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1.
Chem Commun (Camb) ; 56(11): 1661-1664, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31939463

RESUMO

We describe a novel class of stimuli-sensitive sulfonium-based synthetic lipids, which exhibit several favorable biophysical properties of phospholipids. The potent sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity against mammalian cells and displayed moderate antibacterial activities.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/farmacologia , Compostos de Sulfônio/farmacologia , Antibacterianos/síntese química , Antibacterianos/toxicidade , Derivados de Benzeno/síntese química , Derivados de Benzeno/farmacologia , Derivados de Benzeno/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Escherichia coli/efeitos dos fármacos , Humanos , Lipídeos/síntese química , Lipídeos/farmacologia , Lipídeos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/toxicidade
2.
Appl Microbiol Biotechnol ; 104(5): 1955-1976, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970432

RESUMO

Aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria. The mechanism of bactericidal action by aminoglycosides is well-known, by which it terminates the cytoplasmic protein synthesis. However, the potentials of aminoglycosides become hindered when facing the evolution of bacterial resistance mechanisms. Among multiple resistance mechanisms displayed by bacteria against antibiotics, the formation of biofilm is the mechanism that provides a barrier for antibiotics to reach the cellular level. Bacteria present in the biofilm also get protection against the impact of host immune responses, harsh environmental conditions, and other antimicrobial treatments. Hence, with the multifaceted resistance developed by biofilm-forming pathogenic bacteria, antibiotics are therefore discontinued for further applications. However, the recent research developed several alternative strategies such as optimization of the active concentration, modification of the environmental conditions, modification of the chemical structure, combinatorial application with other active agents, and formulation with biocompatible carrier materials to revitalize and exploit the new potential of aminoglycosides. The present review article describes the above mentioned multiple approaches and possible mechanisms for the application of aminoglycosides to treat biofilm-associated infections.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Adjuvantes Farmacêuticos/química , Adjuvantes Farmacêuticos/farmacologia , Adjuvantes Farmacêuticos/uso terapêutico , Aminoglicosídeos/química , Aminoglicosídeos/uso terapêutico , Antibacterianos/química , Antibacterianos/uso terapêutico , Bactérias/crescimento & desenvolvimento , Bactérias/patogenicidade , Infecções Bacterianas/tratamento farmacológico , Biofilmes/crescimento & desenvolvimento , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Portadores de Fármacos/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada , Humanos , Fatores de Virulência/metabolismo
3.
BMC Complement Altern Med ; 19(1): 334, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771651

RESUMO

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.


Assuntos
Benzoquinonas , Portadores de Fármacos , Nanomedicina/métodos , Fosfolipídeos , Psoríase , Animais , Benzoquinonas/administração & dosagem , Benzoquinonas/química , Benzoquinonas/farmacocinética , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Camundongos , Nigella sativa/química , Fosfolipídeos/química , Fosfolipídeos/farmacocinética , Fosfolipídeos/farmacologia , Psoríase/metabolismo , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Absorção Cutânea/efeitos dos fármacos
4.
Int J Nanomedicine ; 14: 6799-6812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692522

RESUMO

Background: Photodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers. Purpose: The objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause. Methods: We synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo. Results: Our PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models. Conclusion: Our current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.


Assuntos
Ácido Fólico/farmacologia , Indóis/farmacologia , Nanopartículas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Estabilidade de Medicamentos , Feminino , Ácido Fólico/química , Células HeLa , Humanos , Indóis/química , Células MCF-7 , Camundongos , Nanomedicina , Nanopartículas/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Carbohydr Polym ; 226: 115297, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582090

