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1.
Mol Cell Biochem ; 478(7): 1573-1598, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36434145

RESUMO

Today, RNA aptamers are being considered promising theranostic tools against a wide variety of disorders. RNA aptamers can fold into complex shapes and bind to diverse nanostructures, macromolecules, cells, and viruses. It is possible to isolate RNA aptamers from a vast pool of nucleic acids via the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. As therapeutics, aptamers have great potential because of their ability to bind to proteins and selectively limit their activities with negligible side effects. Several RNA aptamers with potential implications in cancer diagnosis are known to confer a great affinity for single-stranded DNA molecules, long non-coding RNAs, circulating tumor cells, vascular endothelial growth factors, and tissue and sera-derived exosomes in patients with different malignancies. Furthermore, clinical investigations have revealed the efficacy of RNA aptamer-based agents in imaging modalities. This review seeks to deliver new insights into the development, classification, nanomerization, and modification of RNA aptamers, as well as their applications in cancer theranostics. The aptamers' mechanism of action and their interest to clinical trials as theranostic agents are also discussed.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Humanos , Aptâmeros de Nucleotídeos/uso terapêutico , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Proteínas
2.
Biomed Pharmacother ; 170: 115973, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064969

RESUMO

The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Humanos , Feminino , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Neoplasias da Mama/tratamento farmacológico , Nanotecnologia , Linhagem Celular Tumoral
3.
Drug Discov Today ; 28(9): 103673, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37331691

RESUMO

Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.


Assuntos
Anti-Infecciosos , Nanoestruturas , Humanos , Cicatrização , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico
4.
J Biomol Struct Dyn ; 40(10): 4682-4696, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33331248

RESUMO

In this study, the Cu(II) complex with Zonisamide (ZNS) and 1, 10-Phenanthroline (Phen) ligands as an anticancer metallodrug was synthesized and characterized successfully by FT-IR, mass spectrometry, TGA, XPS, AAS, CHNSO, magnetic susceptibility and electrical conductivity. The interaction of Cu(II) complex with DNA was explored through a multi-spectroscopic approach such as fluorescence, UV-vis spectrophotometry, CD spectroscopy, and viscosity measurements. Molecular docking simulation was carried out to gain a deeper insight into the target site of DNA which interacted with the mentioned complex. The competitive binding tests with Hoechst 33258 showed that [CuCl2(ZNS)(Phen)EtOH].H2O can bind to the groove site of DNA. The calculated thermodynamic parameters, ΔS° = +201.15 J mol-1K-1 and ΔH° = +41.32 kJ mol-1 confirm that the hydrophobic forces and hydrogen bonding play an essential role in the binding process. The experimental and molecular modeling results demonstrate that the Cu(II) complex binds to DNA through major groove binding. Moreover, the in vitro cytotoxic effects of [CuCl2(ZNS)(Phen)EtOH].H2O against B92 cancer cell lines showed better activity in Cu(II) complex in comparison to free ZNS. Therefore, [CuCl2(ZNS)(Phen)EtOH].H2O can open a new horizon in the treatment of glioma cancer by ZNS metallodrugs.Communicated by Ramaswamy H. Sarma.


Assuntos
Cobre , DNA , Cobre/química , DNA/química , Simulação de Acoplamento Molecular , Fenantrolinas/química , Fenantrolinas/farmacologia , Espectrometria de Fluorescência/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Zonisamida/farmacologia
5.
J Biomol Struct Dyn ; 40(13): 6171-6182, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33525995

RESUMO

In the present study, the interactions between Erythromycin drug and calf thymus deoxyribonucleic acid (ct-DNA) were explored by multi spectroscopic techniques (UV-Visible, fluorescence, circular dichroism spectroscopies), viscosity, molecular docking simulation, and atomic force microscopy (AFM). In addition, the values of binding constant were calculated by the UV-Visible and fluorescence spectroscopy. Competitive fluorescence study with methylene blue (MB), acridine orange (AO), and Hoechst 33258 were indicated that the Erythromycin drug could displace the DNA-bound Hoechst, which displays the strong competition of Erythromycin with Hoechst to interact with the groove binding site of DNA. In addition, the observed complexes in AFM analysis comprise the chains of ct-DNA and Erythromycin with an average size of 314.05 nm. The results of thermodynamic parameter calculations (ΔS° = -332.103 ± 14 J mol-1 K-1 and ΔH° = -115.839 ± 0.02 kJ mol-1) approved the critical role of van der Waals forces and hydrogen bonds in the complexation of Erythromycin-DNA. Fluorescence spectroscopy results demonstrate the existence of a static enhancement mechanism in the interaction of Erythromycin-DNA. According to the obtained results, Erythromycin drug interacts with the major groove of ct-DNA. These consequences were further supported by the molecular docking study, and it could be determined that DNA-Erythromycin docked model was in a rough correlation with our experimental results.Communicated by Ramaswamy H. Sarma.


