de Superfície
6.
Inorg Chem ; 58(16): 10778-10790, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386351

RESUMO

A new family of cyclometalated ruthenium(II) complexes [Ru(N^N)2(C^N)]+ derived from the π-extended benzo[h]imidazo[4,5-f]quinolone ligand appended with thienyl groups (n = 1-4, compounds 1-4) was prepared and its members were characterized for their chemical, photophysical, and photobiological properties. The lipophilicities of 1-4, determined as octanol-water partition coefficients (log Po/w), were positive and increased with the number of thienyl units. The absorption and emission bands of the C^N compounds were red-shifted by up to 200 nm relative to the analogous Ru(II) diimine systems. All of the complexes exhibited dual emission with the intraligand fluorescence (1IL, C^N-based) shifting to lower energies with increasing n and the metal-to-ligand charge transfer phosphorescence (3MLCT, N^N-based) remaining unchanged. Compounds 1-3 exhibited excited state absorption (ESA) profiles consistent with lowest-lying 3MLCT states when probed by nanosecond transient absorption (TA) spectroscopy with 532 nm excitation and had contributions from 1IL(C^N) states with 355 nm excitation. These assignments were supported by the lifetimes observed (<10 ns for the 1IL states and around 20 ns for the 3MLCT states) as well as a noticeable ESA for 3 with 355 nm excitation that did not occur with 532 nm excitation. Compound 4 was the only member of the family with two 3MLCT emissive lifetimes (15, 110 ns), and the TA spectra collected with both 355 and 532 nm excitation was assigned to the 3IL state, which was corroborated by its 4-6 µs lifetime. The ESA for 4 had a rise time of approximately 10 ns and an initial decay of 110 ns, which suggests a possible 3MLCT-3IL excited state equilibrium that results in delayed emission from the 3MLCT state. Compound 4 was nontoxic toward human skin melanoma cells (SKMEL28) in the dark (EC50 = >300 µM); 1-3 were cytotoxic and yielded EC50 values between 1 and 20 µM. The photocytotoxicites with visible light ranged from 87 nM with a phototherapeutic index (PI) of 13 for 1 to approximately 1 µM (PI = >267) for 4. With red light, EC50 values varied from 270 nM (PI = 21) for 3 to 12 µM for 4 (PI = >25). The larger PIs for 4, especially with visible light, were attributed to the much lower dark cytotoxicity for this compound. Because the dark cytotoxicity contributes substantially to the observed photocytotoxicity for 1-3, it was not possible to assess whether the 3IL state of 4 led to a much more potent phototoxic mechanism in the absence of dark toxicity. There was no stark contrast in cellular uptake and accumulation by laser scanning confocal and differential interference contrast microscopy to explain the large differences in dark toxicities between 1-3 and 4. Nevertheless, the study highlights a new family of Ru(II) C^N complexes where π-conjugation beyond a certain point results in low dark cytotoxicity with high photocytotoxicity, opposing the notion that cyclometalated Ru(II) systems are too toxic to be phototherapeutic agents.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Quinolonas/farmacologia , Rutênio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Luz , Estrutura Molecular , Processos Fotoquímicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinolonas/química , Rutênio/química
8.
Life Sci ; 233: 116710, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369762

RESUMO

AIMS: The naturally occurring compound curcumin has been proposed for a number of pharmacological applications. In spite of the promising chemotherapeutic properties of the molecule, the use of curcumin has been largely limited by its chemical instability in water. In this work, we propose the use of water soluble proteins to overcome this issue in perspective applications to photodynamic therapy of tumors. MATERIALS AND METHODS: Curcumin was bound to bovine serum albumin and its photophysical properties was studied as well as its effect on cell viability after light exposure through MTT assay and confocal imaging. KEY FINDINGS: Bovine serum albumin binds curcumin with moderate affinity and solubilizes the hydrophobic compound preserving its photophysical properties for several hours. Cell viability assays demonstrate that when bound to serum albumin, curcumin is an effective photosensitizer for HeLa cells, with better performance than curcumin alone. Confocal fluorescence imaging reveals that when curcumin is delivered alone, it preferentially associates with mitochondria, whereas curcumin bound to bovine serum albumin is found in additional locations within the cell, a fact that may be related to the higher phototoxicity observed in this case. SIGNIFICANCE: The higher bioavailability of the photosensitizing compound curcumin when bound to serum albumin may be exploited to increase the efficiency of the drug in photodynamic therapy of tumors.


