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2.
Int J Nanomedicine ; 14: 8285-8302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802866

RESUMO

Background: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. Results: Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Ouro/química , Nanopartículas Metálicas/química , Polímeros/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nanoconjugados/química , Povidona/química , Soro/metabolismo
3.
Int J Nanomedicine ; 14: 8483-8497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695376

RESUMO

Introduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules. Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation. Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%. Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.


Assuntos
Aminas/química , Antibacterianos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Nanopartículas de Magnetita/química , Nanoconjugados/química , Proteínas/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Hemólise/efeitos dos fármacos , Humanos , Nanopartículas de Magnetita/ultraestrutura , Proteínas/química
4.
Chem Commun (Camb) ; 55(93): 14039-14042, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690924

RESUMO

In this work, we have proposed a new strategy to expand the function of a protein. By taking a protease as an example, it can be engineered to make up the shortcoming of natural proteases, and thus it can efficiently and selectively hydrolyze a desired protein even in a complex biological fluid.


Assuntos
Inibidores Enzimáticos/química , Nanoconjugados/química , Peptídeo Hidrolases/química , Aptâmeros de Nucleotídeos/química , DNA/química , Ouro/química , Nanopartículas Metálicas/química , Biologia Molecular/métodos , RNA/química
5.
Mater Sci Eng C Mater Biol Appl ; 104: 109914, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500030

RESUMO

To improve the clinical efficiency of cytotoxic anticancer drugs e.g. doxorubicin (DOX), reduce the severe off-target side effects, and allow the more biocompatible and biodegradable drug penetration into tumor cells, our research efforts developed a new DOX-conjugated protein polymer nanoconjugates (PPNCs) prodrugs delivery system. Briefly, DOX was conjugated to bovine serum albumin (BSA) and the complex was treated with lactobionic acid (LA) as well as folic acid (FA) to enhance drug endocytosis and targeting selectivity. Such functionalized BSA could be conjugated with a designed phenylboronic acid functionalized poly(N-isopropylacrylamide) (PNIPAAm) via forming a pH-sensitive borate ester bond to give the functionalized PPNCs prodrugs. The potential of the PPNCs prodrugs on tumor cells therapy was systematically evaluated in dose/time-dependent effects. In vitro results showed a rapid accumulation of the prodrugs into the MDA-MB-231 tumor cell during the first 30 min and reached maximum at 24 h. Moreover, the cell-killing effect was observed quickly after 4 h incubation with an IC50 of 0.5 mg/mL (≈4 µM/L). In general, given the efficient pH-dependent DOX release of these constructed nanoconjugates, it is anticipated to contribute a potential delivery strategy for cancer therapy.


Assuntos
Boratos/química , Sistemas de Liberação de Medicamentos , Ésteres/química , Nanoconjugados/química , Polímeros/química , Soroalbumina Bovina/química , Animais , Antineoplásicos/farmacologia , Ácidos Borônicos/química , Bovinos , Linhagem Celular Tumoral , Dissacarídeos/química , Doxorrubicina/farmacologia , Ácido Fólico/química , Humanos , Concentração de Íons de Hidrogênio , Pró-Fármacos/farmacologia , Fatores de Tempo
6.
Nat Commun ; 10(1): 3850, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462642

RESUMO

Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood-brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(ß-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Imunoconjugados/administração & dosagem , Nanoconjugados/química , Animais , Antineoplásicos Imunológicos/farmacocinética , Biopolímeros/química , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Glioma/imunologia , Glioma/patologia , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Malatos/química , Camundongos , Permeabilidade , Physarum polycephalum/química , Polímeros/química , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Resultado do Tratamento
7.
Soft Matter ; 15(37): 7420-7428, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31468036

RESUMO

Originally discovered in fundamental research of nanomaterial-biomolecule interactions, protein-nanoparticle co-assembly supraparticles (PNCAS) have become an emerging class of nanomaterials with various biological applications. We apply the interfacial instability process, which was originally reported for forming nanoparticles-encapsulated polymeric micelles, to produce PNCAS. By doing so hydrophobic nanoparticles, which are often the product formed from the upstream nanoparticle synthesis step, can be directly used as the raw materials of the production process of PNCAS. On the other hand, we take advantage of the structural features of protein molecules, in comparison with amphiphilic block copolymers, to mitigate two common problems encountered in the original interfacial instability-mediated nanoparticle encapsulation process, namely (1) poor encapsulation number control and (2) inconvenience and high cost to vary the assembly size. Additionally, we achieve semi-continuous and scalable production of PNCAS by combining the electrospray process and the interfacial instability process. We also conduct proof-of-concept studies of biological applications of the PNCAS products.