Assuntos
DNA , Eritromicina , Antibacterianos/farmacologia , Sítios de Ligação , Dicroísmo Circular , DNA/química , Macrolídeos , Simulação de Acoplamento Molecular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica
6.
J Biomol Struct Dyn ; 40(1): 213-225, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873158

RESUMO

In this study, an effective nano-drug delivery system was prepared by the co-precipitation method via two steps; the preparation of Fe3O4 magnetic nanoparticles and its surface modification with layered double hydroxide (LDH) and loading lamivudine on this nanocarrier (Fe3O4@CaAl-LDH@Lamivudine). The developed nanoparticles (NPs) were characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray analysis, Fourier-transformed infrared spectroscopy, vibrating-sample magnetometry, thermogravimetric analysis, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller. The prepared system demonstrated an average size of 130 nm. Also, the drug entrapment efficiency was estimated at ∼70%. In vitro, drug release investigations showed a controlled and pH-dependent lamivudine release over 300 min. The in vitro cytotoxic activity of Fe3O4@CaAl-LDH@Lamivudine NPs was explored against Mel-Rm and A-549 cancer cell lines in comparison with lamivudine and nanocarrier using lactate dehydrogenase colorimetric and MTT assay. The results of the MTT assay revealed that the Fe3O4@CaAl-LDH@Lamivudine NPs significantly inhibited the proliferation of Mel-Rm and A-549 cells in a dose-dependent manner. The influences of Fe3O4@CaAl-LDH@Lamivudine on the cancer cell lines by different therapeutic investigation illustrated the remarkable effect in comparison with free drug. Finally, the achieved consequences confirm the anticancer properties of Fe3O4@CaAl-LDH@Lamivudine and indicate that they may be a cost-effective substitute in the treatment of lung and skin cancer.Communicated by Ramaswamy H. Sarma.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Concentração de Íons de Hidrogênio , Hidróxidos , Lamivudina/farmacologia , Magnetismo , Neoplasias/tratamento farmacológico
7.
Eur J Pharm Biopharm ; 179: 79-94, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36067954

RESUMO

Opioids are generally used as analgesics in pain treatment. Like many drugs, they have side effects when overdosed and can causeaddiction problems.Illegal drug use and misuse are becoming a major concern for authorities worldwide; thus, it is critical to have precise procedures for detecting them in confiscated samples, biological fluids, and wastewaters. Routine blood and urine tests are insufficient for highly selective determinations and can cause cross-reactivities. For this purpose, nanomaterial-based biosensors are great tools to determine opioid intakes, continuously monitoring the drugs with high sensitivity and selectivity even at very low sample volumes.Nanobiosensors generally comprise a signal transducer nanostructure in which a biological recognition molecule is immobilized onto its surface. Lately, nanobiosensors have been extensively utilized for the molecular detection of opioids. The usage of novel nanomaterials in biosensing has impressed researchers who work on developing biosensors. Nanomaterials with a large surface area have been used to develop nanobiosensors with shorter reaction times and higher sensitivity than conventional biosensors. Colorimetric and fluorescence sensing methods are two kinds of optical sensor systems based on nanomaterials. Noble metal nanoparticles (NPs), such as silver and gold, are the most frequently applied nanomaterials in colorimetric techniques, owing to their unique optical feature of surface plasmon resonance. Despite the progress of an extensive spectrum of nanobiosensors over the last two decades, the future purpose of low-cost, high-throughput, multiplexed clinical diagnostic Lab-on-a-Chip instruments has yet to be fulfilled. In this review, a concise overview of opioids (such as tramadol and buprenorphine, oxycodone and fentanyl, methadone and morphine) is provided as well as information on their classification, mechanism of action, routine tests, and new opioid sensing technologies based on various NPs. In order to highlight the trend of nanostructure development in biosensor applications for opioids, recent literature examples with the nanomaterial type, target molecules, and their limits of detection are discussed.