Assuntos
Apoproteínas/metabolismo , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Mioglobina/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Soroalbumina Bovina/metabolismo , Animais , Apoproteínas/química , Apoptose/efeitos da radiação , Bovinos , Sobrevivência Celular , Curcumina/química , Células HeLa , Cavalos , Humanos , Mioglobina/química , Fármacos Fotossensibilizantes/química , Soroalbumina Bovina/química
9.
Chem Commun (Camb) ; 55(73): 10972-10975, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31453611

RESUMO

Platinum-resistant cancer cells are sensitive to changes in the levels of reactive oxidative species (ROS). Herein, we design a biotin-modified Ru(ii) complex as a photosensitizer (denoted as Ru-Biotin). Ru-Biotin can selectively target cancer cells and produce vast amounts of singlet oxygen under two-photon excitation at 820 nm leading to cell apoptosis. Ru-Biotin is therefore an excellent candidate to overcome platinum resistance via two-photon photodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Biotina/análogos & derivados , Biotina/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Biotina/síntese química , Biotina/efeitos da radiação , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Humanos , Raios Infravermelhos , Fotoquimioterapia/métodos , Fótons , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo
10.
J Photochem Photobiol B ; 197: 111548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31288120

RESUMO

The visible light combined with photosensitizers (PSs) is exploited in both antitumoral and antimicrobial fields inducing a photo-oxidative stress within the target cells. Among the different PSs, porphyrins belong to the family of the most promising compounds to be used in clinical photodynamic applications. Although in the last years many porphyrins have been synthesised and tested, only a few reports concern the in vitro effects of the 5,15-diarylporphyrins. In this work, the activity of four 5,15-diarylporphyrins (compounds 7-10), bearing alkoxy-linked pyridinium appendixes, have been tested on cancer cell lines and against bacterial cultures. Among the synthetized PSs, compounds 7 and 9 are not symmetrically substituted porphyrins showing one cationic charge tethered at the end of one 4C or 8C carbon chains, respectively. On the other hand, compounds 8 and 10 are symmetrically substituted and show two chains of C4 and C8 carbons featuring a cationic charge at the end of both chains. The dicationic 8 and 10 were more hydrophilic than monocationic 7 and 9, outlining that the presence of two pyridinium salts have a higher impact on the solubility in the aqueous phase than the lipophilic effect exerted by the length of the alkyl chains. Furthermore, these four PSs showed a similar rate of photobleaching, irrespective of the length and number of chains and the number of positive charges. Among the eukaryotic cell lines, the SKOV3 cells were particularly sensitive to the photodynamic activity of all the tested diarylporphyrins, while the HCT116 cells were found more sensitive to PSs bearing C4 chain (7 and 8), regardless the number of cationic charges. The photo-induced killing effect of these porphyrins was also tested against two different bacterial cultures. As expected, the Gram positive Bacillus subtilis was more sensitive than the Gram negative Escherichia coli, and the dicationic porphyrin 8, bearing two C4 chains, was the most efficient on both microorganisms. In conclusion, the new compound 8 seems to be an optimal candidate to deepen as versatile anticancer and antibacterial photosensitizer.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cátions/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/síntese química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo
11.
J Photochem Photobiol B ; 197: 111544, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295716

RESUMO

Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The poor penetration of 5-aminolevulinic acid (5-ALA) with topical application is limited and restrains the production of PpIX which could restrict PDT outcomes. This review will focus on techniques already used to enhance drug penetration in human skin, and will present their results, advantages, and drawbacks. Chemical and physical pretreatments will be discussed. Chemical pre-treatments comprise of drug formulation modification, use of agents that modify the heme cycle, enhance PpIX formation, and the combination of differentiation-promoting agent prior to PDT. On the other hand, physical pretreatments affect the skin barrier by creating holes in the skin or by removing stratum corneum. To promote drug penetration, iontophoresis and temperature modulation are interesting alternative methods. Cellular mechanisms enrolled during chemical or physical pretreatments have been investigated in order to understand how 5-ALA penetrates the skin, why it is preferentially metabolized in PpIX in tumour cells, and how it could be accumulated in deeper skin layers. The objective of this review is to compare clinical trials that use innovative technology to conventional PDT treatment. Most of these pretreatments present good or even better clinical outcomes than usual PDT.