Assuntos
Nanopartículas/química , Oligopeptídeos/química , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Nanoconjugados/química , Nanopartículas/metabolismo , Tensoativos/química
8.
Drug Dev Ind Pharm ; 45(9): 1556-1564, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271317

RESUMO

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor. Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR. Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo. Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs. Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Nanoconjugados/química , Compostos Organofosforados/administração & dosagem , Acetais/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Composição de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Micelas , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Compostos Organofosforados/química , Compostos Organofosforados/farmacocinética , Poliésteres/química , Polietilenoglicóis/química , Distribuição Tecidual
9.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261853

RESUMO

Conjugation of latent growth factors to superparamagnetic iron oxide nanoparticles (SPIONs) is potentially useful for magnetically triggered release of bioactive macromolecules. Thus, the goal of this work was to trigger the release of active Transforming Growth-Factor Beta (TGF-ß) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-ß, since heat has been shown to induce release of TGF-ß from the latent complex. Commercially available SPIONS with high specific absorption rates (SAR) were hydrolyzed in 70% ethanol to create surface carboxylic acid conjugation sites for carbodiimide chemistry. Fourier-Transform Infra-Red (FTIR) analysis verified the conversion of maleic anhydride to maleic acid. 1-Ethyl-2-(3-dimethyulaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (Sulfo-NHS) were used to bind to the open conjugation sites of the SPION in order to graft latent TGF-ß onto the particles. The resulting conjugated particles were imaged with transmission electron microscopy (TEM), and the complexed particles were characterized by dynamic light scattering (DLS) and superconducting quantum interference device (SQUID) magnetometry. Enzyme-linked immunosorbent assay (ELISA) was used to assess the thermally triggered release of active TGF-ß from the latent complex, demonstrating that conjugation did not interfere with release. Results showed that latent TGF-ß was successfully conjugated to the iron oxide nanoparticles, and magnetically triggered release of active TGF-ß was achieved.


Assuntos
Carbodi-Imidas/química , Nanopartículas Metálicas/química , Nanoconjugados/química , Fator de Crescimento Transformador beta/química , Liberação Controlada de Fármacos , Compostos Férricos/química , Campos Magnéticos , Succinimidas/química , Fator de Crescimento Transformador beta/administração & dosagem
10.
Biosens Bioelectron ; 141: 111440, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31233987

RESUMO

B-type natriuretic peptide (BNP) is a short peptide that is considered to be an important heart failure (HF)-related biomarker. Due to its low concentration in the blood and short half-life, the sensitive detection of BNP is a bottleneck for diagnosing patients at early stages of HF. In this paper, we report a facile surface plasmon resonance (SPR) sensor to measure BNP; the sensor is based on aptamer-functionalized Au nanoparticles (GNPs-Apt) and antibody-modified magnetoplasmonic nanoparticles (MNPs-Ab) to enable dual screening of BNP in complex environments. During sensing, BNP forms MNP-Ab/BNP/GNP-Apt nanoconjugates that can be rapidly separated from the complex sample by a magnet to avoid degradation within the analyte's half-life. The developed SPR biosensor shows high selectivity, a wide dynamic response range of BNP concentrations from 100 fg/mL to 10 ng/mL, and a low detection limit of 28.2 fg/mL (S/N = 3). Using the proposed sensor, BNP was successfully detected in clinical samples. Thus, the designed SPR biosensor provides a novel and sensitive sensing platform for BNP detection with potential applications in clinical practice.


Assuntos
Aptâmeros de Nucleotídeos/química , Ouro/química , Nanopartículas Metálicas/química , Peptídeo Natriurético Encefálico/sangue , Ressonância de Plasmônio de Superfície/métodos , Anticorpos Imobilizados/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Nanoconjugados/química
11.
Int J Mol Sci ; 20(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31208013

RESUMO

Bacterial infections have caused serious threats to public health due to the antimicrobial resistance in bacteria. Recently, gold nanoclusters (AuNCs) have been extensively investigated for biomedical applications because of their superior structural and optical properties. Great efforts have demonstrated that AuNCs conjugated with various surface ligands are promising antimicrobial agents owing to their high biocompatibility, polyvalent effect, easy modification and photothermal stability. In this review, we have highlighted the recent achievements for the utilizations of AuNCs as the antimicrobial agents. We have classified the antimicrobial AuNCs by their surface ligands including small molecules (< 900 Daltons) and macromolecules (> 900 Daltons). Moreover, the antimicrobial activities and mechanisms of AuNCs have been introduced into two main categories of small molecules and macromolecules, respectively. In accordance with the advancements of antimicrobial AuNCs, we further provided conclusions of current challenges and recommendations of future perspectives of antimicrobial AuNCs for fundamental researches and clinical applications.