RESUMO

Aiming to enhance therapeutic efficiency and reduce toxic effect of norcantharidin (NCTD), NCTD-conjugated carboxymethyl chitosan (CMCS) conjugates (CNC) were prepared and evaluated for the treatment of hepatocellular carcinoma. In vitro cellular assays revealed that CNC conjugates possessed potent inhibitory effects on the proliferation and migration of BEL-7402 cells. Besides, CNC could change nuclear morphology of tumor cells. In comparison with free NCTD at equivalent dose, CNC exerted enhanced therapeutic efficiency and diminished systemic toxicity in H22 tumor-bearing mice with a tumor inhibition rate of 56.20%. Further investigation about pharmacokinetics and tissue distribution by high performance liquid chromatography (HPLC) analysis indicated that CNC showed a longer retention time in blood circulation and reduced distribution in heart and kidney tissues, thereby exerting different antitumor efficacy and toxicity compared with free NCTD. Our results suggested that CNC conjugates based on CMCS as polymer carriers might be used as a potential clinical alternative for NCTD in tumor therapy.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quitosana/análogos & derivados , Portadores de Fármacos , Neoplasias Hepáticas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Camundongos
6.
Nat Commun ; 10(1): 4492, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582802

RESUMO

Drug delivery with nanocarriers relies on the interaction of individual nanocarriers with the cell surface. For lipid-based NCs, this interaction uniquely involves a process of membrane fusion between the lipid bilayer that makes up the NC and the cell membrane. Cubosomes have emerged as promising fusogenic NCs, however their individual interactions had not yet been directly observed due to difficulties in achieving adequate resolution or disentangling multiple interactions with common characterization techniques. Moreover, many studies on these interactions have been performed under static conditions which may not mimic the actual transport of NCs. Herein we have observed fusion of lipid cubosome NCs with lipid bilayers under flow. Total internal reflection microscopy has allowed visualisation of the fusion event which was sensitive to the lipid compositions and rationalized by lipid diffusion. The fusion event in supported lipid bilayers has been compared with those in cells, revealing a distinct similarity in kinetics.


Assuntos
Membrana Celular/metabolismo , Portadores de Fármacos/farmacologia , Microscopia Intravital/métodos , Fusão de Membrana , Animais , Linhagem Celular , Membrana Celular/ultraestrutura , Portadores de Fármacos/química , Células Epiteliais , Fibroblastos , Humanos , Bicamadas Lipídicas/metabolismo , Lipídeos/química , Camundongos , Microscopia de Força Atômica , Microscopia de Interferência , Nanopartículas/química , Células-Tronco , Imagem com Lapso de Tempo
7.
Artif Cells Nanomed Biotechnol ; 47(1): 3961-3975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588802

RESUMO

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Emodina/química , Hidrogéis/química , Peptídeos/química , Células A549 , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emodina/administração & dosagem , Emodina/farmacologia , Células Hep G2 , Humanos , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Suspensões
8.
Artif Cells Nanomed Biotechnol ; 47(1): 4053-4058, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31608701

RESUMO

This paper aims to demonstrate the efficacy of the immobilisation of the chemotherapy drug doxorubicin on nanodiamond platforms as a potential cancer therapy. This effective drug is experimentally fed into a human breast adenocarcinoma cell lines. Drug loading activity and cell viability are detected by spectrometer, microscopy, and MTT assay in this study at Biomedical Physics Research Unit, Department of Physics, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand between 1 Oct 2018 and 10 Jun 2019. Experimental results show that in the basic environment (pH = 8.0), the nanodiamond carboxylic group cooperated with the doxorubicin amino group to form a stable and non-covalent bond on nanodiamond surfaces served as a simple physical adsorption. In an acidic environment suitable to targeting the cancer cells, the nanodiamond carboxylic group ionised so that doxorubicin is effectively released. Doxorubicin therefore affirmatively absorbed into the cytoplasm and later into the nucleus. The significant finding of the study is that IC-50 equivalent to 0.40 mg/mL and viable nanodiamond-doxorubicin is a good candidate material for drug delivery.


Assuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanodiamantes/química , Adenocarcinoma/patologia , Adsorção , Animais , Antibióticos Antineoplásicos/metabolismo , Neoplasias da Mama/patologia , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/metabolismo , Doxorrubicina/metabolismo , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Células MCF-7 , Células Vero
9.
Nanoscale ; 11(37): 17357-17367, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31517372

RESUMO

Nanoparticles are routinely used in cell biology. They deliver drugs or function as labels or sensors. For many of these applications it is essential that the nanoparticles enter the cells. While some cell types readily ingest all kinds of particles, others just don't. We report that uptake can be enhanced for some cells if the particles are administered from the basolateral side of the cells (in this case from below). Compared to apical uptake (from above), we report an 8-fold increase in the number of fluorescent nanodiamonds internalized by the colon cancer cell line HT29. Up to 96% of the cells treated by a modified protocol contain at least one nanodiamond, whereas in the control group we could observe nanodiamonds in less than half of the cells. We were also able to show that simple treatment of cell clusters with trypsin-EDTA leads to the same enhancement of the nanodiamond uptake as seeding the cells on top of the nanoparticles. Although our study is focused on nanodiamonds in HT29 cells, we believe that this method could also be applicable for other nanoparticles and cells with a specific directionality.