Assuntos
Fármacos Fotossensibilizantes/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/química , Ácido Aminolevulínico/metabolismo , Ácido Aminolevulínico/uso terapêutico , Composição de Medicamentos , Humanos , Lipossomos/química , Micelas , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/metabolismo , Protoporfirinas/uso terapêutico , Neoplasias Cutâneas/patologia
12.
Biomater Sci ; 7(9): 3855-3865, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31305807

RESUMO

Fluorogens with aggregation-induced emission (AIE) characteristics (AIEgens) possess unique optical properties, design flexibility, and multi-functional capabilities and have established their niche as smart materials since their discovery in 2001. In recent years, AIEgens have found varied applications in sensing, imaging, and therapy in biomedical research. In this work, we systematically and comprehensively investigate the in vitro anticancer activity of AIEgens. We report the high cytotoxicity of AIEgens against cancer cells, especially against cancer stem cells (CSCs) which show high resistance to existing therapeutic drug regimens. Furthermore, we explore the role of AIEgens as novel image-guided chemotherapy agents that offer a new avenue for efficient cancer treatment.


Assuntos
Antineoplásicos/química , Corantes Fluorescentes/química , Fármacos Fotossensibilizantes/química , Estilbenos/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Hemólise , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Imagem Óptica/métodos , Fotoquimioterapia , Estilbenos/farmacologia , Nanomedicina Teranóstica
13.
Photochem Photobiol Sci ; 18(8): 2003-2011, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268087

RESUMO

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.69 ± 0.02. In cell cultures, and upon thiol adduct formation, BromoAcroB induced light-dependent cell death in MRC-5 and HeLa cell lines. Using fluorescence microscopy and upon measuring the low yet non-negligible emission of the activated compound, we show that the phototoxicity of the dormant photosensitizer correlated with the quantity of BromoAcroB adducts generated. BromoAcroB thus serves as a dormant photosensitizer sensitive to intracellular electrophile response. Our results highlight the effective control of a triplet state process by modulation of an unsaturated moiety on the BODIPY scaffold and underscore the mechanistic opportunities arising for controlled singlet oxygen production in cells specifically sensitive to electrophile stress.


Assuntos
Acroleína/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Cisteína/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/farmacologia , Acroleína/química , Compostos de Boro/química , Morte Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cisteína/química , Células HeLa , Humanos , Luz , Microscopia de Fluorescência , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Teoria Quântica , Oxigênio Singlete/química
14.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
15.
AAPS PharmSciTech ; 20(7): 253, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31309346

RESUMO

Drug delivery systems (DDS) can be designed to enrich the pharmacological and therapeutic properties of several drugs. Many of the initial obstacles that impeded the clinical applications of conventional DDS have been overcome with nanotechnology-based DDS, especially those formed by chitosan (CS). CS is a linear polysaccharide obtained by the deacetylation of chitin, which has potential properties such as biocompatibility, hydrophilicity, biodegradability, non-toxicity, high bioavailability, simplicity of modification, aqueous solubility, and excellent chemical resistance. Furthermore, CS can prepare several DDS as films, gels, nanoparticles, and microparticles to improve delivery of drugs, such as photosensitizers (PS). Thus, CS-based DDS are broadly investigated for photodynamic therapy (PDT) of cancer and fungal and bacterial diseases. In PDT, a PS is activated by light of a specific wavelength, which provokes selective damage to the target tissue and its surrounding vasculature, but most PS have low water solubility and cutaneous photosensitivity impairing the clinical use of PDT. Based on this, the application of nanotechnology using chitosan-based DDS in PDT may offer great possibilities in the treatment of diseases. Therefore, this review presents numerous applications of chitosan-based DDS in order to improve the PDT for cancer and fungal and bacterial diseases.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Humanos , Micoses/tratamento farmacológico , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Polissacarídeos
17.
Adv Mater ; 31(33): e1901965, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237375