Assuntos
Anti-Infecciosos/química , Nanopartículas Metálicas/química , Nanoconjugados/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Ouro/química
12.
Carbohydr Polym ; 220: 30-42, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31196548

RESUMO

Low molecular weight heparin (LMWH) is a natural sulfated glycosaminoglycan with the affinity to proangiogenic factors, rendering it a promising agent for tumor therapy. Inspired by DOX binding to the helix of DNA, mitochondrial damage KLA peptide derivative (mKLA) and anti-angiogenic LMWH-chrysin conjugate (LC) are constructed to simulate the double strands for doxorubicin (DOX) binding (LKD nanocomplex). Initiated and "locked" by DOX, mKLA and LC temporarily aggregate by π-π stacks, electrostatic and hydrophobic interactions in aqueous condition with self-amplified DOX loading (19.07 ± 1.08 wt%). During endosome-lysosome trafficking, DOX protonated by H+ could "unlock" the LKD nanocomplex to disassemble, which enables mKLA and DOX to damage mitochondria and nucleus DNA respectively, and LMWH could also inhibit angiogenesis. Based on the strong inhibition of tumors at all stages in vivo, we hold that LKD nanocomplex provides a new opportunity based on smart construction of carbohydrate materials for clinically advanced cancer patients.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Doxorrubicina/uso terapêutico , Heparina de Baixo Peso Molecular/química , Nanoconjugados/uso terapêutico , Neoplasias/tratamento farmacológico , Peptídeos/uso terapêutico , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , DNA/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Flavonoides/química , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Nanoconjugados/química , Peptídeos/química , Peptídeos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Drug Dev Ind Pharm ; 45(9): 1496-1505, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31241372

RESUMO

Nanomaterial based anticancer treatment is promising nowadays because of their small size that can penetrate and interact both inside and outside the cell surface. In this study, a simple protocol was followed for the conjugation of the biologically synthesized selenium nanoparticles (SeNPs) and short chain synthetic peptide. SeNPs was synthesized by using the culture supernatant of Streptomyces griseoruber, actinomycetes isolated from the soil. The short chain peptide Boc-L-F-OMe was synthesized by the conventional solution phase chemistry using a racemization-free fragment condensation strategy. Peptide interaction with different anticancer receptors was preliminarily studied by docking studies. Biosynthesized SeNPs was conjugated with short chain synthetic peptides by means of cysteine conjugation. Characterization of SeNPs with peptide was done by UV-visible spectroscopy and DLS that showed the red shift in the peak and increase in average particle size and zeta potential, respectively. Bioconjugated SeNPs- peptide was tested for its cytotoxicity against the colon cancer cell line HT-29. Bioconjugated SeNPs-peptide showed enhanced cytotoxic activity when compared to the peptide and nanoparticle alone that was tested at 10-50 µg/ml concentration. Further apoptotic studies were done by AO/PI staining and DNA fragmentation assay that confirms the cytotoxicity of the conjugates. Novel peptide-SeNPs conjugates tested in our study has a significant anticancer activity that can be potentially used for targeting the cancer cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Nanoconjugados/administração & dosagem , Adenocarcinoma/patologia , Antineoplásicos/química , Neoplasias Colorretais/patologia , Dipeptídeos/administração & dosagem , Avaliação Pré-Clínica de Medicamentos , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Nanoconjugados/química , Selênio
14.
Int J Nanomedicine ; 14: 3543-3555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190811

RESUMO

Background: In recent years, non-invasive imaging technologies for early cancer detection have drawn worldwide attention. In this study, an antinucleolin aptamer, AS1411, was successfully conjugated to BODIPY-labeled chitosan and studied on T47D and HEK-293 cell lines. Methods: After conjugation of the aptamer to chitosan nanoparticles and purification, its structure was confirmed using atomic force microscopy (AFM), electrophoretic light scattering (ELS) and dynamic light scattering (DLS). Results of AFM, DLS and ELS of both conjugation and chitosan were compared for confirmation of conjugation. Conjugates were mixed with BODIPY FL fluorescent dye, purified and lyophilized. The labeled conjugate was characterized using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, ELS and DLS. In vitro cellular uptake and cytotoxic effects of BODIPY-labeled chitosan-AS1411 aptamer conjugates were evaluated using the XTT assay on T47D and HEK-293 cells and flow cytometry on T47D cells. Results: The data showed that uptake of BODIPY-labeled chitosan-AS1411 aptamer conjugate was satisfactory. Moreover, there was no statistically significant cytotoxicity of the conjugate on either cell line. Conclusion: The outcomes confirmed the potential application of this new targeted imaging agent as a novel cancer diagnostic agent for molecular imaging.


