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1.
J Biol Inorg Chem ; 29(3): 303-314, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38727821

RESUMEN

This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ∆) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ∆ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.


Asunto(s)
Supervivencia Celular , Indoles , Compuestos de Organosilicio , Neoplasias de la Próstata , Bases de Schiff , Oxígeno Singlete , Humanos , Indoles/química , Indoles/farmacología , Bases de Schiff/química , Bases de Schiff/farmacología , Masculino , Oxígeno Singlete/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Supervivencia Celular/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Células PC-3 , Fotoquimioterapia , Procesos Fotoquímicos , Línea Celular Tumoral , Estructura Molecular
2.
J Nanobiotechnology ; 22(1): 249, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745193

RESUMEN

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Supervivencia Celular , Mitoxantrona , Compuestos de Organosilicio , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Supervivencia Celular/efectos de los fármacos , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Mitoxantrona/farmacología , Mitoxantrona/química , Mitoxantrona/uso terapéutico , Línea Celular Tumoral , Portadores de Fármacos/química , Dióxido de Silicio/química , Porosidad , Liberación de Fármacos , Nanopartículas/química , Células MCF-7 , Nanomedicina/métodos , Especies Reactivas de Oxígeno/metabolismo
3.
Colloids Surf B Biointerfaces ; 238: 113890, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38608462

RESUMEN

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments.


Asunto(s)
Antineoplásicos , Apoptosis , Ferroptosis , Indoles , Mitocondrias , Nanopartículas , Compuestos de Organosilicio , Fotoquimioterapia , Fármacos Fotosensibilizantes , Indoles/química , Indoles/farmacología , Apoptosis/efectos de los fármacos , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Nanopartículas/química , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Propiedades de Superficie
4.
Mikrochim Acta ; 191(3): 153, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393379

RESUMEN

This study introduces aptamer-functionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticles for adenosine triphosphate (ATP) detection where the POSS nanoparticles were synthesized in a one-step, continuous flow microfluidic reactor utilizing thermal polymerization. A microemulsion containing POSS monomers was generated in the microfluidic reactor which was designed to prevent clogging by using a continuous oil flow around the emulsion during thermal polymerization. Surfaces of POSS nanoparticles were biomimetically modified by polydopamine. The aptamer sequence for ATP was successfully attached to POSS nanoparticles. The aptamer-modified POSS nanoparticles were tested for affinity-based biosensor applications using ATP as a model molecule. The nanoparticles were able to capture ATP molecules successfully with an affinity constant of 46.5 [Formula: see text]M. Based on this result, it was shown, for the first time, that microfluidic synthesis of POSS nanoparticles can be utilized in designing aptamer-functionalized nanosystems for biosensor applications. The integration of POSS in biosensing technologies not only exemplifies the versatility and efficacy of these nanoparticles but also marks a significant contribution to the field of biorecognition and sample preparation.


Asunto(s)
Técnicas Biosensibles , Nanopartículas , Compuestos de Organosilicio , Adenosina Trifosfato , Microfluídica , Oligonucleótidos
5.
Mol Omics ; 20(2): 115-127, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-37975521

RESUMEN

Several software packages are available for the analysis of proteomic LC-MS/MS data, including commercial (e.g. Mascot/Progenesis LC-MS) and open access software (e.g. MaxQuant). In this study, Progenesis and MaxQuant were used to analyse the same data set from human liver microsomes (n = 23). Comparison focussed on the total number of peptides and proteins identified by the two packages. For the peptides exclusively identified by each software package, distribution of peptide length, hydrophobicity, molecular weight, isoelectric point and score were compared. Using standard cut-off peptide scores, we found an average of only 65% overlap in detected peptides, with surprisingly little consistency in the characteristics of peptides exclusively detected by each package. Generally, MaxQuant detected more peptides than Progenesis, and the additional peptides were longer and had relatively lower scores. Progenesis-specific peptides tended to be more hydrophilic and basic relative to peptides detected only by MaxQuant. At the protein level, we focussed on drug-metabolising enzymes (DMEs) and transporters, by comparing the number of unique peptides detected by the two packages for these specific proteins of interest, and their abundance. The abundance of DMEs and SLC transporters showed good correlation between the two software tools, but ABC showed less consistency. In conclusion, in order to maximise the use of MS datasets, we recommend processing with more than one software package. Together, Progenesis and MaxQuant provided excellent coverage, with a core of common peptides identified in a very robust way.