RESUMO

Antibacterial photocatalytic therapy has been reported as a promising alternative water disinfection technology for combating antibiotic-resistant bacteria. Numerous inorganic nanosystems have been developed as antibiotic replacements for bacterial infection treatment, but these are limited due to the toxicity risk of heavy metal species. Organic semiconductor photocatalytic materials have attracted great attention due to their good biocompatibility, chemically tunable electronic structure, diverse structural flexibility, suitable band gap, low cost, and the abundance of the resources they require. An all-organic composite photocatalytic nanomaterial C3 N4 /perylene-3,4,9,10-tetracarboxylic diimide (PDINH) heterostructure is created through recrystallization of PDINH on the surface of C3 N4 in situ, resulting in enhanced photocatalytic efficiency due to the formation of a basal heterostructure. The absorption spectrum of this composite structure can be extended from ultraviolet to near-infrared light (750 nm), enhancing the photocatalytic effect to produce more reactive oxygen species, which have an excellent inactivation effect on both Gram-negative and positive bacteria, while demonstrating negligible toxicity to normal tissue cells. An efficient promotion of infectious wound regeneration in mice with Staphylococcus aureus infected dermal wounds is demonstrated. This all-organic heterostructure shows great promise for use in wound disinfection.


Assuntos
Antibacterianos/química , Imidas/química , Nitrilos/química , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Semicondutores , Animais , Antibacterianos/uso terapêutico , Antibacterianos/toxicidade , Catálise , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Feminino , Luz , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanoestruturas/química , Nitrilos/uso terapêutico , Nitrilos/toxicidade , Perileno/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
18.
J Photochem Photobiol B ; 197: 111533, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254952

RESUMO

Melanoma is one of the most lethal tumors among the skin cancers, arising from complex genetic mutations in melanocyte. Melanoma microenvironment is very heterogeneous, showing complex vascular networks and immunogenicity, as well as induced acquired resistance to treatments by upregulation of multidrug resistance (MDR) mechanisms. Different studies have showed that Photodynamic Therapy (PDT) could be considered a new potential approach for melanoma treatment. PDT combines a light with a specific wavelength and a photosensitizer: when these two elements interact reactive oxygen species (ROS) are generated leading to tumor cell destruction. In this study verteporfin (Ver), a second-generation photosensitizer, has been conjugated with mesoporous silica nanoparticles (MSNs): the resulting Ver-MSNs are an efficient nanoplatforms used to enhance cargo capacity and cellular uptake. Our in vitro and in vivo studies investigated whether Ver-MSNs were able to reduce or inhibit melanoma growth. In vitro experiments performed using B16F10 mouse melanoma cells showed that Ver-MSNs stimulated by red light (693 nm) significantly decreased in vitro cells proliferation in a range of concentration between 0.1 µg/ml to 10 µg/ml. When Ver-MSNs (5 µg/ml in glycerol) were topically administrated to melanoma tumor mass developed in mice and stimulated by red light for four times in 16 days, they were able to reduce the tumor mass of 50.2 ±â€¯6,6% compared to the untreated (only glycerol) mice. In the light of this information, PDT performed using Ver-MSNs could be considered a new promising and potential approach to treat melanoma.