Assuntos
Compostos de Boro/química , Quitosana/química , Imagem Molecular/métodos , Nanopartículas/química , Oligodesoxirribonucleotídeos/química , Tamanho da Partícula , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Proliferação de Células , Endocitose , Fluorescência , Corantes Fluorescentes/química , Células HEK293 , Humanos , Microscopia de Força Atômica , Nanoconjugados/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
15.
IEEE Trans Nanobioscience ; 18(3): 490-497, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31144642

RESUMO

In this study, we have investigated the structural and optical properties of nanoconjugates (NJs) consisting of phase pure zinc oxide (ZnO) nanoparticles (NPs) with glucose biomolecules. All NJs were fabricated using a standard biochemical synthesis process. Structural, optical, vibrational, and biochemical interface properties of nano-bio composites are probed by different complementary characterization techniques. The XRD patterns of the NPs and NJs illustrate a highly phase pure ZnO structure. A visible green emission in the photoluminescence spectrum, mainly associated with the oxygen vacancies on the surface of ZnO nanostructure, is significantly reduced by the incorporation of glucose biomolecules. The strong binding interaction of glucose biomolecule on the surface of ZnO NPs results in the reduction in green-yellow-orange emission intensities. The interaction of glucose molecules modifies oxygen vacancies by capturing free electrons from the ZnO surface region. Significant changes in the peak intensity and relative peak position of some of the glucose and ZnO NPs in Raman spectra refer to the direct binding between these two nano- and bio-components. In the X-ray photoelectron spectroscopy, the binding energy of O 1s core level in NJs increases from 531 eV (O 1s core level position for ZnO) and the increment is more with higher initial glucose concentration in the solution during synthesis. This study serves as a promising platform for the development of new kinds of NJs and investigation of their interfacial properties which can take the frontier forward for integration and multifunctionality.


Assuntos
Glucose/química , Nanopartículas Metálicas/química , Nanoconjugados/química , Nanotecnologia/métodos , Óxido de Zinco/química , Glucose/metabolismo , Medições Luminescentes , Análise Espectral , Óxido de Zinco/metabolismo
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 219: 450-456, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31063960

RESUMO

In recent, targeting mitochondria in cancer is considered to be a challenging task. This report illustrates preliminary findings from an investigation of the conjugation of gold nanoparticles with a bioactive natural compound, phloroglucinol targeting mitochondrial transmembrane potential of HeLa cancer cells. We systematically investigated the formation of gold-nano conjugates over precisely controlled reaction conditions. Their sharp features enable superior surface plasmon resonance, morphology, surface charge, and stability. We show that gold-nano conjugates scavenging free radicals and persuade cell death in HeLa cancer cells. We also show that gold-nano conjugates induce apoptosis by promoting mitochondrial transmembrane permeation via fluorescent microscopic studies. This work gives new insights into bridging metabolomics and nanotechnology into developing novel lead therapeutic molecules.


Assuntos
Antineoplásicos/administração & dosagem , Ouro/química , Nanopartículas Metálicas/química , Nanoconjugados/química , Floroglucinol/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Floroglucinol/química , Floroglucinol/farmacologia
17.
J Microbiol Biotechnol ; 29(5): 713-720, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31030451

RESUMO

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Anti-Infecciosos/farmacologia , Hipoglicemiantes/farmacologia , Nanoconjugados/química , Amebicidas/química , Anti-Infecciosos/química , Carbamatos/química , Carbamatos/farmacologia , Células HeLa , Humanos , Hipoglicemiantes/química , Nanopartículas Metálicas/química , Piperidinas/química , Piperidinas/farmacologia , Prata/química , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacologia , Vildagliptina/química , Vildagliptina/farmacologia
18.
J Microencapsul ; 36(2): 156-168, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31030591