Assuntos
Neoplasias do Colo/metabolismo , Portadores de Fármacos , Nanodiamantes/química , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ácido Edético/farmacologia , Humanos , Tripsina/farmacologia
10.
Artif Cells Nanomed Biotechnol ; 47(1): 3832-3838, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556316

RESUMO

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, Bi2S3 biocompatible particles coated with bovine serum albumin (BSA) (Bi2S3@BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the Bi2S3@BSA (Bi2S3@BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The Bi2S3@BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of Bi2S3@BSA HNPs. The result of this study proved that Bi2S3@BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, Bi2S3@BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells.


Assuntos
Bismuto/farmacologia , Quimiorradioterapia , Minerais/química , Soroalbumina Bovina/química , Sulfetos/síntese química , Sulfetos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Bismuto/química , Bovinos , Técnicas de Química Sintética , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Química Verde , Células HT29 , Humanos , Nanopartículas/química , Tamanho da Partícula , Radiossensibilizantes/síntese química , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Sulfetos/química
11.
J Microbiol Biotechnol ; 29(11): 1799-1805, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31546295

RESUMO

Doxorubicin (DOX) is one of the most effective anticancer agents used for the treatment of multiple cancers; however, its use is limited by its short half-life and adverse drug reactions, especially cardiotoxicity. In this study, we found that the conjugate of DOX with APTA12 (Gemcitabine incorporated G-quadruplex aptamer) was significantly more cancer selective and cytotoxic than DOX. The conjugate had an affinity for nucleolin, with higher uptake and retention into the cancer cells than those of DOX. Further, it was localized to the nucleus, which is the target site of DOX. Owing to its mechanism of action, DOX has the ability to intercalate into the nucleotides thus making it a suitable drug to form a conjugate with cancer selective aptamers such as APTA12. The conjugation can lead to selectively accumulate in the cancer cells thus decreasing its potential nonspecific as well as cardiotoxic side effects. The aim of this study was to prepare a conjugate of DOX with APTA12 and assess the chemotherapeutic properties of the conjugate specific to cancer cells. The DOX-APTA12 conjugate was prepared by incubation and its cytotoxicity in MCF-10A (non-cancerous mammary cells) and MDA-MB-231 (breast cancer cells) was assessed. The results indicate that DOX-APTA12 conjugate is a potential option for chemotherapy especially for nucleolin expressing breast cancer with reduced doxorubicin associated side effects.


Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/patologia , Desoxicitidina/análogos & derivados , Doxorrubicina/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/química , Desoxicitidina/metabolismo , Desoxicitidina/farmacologia , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo
12.
Mater Sci Eng C Mater Biol Appl ; 105: 110051, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546341

RESUMO

We describe herein a chitosan nanocarrier for drug delivery applications obtained through the self-assembly of carboxymethyl-hexanoyl chitosan and dodecyl sulfate (CHC-SDS). Nanocapsules with spherical morphology were obtained in phosphate buffer at pH 7.4. These CHC-SDS nanocapsules showed no toxicity toward Jurkat cells (acute lymphoblastic leukemia) and were used to encapsulate a new pyrazoline (H3TM04) with antileukemia activity. The samples were characterized by dynamic light scattering (DLS) and Laser Doppler Micro-Electrophoresis. The encapsulation efficiency was higher than 96% (293.6 µg mL-1) and the H3TM04-loaded nanocapsules (CHC-SDS-H) had a negative surface charge (-29.8 ±â€¯0.7 mV) and hydrodynamic radius of around 84 nm. For the first time, CHC-SDS-H were formed and the antitumoral cancer activity was proved. The in vitro assays showed the controlled release of H3TM04 from the CHC-SDS-H nanocapsules in phosphate buffer pH 7.4. The H3TM04 release data were described by the power law model, indicating that H3TM04 delivery occurred via an erosion mechanism. The cytotoxicity assays with Jurkat and K-562 cells (acute myeloid leukemia) demonstrated that the CHC-SDS-H nanocapsule decreases the half maximal inhibitory concentration (IC50). The study showed that CHC-SDS nanocapsules represent a promising nanocarrier for pyrazoline derivates that could be applied in leukemia therapy.