Asunto(s)
Imidazoles , Compuestos de Organosilicio , Proteómica , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , Péptidos/química , Proteínas , Hígado/química
6.
Photochem Photobiol ; 100(1): 52-66, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37431229

RESUMEN

To treat a life-threatening disease like cancer, photodynamic therapy (PDT) and sonodynamic therapy (SDT) methods were combined into sono-photodynamic therapy (SPDT) as an effective therapeutic solution. Each day, the usage of phthalocyanine sensitizers increases in the therapeutic applications as they have the ability to produce more reactive oxygen species. In this context, a new diaxially silicon phthalocyanine sensitizer, containing triazole and tert-butyl groups, was synthesized. After elucidating the structure of the complex with elemental analysis, FT-IR, UV-Vis, MALDI-TOF MS and 1 H NMR, its photophysical, photochemical and sono-photochemical properties were examined. When singlet oxygen generation capacity of the new synthesized silicon phthalocyanine complex was determined and compared among photochemical (PDT; Ð¤Δ = 0.59 in DMSO, 0.44 in THF, 0.47 in toluene) and sonophotochemical (SPDT; Ð¤Δ = 0.88 in dimethyl sulfoxide (DMSO), 0.60 in tetrahydrofuran (THF), 0.65 in toluene) methods, it can be said that the complex is a successful sono-photosensitizer that can be used as a good SPDT agent in vitro or in vivo future studies.


Asunto(s)
Indoles , Compuestos de Organosilicio , Fotoquimioterapia , Oxígeno Singlete , Oxígeno Singlete/química , Dimetilsulfóxido , Espectroscopía Infrarroja por Transformada de Fourier , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Tolueno
7.
Bioorg Med Chem Lett ; 97: 129192, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36813052

RESUMEN

To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway.


Asunto(s)
Lesión Renal Aguda , Polisacáridos , Selenio , Animales , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Cisplatino/farmacología , Cisplatino/toxicidad , Riñón/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Selenio/farmacología , Compuestos de Organosilicio/metabolismo , Compuestos de Organosilicio/farmacología
8.
Anal Chim Acta ; 1279: 341785, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37827681

RESUMEN

Extracellular vesicles (EVs) are important participants in numerous pathophysiological processes, and could be used as valuable biomarkers to detect and monitor various diseases. However, facile EV isolation methods are the essential and preliminary issue for their downstream analysis and function investigation. In this work, a polyhedral oligomeric silsesquioxanes (POSS) based hybrid monolith combined metal affinity chromatography (MAC) and distearoyl phospholipid ethanolamine (DSPE) function was developed via photo-initiated thiol-ene polymerization. This synthesis process was facile, simple and convenient, and the obtained hybrid monolith could be applied to efficiently isolate EVs from bio-samples by taking advantages of the specific bond of Ti4+ and phosphate groups on the phospholipid membrane of EVs and the synergistic effect of DSPE insertion. Meanwhile, the eluted EVs could maintain their structural integrity and biological activity, suggesting they could be used for downstream application. Furthermore, 75 up-regulated proteins and 56 down-regulated proteins were identified by comparing the urinary EVs of colorectal cancer (CRC) patients and healthy donors, and these proteins might be used as potential biomarkers for early screening of CRC. These results demonstrated that this hybrid monolith could be used as a simple and convenient tool for isolating EVs from bio-samples and for wider applications in biomarker discovery.


Asunto(s)
Vesículas Extracelulares , Compuestos de Organosilicio , Humanos , Compuestos de Organosilicio/química , Polimerizacion , Interacciones Hidrofóbicas e Hidrofílicas , Biomarcadores , Fosfolípidos
9.
Int J Mol Sci ; 24(12)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37373114

RESUMEN

The biologically active compound 3-aminopropylsilatrane (a compound with a pentacoordinated silicon atom) underwent an aza-Michael reaction with various acrylates and other Michael acceptors. Depending on the molar ratio, the reaction yielded Michael mono- or diadducts (11 examples) containing functional groups (silatranyl, carbonyl, nitrile, amino, etc.). These compounds were characterized via IR and NMR spectroscopy, mass spectrometry, X-ray diffraction, and elemental analysis. Calculations (using in silico, PASS, and SwissADMET online software) revealed that the functionalized (hybrid) silatranes were bioavailable, druglike compounds that exhibited pronounced antineoplastic and macrophage-colony-stimulating activity. The in vitro effect of silatranes on the growth of pathogenic bacteria (Listeria, Staphylococcus, and Yersinia) was studied. It was found that the synthesized compounds exerted inhibitory and stimulating effects in high and low concentrations, respectively.