Assuntos
Melanoma Experimental/tratamento farmacológico , Nanopartículas Metálicas/química , Dióxido de Silício/química , Verteporfina/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Feminino , Luz , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Verteporfina/uso terapêutico
19.
Photochem Photobiol Sci ; 18(8): 1923-1932, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31147667

RESUMO

Drug-resistant pathogens, particularly those that result in hospital acquired infections (HAIs), have emerged as a critical priority for the World Health Organization. To address the need for self-disinfecting materials to counter the threat posed by the transmission of these pathogens from surfaces to new hosts, here we investigated if a cationic BODIPY photosensitizer, embedded via electrospinning into nylon and polyacrylonitrile (PAN) nanofibers, was capable of inactivating both bacteria and viruses via antimicrobial photodynamic inactivation (aPDI). Materials characterization, including fiber morphology and the degree of photosensitizer loading, was assessed by scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and UV-visible diffuse reflectance spectroscopy (UV-Vis DRS), and demonstrated that the materials were comprised of nanofibers (125-215 nm avg. diameter) that were thermostable to >300 °C. The antimicrobial potencies of the resultant Nylon-BODIPY(+) and PAN-BODIPY(+) nanofiber materials were evaluated against four strains of bacteria recognized by the World Health Organization as either critical or high priority pathogens: Gram-positive strains methicillin-resistant S. aureus (MRSA; ATCC BAA-44) and vancomycin-resistant E. faecium (VRE; ATCC BAA-2320), and Gram-negative strains multidrug-resistant A. baumannii (MDRAB; ATCC BAA-1605) and NDM-1 positive K. pneumoniae (KP; ATCC BAA-2146). Our results demonstrated the detection limit (99.9999%; 6 log units reduction in CFU mL-1) photodynamic inactivation of three strains upon illumination (30-60 min; 40-65 ± 5 mW cm-2; 400-700 nm): MRSA, VRE, and MDRAB, but only minimal inactivation (47-75%) of KP. Antiviral studies employing PAN-BODIPY(+) against vesicular stomatitis virus (VSV), a model enveloped virus, revealed complete inactivation. Taken together, the results demonstrate the potential for electrospun BODIPY(+)-embedded nanofiber materials as the basis for pathogen-specific anti-infective materials, even at low photosensitizer loadings.


Assuntos
Resinas Acrílicas/farmacologia , Antibacterianos/farmacologia , Compostos de Boro/farmacologia , Nylons/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Resinas Acrílicas/química , Antibacterianos/química , Compostos de Boro/química , Klebsiella pneumoniae/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanofibras/química , Nylons/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Enterococos Resistentes à Vancomicina/efeitos dos fármacos
20.
Anal Bioanal Chem ; 411(20): 5287-5296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201461

RESUMO

Singlet oxygen (1O2) is the focus of study in many fields, including phototoxicity, antioxidant activity, pollutant weathering, photodynamic therapy, and water disinfection. The imidazole plus RNO (Imd/RNO) method, originated by Kraljic and El Mohsni, is commonly used to monitor singlet oxygen production. In this method, 1O2 is quenched by an acceptor, imidazole (Imd), during the formation of a trans-annular peroxide intermediate that bleaches the sensor, p-nitrosodimethylaniline (RNO). Though the method has been widely used, including to monitor 1O2 production in complex environments, such as surfactants and cells, studies reporting the efficiency of the assay in complex solvents have not been reported. In this research, the Imd/RNO method in complex, biorelevant solvents, i.e., sodium dodecyl sulfate, octanol, and phosphate buffer-saturated octanol, was compared with reference solvents, i.e., phosphate buffer, ethanol, and methanol, for monitoring 1O2 produced by Rose Bengal photosensitization using time-resolved, broadband UV-Vis absorbance measurements. Rates of sensor bleaching and sensitizer photodegradation were simultaneously monitored in each solvent to investigate correlations between the disappearance rates of sensor and sensitizer. The quantum yields of 1O2 production (ϕ∆) in each solvent were calculated using a relative actinometric method. The dependence of sensor bleaching and sensitizer degradation on acceptor concentration and solvent polarity, and the results of assay controls suggest mechanistic differences underlying the reactions comprising the Imd/RNO method. These results demonstrate the need for caution and controls when using the method in complex samples including those containing cells, tissues, or nanoscale particles.


Assuntos
Imidazóis/química , Compostos Nitrosos/química , Oxigênio Singlete/análise , Solventes/química , Fármacos Fotossensibilizantes/química , Rosa Bengala/química , Espectrofotometria Ultravioleta
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