Assuntos
Buprenorfina , Drogas Ilícitas , Tramadol , Analgésicos Opioides/efeitos adversos , Fentanila , Ouro , Metadona , Oxicodona , Prata , Águas Residuárias
8.
J Biomol Struct Dyn ; 39(18): 7160-7167, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-32795166

RESUMO

In this study, the interaction of Fe3O4@CaAl-LDH@L-Dopa nanoparticles (NPs) with human serum albumin (HSA) was investigated in simulated physiological conditions applying UV-visible, fluorescence, and circular dichroism (CD) spectroscopic techniques. The consequences of UV-vis and CD spectroscopy demonstrated that the interaction of HSA to Fe3O4@CaAl-LDH@L-Dopa NPs enforced some conformational alterations within HSA. The fluorescence spectroscopy analysis indicated that by enhancing temperature, the Stern-Volmer quenching constant (Ksv) was decreased, which is relevant to a static quenching mechanism. The binding constant (Kb) was 7.07 × 104M-1 while the number of the binding site (n) was 0.94 which is in compromise with its binding constant. Also, thermodynamic parameters (ΔH° > 0, ΔG° < 0, and ΔS° > 0) have suggested that hydrophobic forces perform a key role in the interaction of HSA with Fe3O4@CaAl-LDH@L-Dopa NPs. Displacement studies successfully carried out using the Warfarin and Ibuprofen have predicted that the binding of Fe3O4@CaAl-LDH@L-Dopa NPs to HSA is situated at site II (subdomain IIIA).Communicated by Ramaswamy H. Sarma.


Assuntos
Levodopa , Albumina Sérica Humana , Sítios de Ligação , Dicroísmo Circular , Humanos , Fenômenos Magnéticos , Simulação de Acoplamento Molecular , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Termodinâmica
9.
Nucleosides Nucleotides Nucleic Acids ; 39(7): 1020-1035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345148

RESUMO

The principal goal of this study is to evaluate the interaction of Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles with calf thymus DNA. The magnetic nanoparticles were previously prepared by a chemical co-precipitation method, and the surface of the Fe3O4 nanoparticles was coated with CaAl layered double hydroxides. The antiparkinsonian drug "L-Dopa" was carried by this core-shell nanostructure to achieve the drug delivery system with suitable properties for biological applications. Also, the interaction of Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles with CT-DNA was studied using, UV-Visible spectroscopy, viscosity, circular dichroism (CD), and fluorescence spectroscopy techniques. The results of investigations demonstrated that Fe3O4@CaAl-LDH@L-Dopa and Fe3O4@CaAl-LDH nanoparticles have interacted via minor groove binding and intercalated to CT-DNA, respectively.


Assuntos
Óxido de Alumínio/química , Cloreto de Cálcio/química , DNA/química , Compostos Férricos/química , Levodopa/química , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Viscosidade
10.
Mater Sci Eng C Mater Biol Appl ; 101: 472-486, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029342

RESUMO

In this study, an efficient drug delivery system composed of Fe3O4, CaAl layered double hydroxide (LDH) and l-Dopa has been synthesized through hydrogen bonds between l-Dopa and CaAl-LDH encapsulated Fe3O4 nanoparticles (Fe3O4@CaAl-LDH@l-Dopa). The structural features of Fe3O4@CaAl-LDH@l-Dopa were characterized using XRD, SEM, TEM, EDX, FT-IR, VSM, TGA, XPS, zeta potential analysis and BET. All of the characterization techniques show the uniform high surface area core-shell structure with about 120 nm in average size. Also, the obtained results clearly indicate that this drug delivery system possess high potent for adsorption of l-Dopa (52 wt%) and high drug encapsulation efficiency (71%). The amount of l-Dopa release in low pHs (53.8%) which simulates the environment of cancer cells is greater than higher pHs. The in vitro cytotoxic and anticancer activities of Fe3O4@CaAl-LDH@l-Dopa were investigated against Mel-Rm Cells Melanoma (NCIt: C3224) using LDH colorimetric assay and differential staining cell death assay. The results showed Fe3O4@CaAl-LDH@l-Dopa with a lower concentration of l-Dopa, illustrate a higher cytotoxicity and anticancer activity.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Hidróxidos/farmacologia , Levodopa/farmacologia , Melanoma/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Concentração de Íons de Hidrogênio , Hidróxidos/química , Levodopa/química
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