Asunto(s)
Antineoplásicos , Compuestos de Organosilicio , Antineoplásicos/farmacología , Antineoplásicos/química , Difracción de Rayos X , Espectrometría de Masas , Estructura Molecular
10.
Chem Biodivers ; 20(4): e202201167, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36912724

RESUMEN

In this study, three new axially disubstituted silicon phthalocyanines (SiPc1-3) and their quaternized phthalocyanine derivatives (QSiPc1-3) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds (QSiPc1-3) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1-3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.


Asunto(s)
Antiinfecciosos , Antineoplásicos , Compuestos de Organosilicio , Staphylococcus aureus , Humanos , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral/efectos de los fármacos , ADN/química , Escherichia coli/efectos de los fármacos , Ligandos , Staphylococcus aureus/efectos de los fármacos , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacología
11.
J Colloid Interface Sci ; 630(Pt A): 266-273, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36242886

RESUMEN

As a new kind of drug carrier, practical applications of hollow periodic mesoporous organosilica (HPMO) have been greatly limited by their low loading capacity for hydrophobic drugs. In this work, we demonstrated the preparation of HPMO capsules with tunable shell thickness by using 1,2-bis(triethoxysilyl)ethane as the precursor. The capsules with thin shells and thus low Young's modulus showed excellent swellability to organic solvents containing hydrophobic drugs. As a result, hydrophobic drugs, i.e., paclitaxel (PTX) could be loaded into the hollow interior of the HPMO capsules with 4 nm shell at an efficiency of ca. 120 %. The as-prepared PTX-loaded HPMO capsules were dispersible in aqueous media and showed improved performance in killing cancer cells compared to free PTX.


Asunto(s)
Compuestos de Organosilicio , Compuestos de Organosilicio/química , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Paclitaxel/farmacología , Cápsulas
12.
Anal Chim Acta ; 1225: 340249, 2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36038243

RESUMEN

Nitrofurazone (NFZ) is carcinogenic and mutagenic to human in long-term ingestion, and it is prohibited to be added in food. In this work, a novel triphenylbenzene (TPB) functionalized fluorescent hybrid porous polymers (POSS@TPB) was constructed by using polyhedral oligomeric silsesquioxane (POSS) as the rigid group and TPB as the core unit of high fluorescence. The morphology and physicochemical properties of POSS@TPB were characterized in detail. Moreover, the synergistic effect of inner filter effect and photoinduced electron transfer is verified by experimental and simulation results. After condition optimization, a NFZ analysis method based on POSS@TPB probe was established with a linear range of 0.4-16.5 mg/L and a detection limit of 0.13 mg/L. In addition, the fluorescent probe has good stability, anti-interference and considerable reusability. At the same time, the selective analysis of trace NFZ in aquatic product and cosmetics was carried out with satisfied recoveries of 87%-110.6% and relative standard deviation less than 4.1%. And the results were verified by high-performance liquid chromatography method. Overall, this fluorescence sensor has excellent performance in NFZ analysis, which provides a broad application prospect for the repeatable and selective residue NFZ analysis in aquatic product and cosmetics.


Asunto(s)
Cosméticos , Compuestos de Organosilicio , Cromatografía Líquida de Alta Presión/métodos , Humanos , Nitrofurazona , Compuestos de Organosilicio/química , Polímeros/química , Porosidad
13.
Front Public Health ; 10: 902799, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35801234