RESUMO

This study aimed to compare the in vivo effectiveness between curcumin-oligochitosan nanoplexes (CUR-OCH nanoplexes) and oligochitosan-coated curcumin-encapsulated liposomes (OCH-Lip-CUR) with respect to wound healing and scar treatment. Firstly, CUR-OCH nanoplexes was prepared by drug-polysaccharide complexation method and OCH-Lip-CUR was prepared by a combining method of lipid-film hydration and sonication. Their in vitro cytotoxicity and in vivo wound healing and scar treatment effectiveness were evaluated using 3T3 cells and mice Mus musculus var. Albino, respectively. The resutls indicated that both of them were in nanosize with a moderate PDI (less than 0.3), and exhibited negligible cytotoxicity at low CUR concentration (0.01 mg/mL). Moreover, their application onto wounds resulted in faster healing and higher scar treatment effectiveness than control samples. Interestingly, OCH-Lip-CUR exhibited higher in vivo effectiveness than CUR-OCH nanoplexes. However, based on their own advantages, both of them were good candidates for a commercial formulation for wound healing and scar treatment.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cicatriz/tratamento farmacológico , Curcumina/administração & dosagem , Cicatrização/efeitos dos fármacos , Células 3T3 , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Quitina/análogos & derivados , Quitina/química , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Liberação Controlada de Fármacos , Lipossomos/química , Masculino , Camundongos , Nanoconjugados/química
19.
Biomolecules ; 9(4)2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003476

RESUMO

In this study, we identified the proton-coupled folate transporter (PCFT) as a route for targeted delivery of drugs to some gliomas. Using the techniques of confocal imaging, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and small interfering (siRNA) knockdown against the PCFT, we demonstrated that Gl261 and A172 glioma cells, but not U87 and primary cultured astrocytes, express the PCFT, which provides selective internalization of folic acid (FA)-conjugated cytochrome c-containing nanoparticles (FA-Cyt c NPs), followed by cell death. The FA-Cyt c NPs (100 µg/mL), had no cytotoxic effects in astrocytes but caused death in glioma cells, according to their level of expression of PCFT. Whole-cell patch clamp recording revealed FA-induced membrane currents in FA-Cyt c NPs-sensitive gliomas, that were reduced by siRNA PCFT knockdown in a similar manner as by application of FA-Cyt c NPs, indicating that the PCFT is a route for internalization of FA-conjugated NPs in these glioma cells. Analysis of human glioblastoma specimens revealed that at least 25% of glioblastomas express elevated level of either PCFT or folate receptor (FOLR1). We conclude that the PCFT provides a mechanism for targeted delivery of drugs to some gliomas as a starting point for the development of efficient methods for treating gliomas with high expression of PCFT and/or FOLR1.


Assuntos
Neoplasias Encefálicas/metabolismo , Citocromos c/química , Glioma/metabolismo , Nanoconjugados/química , Transportador de Folato Acoplado a Próton/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Citocromos c/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Nanoconjugados/efeitos adversos
20.
ACS Appl Mater Interfaces ; 11(18): 16336-16346, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-30986026

RESUMO

Gold nanoparticles (AuNPs) have emerged as promising drug delivery candidates that can be leveraged for cancer therapy. Lung cancer (LC) is a heterogeneous disease that imposes a significant burden on society, with an unmet need for new therapies. Chemotherapeutic drugs such as afatinib (Afb), which is clinically approved for the treatment of epidermal growth factor receptor positive LC, is hydrophobic and has low bioavailability leading to spread around the body, causing severe side effects. Herein, we present a novel afatinib-AuNP formulation termed Afb-AuNPs, with the aim of improving drug efficacy and biocompatibility. This was achieved by synthesis of an alkyne-bearing Afb derivative and reaction with azide-functionalized lipoic acid using copper-catalyzed click chemistry, then conjugation to AuNPs via alkylthiol-gold bond formation. The Afb-AuNPs were found to possess up to 3.7-fold increased potency when administered to LC cells in vitro and were capable of significantly inhibiting cancer cell proliferation, as assessed by MTT assay and electric cell-substrate impedance sensing, respectively. Furthermore, when exposed to Afb-AuNPs, human alveolar epithelial type I-like cells, a model of the healthy lung epithelium, maintained viability and were found to release less proinflammatory cytokines when compared to free drug, demonstrating the biocompatibility of our formulation. This study provides a new platform for the development of nontraditional AuNP conjugates which can be applied to other molecules of therapeutic or diagnostic utility, with potential to be combined with photothermal therapy in other cancers.


Assuntos
Afatinib/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nanoconjugados/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Afatinib/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Teste de Materiais , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanoconjugados/química , Polietilenoglicóis/química , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/química
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