Assuntos
Antineoplásicos , Portadores de Fármacos , Leucemia/tratamento farmacológico , Nanopartículas , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Células Jurkat , Células K562 , Leucemia/metabolismo , Leucemia/patologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Dodecilsulfato de Sódio/química , Dodecilsulfato de Sódio/farmacocinética , Dodecilsulfato de Sódio/farmacologia
13.
Mater Sci Eng C Mater Biol Appl ; 105: 110052, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546360

RESUMO

Novel duck reovirus (NDRV) disease is a serious infectious disease for poultry, for which no effective therapy has been established. Therefore, development of novel antivirals against NDRV is urgently needed. In present study, we developed a complex wherein hypericin (HY), which shows broad-spectrum antiviral activity, was loaded onto graphene oxide (GO), which has a high drug-loading capacity and low cytotoxicity. The antiviral activity of the complex (GO/HY) was studied in DF-1 cells and in ducklings infected with the NDRV TH11 strain. GO/HY showed a dose-dependent inhibition of NDRV replication, which may be attributed to direct virus inactivation or inhibition of virus attachment. Western blotting and indirect immunofluorescence assay (IFA) showed markedly suppressed protein expression in GO/HY-treated NDRV-infected DF-1 cells. Moreover, GO/HY prolonged the survival time of the ducklings by reducing pathological lesions caused by the infection and inhibiting viral replication in the liver and lungs. These results suggest that GO/HY has antiviral activity against NDRV both in vitro and in vivo.


Assuntos
Portadores de Fármacos , Patos , Grafite , Orthoreovirus Aviário/metabolismo , Perileno/análogos & derivados , Doenças das Aves Domésticas , Infecções por Reoviridae , Animais , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Patos/metabolismo , Patos/virologia , Grafite/química , Grafite/farmacologia , Perileno/química , Perileno/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia , Infecções por Reoviridae/tratamento farmacológico , Infecções por Reoviridae/metabolismo , Infecções por Reoviridae/patologia , Infecções por Reoviridae/veterinária
14.
Mater Sci Eng C Mater Biol Appl ; 105: 110094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546441

RESUMO

Cancer has emanated as a daunting menace to human-kind even though medicine, science, and technology has reached its zenith. Subsequent scarcity in the revelation of new drugs, the exigency of salvaging formerly discovered toxic drugs such as doxorubicin has emerged. The invention of drug carrier has made drug delivery imminent which is ascribable to its characteristic traits of specific targeting, effective response to stimuli and biocompatibility. In this paper, the nanoscale polymeric drug carrier poly(N,N-diethyl acrylamide) nanohydrogel has been synthesized by inverse emulsion polymerization. Lower critical solution temperature of the polymeric carrier has been modified using graphene quantum. The particle size of pure nanohydrogel was in the range of 47 to 59.5 nm, and graphene quantum dots incorporated nanohydrogels was in the range of 68.1 to 87.5 nm. Doxorubicin (hydroxyl derivative of anthracycline) release behavior as a function of time and temperature was analyzed, and the Lower critical solution temperature of the synthesized nanohydrogels has been found to be in the range of 28-42 °C. Doxorubicin release characteristics have improved significantly as the surrounding temperature of the release media was increased near to physiological temperature. Further, the cumulative release profile was fitted in the different kinetic model and found to follow a Fickian diffusion release mechanism. The hydrogel was assessed for its cytotoxicity in B16F10 cells by MTT assay. In-vivo studies were done to study the lung metastasis by melanoma cancer and the results showed a rational favorable prognosis which was confirmed by evaluating hematological parameters and the non-immunogenic nature of nanohydrogel by cytokine assay. Comprehensively, the results suggested that poly(N,N-diethyl acrylamide) nanohydrogels have potential application as an intelligent drug carrier for melanoma cancer.