RESUMEN

Synthetic amorphous silica (SAS) is industrially relevant material whose bioactivity in vitro is strongly diminished, for example, by protein binding to the particle surface. Here, we investigated the in vitro bioactivity of fourteen SAS (pyrogenic, precipitated, or colloidal), nine of which were surface-treated with organosilanes, using alveolar macrophages as a highly sensitive test system. Dispersion of the hydrophobic SAS required pre-wetting with ethanol and extensive ultrasonic treatment in the presence of 0.05% BSA (Protocol 1). Hydrophilic SAS was suspended by moderate ultrasonic treatment (Protocol 2) and also by Protocol 1. The suspensions were administered to NR8383 alveolar macrophages under serum-free conditions for 16 h, and the release of LDH, GLU, H2O2, and TNFα was measured in cell culture supernatants. While seven surface-treated hydrophobic SAS exhibited virtually no bioactivity, two materials (AEROSIL® R 504 and AEROSIL® R 816) had minimal effects on NR8383 cells. In contrast, non-treated SAS elicited considerable increases in LDH, GLU, and TNFα, while the release of H2O2 was low except for CAB-O-SIL® S17D Fumed Silica. Dispersing hydrophilic SAS with Protocol 1 gradually reduced the bioactivity but did not abolish it. The results show that hydrophobic coating reagents, which bind covalently to the SAS surface, abrogate the bioactivity of SAS even under serum-free in vitro conditions. The results may have implications for the hazard assessment of hydrophobic surface-treated SAS in the lung.


Asunto(s)
Compuestos de Organosilicio , Dióxido de Silicio , Peróxido de Hidrógeno/farmacología , Indicadores y Reactivos , Tamaño de la Partícula , Dióxido de Silicio/química , Factor de Necrosis Tumoral alfa
14.
ACS Appl Bio Mater ; 5(8): 3936-3950, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35802827

RESUMEN

Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.


Asunto(s)
Neoplasias Colorrectales , Inhibidores de la Ciclooxigenasa , Antiinflamatorios no Esteroideos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/farmacología , Células HT29 , Humanos , Indoles , Compuestos de Organosilicio , Silicio/uso terapéutico
15.
Microbiol Spectr ; 10(1): e0146621, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35196798

RESUMEN

Bacterial pathogens are progressively adapting to current antimicrobial therapies with severe consequences for patients and global health care systems. This is critically underscored by the rise of methicillin resistant Staphylococcus aureus (MRSA) and other biofilm-forming staphylococci. Accordingly, alternative strategies have been explored to fight such highly multidrug resistant microorganisms, including antimicrobial photodynamic therapy (aPDT) and phage therapy. aPDT has the great advantage that it does not elicit resistance, while phage therapy allows targeting of specific pathogens. In the present study, we aimed to merge these benefits by conjugating the cell-binding domain (CBD3) of a Staphylococcus aureus phage endolysin to a photoactivatable silicon phthalocyanine (IRDye 700DX) for the development of a Staphylococcus-targeted aPDT approach. We show that, upon red-light activation, the resulting CBD3-700DX conjugate generates reactive oxygen species that effectively kill high loads of planktonic and biofilm-resident staphylococci, including MRSA. Furthermore, CBD3-700DX is readily internalized by mammalian cells, where it allows the targeted killing of intracellular MRSA upon photoactivation. Intriguingly, aPDT with CBD3-700DX also affects mammalian cells with internalized MRSA, but it has no detectable side effects on uninfected cells. Altogether, we conclude that CBD3 represents an attractive targeting agent for Staphylococcus-specific aPDT, irrespective of planktonic, biofilm-embedded, or intracellular states of the bacterium. IMPORTANCE Antimicrobial resistance is among the biggest threats to mankind today. There are two alternative antimicrobial therapies that may help to control multidrug-resistant bacteria. In phage therapy, natural antagonists of bacteria, lytic phages, are harnessed to fight pathogens. In antimicrobial photodynamic therapy (aPDT), a photosensitizer, molecular oxygen, and light are used to produce reactive oxygen species (ROS) that inflict lethal damage on pathogens. Since aPDT destroys multiple essential components in targeted pathogens, aPDT resistance is unlikely. However, the challenge in aPDT is to maximize target specificity and minimize collateral oxidative damage to host cells. We now present an antimicrobial approach that combines the best features of both alternative therapies, namely, the high target specificity of phages and the efficacy of aPDT. This is achieved by conjugating the specific cell-binding domain from a phage protein to a near-infrared photosensitizer. aPDT with the resulting conjugate shows high target specificity toward MRSA with minimal side effects.