Assuntos
Acrilamidas , Doxorrubicina , Portadores de Fármacos , Grafite , Hidrogéis , Neoplasias Pulmonares , Neoplasias Experimentais , Pontos Quânticos , Acrilamidas/química , Acrilamidas/farmacocinética , Acrilamidas/farmacologia , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Grafite/química , Grafite/farmacocinética , Grafite/farmacologia , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Metástase Neoplásica , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico
15.
Mater Sci Eng C Mater Biol Appl ; 105: 110047, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546452

RESUMO

An amphiphilic star-shaped copolymer ß-CD-g-PCL-SS-PEG-FA, consisting of a ß-cyclodextrin (ß-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, ß-CD was utilized as core to growth PCL arms by ring-opening polymerization (ROP) of ε-CL, before disulfide terminal group transformation to render ß-CD-g-PCL-SS-COOH. Secondly, α-hydroxy-ω-amine protected PEG (HO-PEG-NHBoc) was connected to ß-CD-g-PCL-SS-COOH to obtain amphiphilic ß-CD-g-PCL-SS-PEG, where PCL and PEG were connected via bioreducible disulfide bond. After deprotection of -Boc group, FA was introduced onto the distal end of block arms to obtain the desired ß-CD-g-PCL-SS-PEG-FA copolymer. Because of highly branched core-shell amphiphilic structures, ß-CD-g-PCL-SS-PEG-FA could act as unimolecular micelles. Interestingly, this unimolecular micelle could release the encapsulated drug in a glutathione (GSH) dependent manner due to disulfide linkage. More importantly, this unimolecular micelle could load doxorubicin (DOX) to promote its cellular uptake in multidrug resistance (MDR) protein overexpression tumor cells, by taking the advantage of FA targeting group and intracellular high GSH level in cancer cells. Together with satisfactory biocompatibility, this novel star-like ß-CD-g-PCL-SS-PEG-FA unimolecular micelle could potentially be utilized as targeting nanocarriers in drug resistant cancer therapy.


Assuntos
Doxorrubicina , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Micelas , Neoplasias/tratamento farmacológico , beta-Ciclodextrinas , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Células Hep G2 , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacocinética , beta-Ciclodextrinas/farmacologia
16.
Carbohydr Polym ; 224: 115161, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472854

RESUMO

Electroactive scaffolds derived from carbohydrate hydrogels were synthesized, resulting in a large shift in the conductivity of chitosan (CS) from 10-6 S/cm to about 10-3 S/cm, assigned to CS-oligoaniline. Several analyses including UV-vis spectroscopy and cyclic voltammetry were performed, before examining the carbohydrate-based scaffolds for their ability to recapitulate the neural tissue microenvironment. Good conductivity and resemblance of the modulus to soft tissue of the optimized hydrogels led to appropriate cellular activity and neural regeneration. The loss of dopaminergic neurons as the prominent source of dopamine in the central nervous system results in the deterioration of multiple brain functions such as voluntary movement and behavioral processes. To overcome this, olfactory ecto-mesenchymal stem cells (OE-MSCs) were induced to differentiate into dopaminergic neuron-like cells on hydrogels through a monolayer arrangement cell culture by using cocktail neurotrophic factors including sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). The differentiation capacity of a series of OE-MSCs on the conductive hydrogel was evaluated by real-time PCR, immunocytochemistry and flow cytometry, and the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) neural and dopaminergic markers. The results of this study represent the first steps in designing and implementing advanced platforms based on conductive polysaccharide hydrogels for neural disorder therapies, such as the treatment of Parkinson's disease.