Asunto(s)
Antibacterianos/farmacología , Endopeptidasas/farmacología , Fotoquimioterapia , Infecciones Estafilocócicas/microbiología , Fagos de Staphylococcus/química , Staphylococcus/efectos de los fármacos , Staphylococcus/fisiología , Animales , Antibacterianos/química , Biopelículas/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Endopeptidasas/química , Endopeptidasas/metabolismo , Humanos , Indoles/química , Luz , Compuestos de Organosilicio/química , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus/virología , Fagos de Staphylococcus/metabolismo
16.
Mikrochim Acta ; 189(3): 85, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35129695

RESUMEN

For the first time a hybrid molecularly imprinted polymer (MIP) doped with 3-(trimethoxysilyl) propyl methacrylate (γ-MPS)-modified mesoporous molecular sieve SBA-15 for target peptide recognition has been developed. Zinc acrylate and methacrylic acid were used as binary functional monomers, and ethylene dimethacrylate was used as cross-linking agent to prepare an imprinted monolith against Val-Tyr-Ala-Leu-Lys(glutarylation) (VYALKglu). The morphology of the polymers was characterized by scanning electron microscopy, FT-IR spectroscopy, energy dispersive spectroscopy, and 1H NMR. The SBA-15-MPS MIP showed high recovery of 87.1% and the IF of 12.9 for the enrichment of the template peptide. When the template peptide concentration ranged from 5 to 90 µg mL-1, the correlation coefficients (R2) for the calibration function obtained was better 0.999. The limit of detection (LOD, 0.30 µg mL-1) and limit of quantification (LOQ, 1.0 µg mL-1) were achieved for signal-to-noise ratios of 3:1 and 10:1, respectively. When other kinds of synthetic peptides were used as analogs, the selectivity of the SBA-15-MPS MIP was much better than the SBA-15-MPS NIP (without template peptides) with relative selectivity coefficients of 52.8-265. In contrast, little quinolones and biogenic amines are adsorbed with the SBA-15-MPS MIP. The SBA-15-MPS MIP could enrich VYALKglu from spiked histone digestion with the average recovery of 87.8% and the relative standard deviation (RSD) of 0.99%. As a conclusion, doping of SBA-15 is an effective approach to the improvement of performance of molecularly imprinted monolith.


Asunto(s)
Metacrilatos/química , Polímeros Impresos Molecularmente/química , Compuestos de Organosilicio/química , Péptidos/análisis , Dióxido de Silicio/química , Adsorción , Tamaño de la Partícula , Porosidad , Propiedades de Superficie
17.
Photodiagnosis Photodyn Ther ; 37: 102734, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35066132

RESUMEN

BACKGROUND: Photodynamic therapy (PDT) is one of the effective methods that can be used in cancer treatment. In this study, we aimed to investigate the PDT-mediated anti-cancer effects of newly synthesized piperazine-substituted silicon phthalocyanine molecules on breast cancer cells. METHODS: The compounds were analyzed by different spectroscopic techniques (FT-IR, UV-vis, 1H NMR, 13C NMR, MS) and the absorbance characteristics were determined. The cytotoxic effects of silicon phthalocyanines on MDA-MB-231 breast cancer cells and non-tumorigenic MCF-10A cells were evaluated using MTT assay. Detection of apoptotic populations was performed by Annexin V/7AAD assay. H2DCFDA dye was used to analyze intracellular reactive oxygen species. The clonogenic activity and cellular motility were analyzed by colony formation assay and in vitro scratch assay, respectively. Caspase-3, PARP1, and cleaved-PARP1 protein levels were analyzed by western blot studies. RESULTS: Piperazine-substituted silicon phthalocyanines caused high levels of cytotoxic effects and apoptotic cell population in MDA-MB-231 cells, while low levels of cytotoxic effects were observed in MCF-10A cells. Following PDT, intense ROS formation was detected in MDA-MB-231 cells. Colony-forming capacity and cellular motility of MDA-MB-231 cells were highly restricted following PDT, whereas these effects were observed at lower levels in MCF-10A cells. Silicon phthalocyanines caused different effects on cleaved-PARP1 expressions of MDA-MB-231 and MCF-10A cells. CONCLUSION: These results suggest that piperazine-substituted silicon phthalocyanines can exert selective anti-cancer effects on breast cancer cells and activate cellular death through different molecular pathways. Hence, we believe that they may be used as effective photosensitizer agents in the future.


Asunto(s)
Neoplasias de la Mama , Fotoquimioterapia , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Humanos , Indoles , Compuestos de Organosilicio , Fotoquimioterapia/métodos , Piperazina/farmacología , Espectroscopía Infrarroja por Transformada de Fourier
18.
J Hazard Mater ; 421: 126824, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34396973

RESUMEN

Hydrophobic and oleophilic materials are attractive candidates for efficient oil collection due to their excellent oil-water separation. However, the most of currently reported oil adsorption materials are limited resources or require complicated preparation steps, which causes high energy consumption and not be practical for large-scale application. Herein, we report a facile strategy to modify the wettability of Enteromorpha from hydrophilic to hydrophobic, which not only greatly reduces energy consumption but also shows the outstanding capacity for oil-water separation with the maximum adsorption capacities is 11.4 g/g and the contact angle reaches 137°. The successful modification of the Enteromorpha is achieved by grafting n-octyltriethoxysilane on the surface of the pristine Enteromorpha. The hydrophobic and superoleophilic Enteromorpha guarantee adequate voids in the fibrous bundles only for oil adsorption and the oil floating on the seawater is removed by the formation of hydrogen bonding between oil and modified Enteromorpha. By optimizing test, the optimal adsorption conditions are adsorption time of 60 min, oil-water ratio of 1:10 and pH of 7. Our reported hydrophobic organosilane modified Enteromorpha will open a new avenue to control marine oil pollution and suppress the damage of Enteromorpha to the marine ecology system.


Asunto(s)
Compuestos de Organosilicio , Contaminación por Petróleo , Adsorción , Interacciones Hidrofóbicas e Hidrofílicas , Contaminación por Petróleo/análisis , Agua
19.
Sci Total Environ ; 806(Pt 4): 151388, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34740650

RESUMEN

Since microplastics were recognized as a global environmental problem in the early 2000s, research began on possible solutions such as the removal of microplastics from waters. A novel and promising approach for this purpose is microplastics agglomeration-fixation using organosilanes. In this study, it is investigated how biofilm coverage of microplastics affects this process. The biofilm was grown on the microplastics by cultivating it for one week in a packed bed column operated with biologically treated municipal wastewater enriched with glucose. The biofilm was characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and Fourier-Transform infrared spectroscopy (FT-IR). The results show a partial coverage of the microplastics with attached bacteria and extracellular polymeric substances (EPS) after 7 days of incubation. Comparing five polymer types (polyethylene, polypropylene, polyamide, polyester, and polyvinyl chloride) and three organosilanes, the biofilm coverage caused a reduced removal efficiency for all combinations tested as it changes the surface chemistry of the microplastics and therefore the interaction with the organosilanes tested in this study. Treatment of biofilm covered microplastic with ultrasound partly recovers the removal. However, the results underline the importance of simulated environmental exposure when performing experiments for microplastic removal.


Asunto(s)
Compuestos de Organosilicio , Contaminantes Químicos del Agua , Biopelículas , Monitoreo del Ambiente , Microplásticos , Plásticos , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/análisis
20.
Drug Deliv ; 29(1): 161-173, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34967262

RESUMEN

A major impediment in the development of nanoplatform-based ovarian cancer therapy is endo/lysosome entrapment. To solve this dilemma, a hollow mesoporous organosilica-based nanoplatform (HMON@CuS/Gd2O3) with a mild-temperature photothermal therapeutic effect and multimodal imaging abilities was successfully synthesized. HMON@CuS/Gd2O3 exhibited an appropriate size distribution, L-glutathione (GSH)-responsive degradable properties, and high singlet oxygen generation characteristics. In this study, the nanoplatform specifically entered SKOV-3 cells and was entrapped in endo/lysosomes. With a mild near infrared (NIR) power density (.5 W/cm2), the HMON@CuS/Gd2O3 nanoplatform caused lysosome vacuolation, disrupted the lysosomal membrane integrity, and exerted antitumour effects in ovarian cancer. Additionally, our in vivo experiments indicated that HMON@CuS/Gd2O3 has enhanced T1 MR imaging, fluorescence (FL) imaging (wrapping fluorescent agent), and infrared thermal (IRT) imaging capacities. Using FL/MRI/IRT imaging, HMON@CuS/Gd2O3 selectively caused mild phototherapy in the cancer region, efficiently inhibiting the growth of ovarian cancer without systemic toxicity in vivo. Taken together, the results showed that these well-synthesized nanoplatforms are likely promising anticancer agents to treat ovarian cancer and show great potential for biomedical applications.


Asunto(s)
Endosomas/efectos de los fármacos , Compuestos de Organosilicio/química , Neoplasias Ováricas/patología , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Femenino , Humanos , Concentración de Iones de Hidrógeno , Imagen Multimodal , Propiedades de Superficie
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