Assuntos
Alginatos/química , Quitosana/química , Portadores de Fármacos/química , Condutividade Elétrica , Hidrogéis/química , Doenças do Sistema Nervoso/terapia , Sefarose/química , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/citologia , Portadores de Fármacos/farmacologia , Humanos , Hidrogéis/farmacologia , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Doenças do Sistema Nervoso/patologia , Mucosa Olfatória/citologia
17.
ACS Appl Mater Interfaces ; 11(37): 33667-33675, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31414601

RESUMO

In an attempt to develop an imaging probe with ultra-high sensitivity for a broad range of tumors in vivo and inspired by the concept of chemical synthetic nanoreactors, we designed a type of glutathione-priming fluorescent nanoreactor (GPN) with an albumin-coating shell and hydrophobic polymer core containing disulfide bonds, protonatable blocks, and indocyanine green (ICG), a near-infrared fluorophore. The albumin played multiple roles including biocompatible carriers, hydrophilic stabilizer, "receptor" of the fluorophores, and even targeting molecules. The protonation of the hydrophobic core triggered the outside-to-core transport of acidic glutathione (GSH), as well as the core-to-shell transference of ICGs after the disulfide bond cleavage by GSH, which induced strong binding of fluorophores with albumins on the GPN shell, initiating intensive fluorescence signals. As a result, the GPNs demonstrated extremely high response sensitivity and imaging contrast, proper time window, and broad cancer specificity. In fact, an orthogonal activation pattern was found in vitro with an ON/OFF ratio up to 24.7-fold. Furthermore, the nanoprobes specifically amplified the tumor signals in five cancer-bearing mouse models and actualized tumor margin delineation with a contrast up to 20-fold, demonstrating much better imaging efficacy than the other four commercially available probes. Therefore, the GPNs provide a new paradigm in developing high-performance bioresponsive nanoprobes.


Assuntos
Portadores de Fármacos , Glutationa/metabolismo , Verde de Indocianina , Nanopartículas , Neoplasias Experimentais/diagnóstico por imagem , Imagem Óptica , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Células HT29 , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia
18.
ACS Appl Mater Interfaces ; 11(37): 33659-33666, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31436085

RESUMO

Surface modification with oligonucleotides renders gold nanoparticles to endocytose through very different pathways as compared to unmodified ones. Such oligonucleotide-modified gold nanoparticles (OGNs) have been exploited as effective nanocarriers for gene regulation therapies. Notably, in an effort to reduce overall dosage and provide safer transition to the clinic, cooperative systems composed of two or more discrete nanomaterials have been recently proposed as an alternative to intrinsically multifunctional nanoparticles. Yet, our understanding of such systems designed to synergistically cooperate in their diagnostic or therapeutic functions remains acutely limited. Specifically, cellular interactions and uptake of OGNs are poorly understood when the cell simultaneously interacts with other types of nanoparticles. Here, we investigated the impact of simultaneous uptake of similar-sized iron oxide nanoparticles (IOPs) on the endocytosis and gene regulation function of OGNs, whose analogues have been proposed for sensitization, targeting, and treatment of tumors. We discovered that both the OGN uptake amount and, remarkably, the gene regulation function remained stable when exposed to a very wide range of extracellular concentrations of IOPs. Additionally, the co-localization analysis showed that a proportion of OGNs was co-localized with IOPs inside cells, which hints at the presence of similar trafficking pathways for OGNs and IOPs following endocytosis. Taken together, our observations indicate that while the OGN endocytosis is highly independent of the IOP endocytosis, it shares transport pathways inside cells-but does so without affecting the gene regulation behavior. These results provide key insights into concomitant interactions of cells with diverse nanoparticles and offer a basis for the future design and optimization of cooperative nanomaterials for diverse theranostic applications.


Assuntos
Portadores de Fármacos , Endocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ouro , Nanopartículas Metálicas , Oligonucleotídeos , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ouro/química , Ouro/farmacocinética , Ouro/farmacologia , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Células NIH 3T3 , Oligonucleotídeos/química , Oligonucleotídeos/farmacocinética , Oligonucleotídeos/farmacologia
19.
J Colloid Interface Sci ; 556: 258-265, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450020

RESUMO

Layered double hydroxide nanoparticles (LDHs) have shown the excellent capability and good adjuvant function as a nanocarrier for protein antigen delivery to enhance the immune response. Furthermore, LDHs have good biocompatibility and low cytotoxicity. However, their oral vaccine delivery efficiency is limited due to acidic/enzyme degradation in the stomach and low bioavailability in the small intestine. To overcome these challenges, alginate-chitosan coated LDHs nanocomposites (ALG-CHT-LDH) have been developed and used as a carrier for oral protein vaccine delivery. The physicochemical properties of ALG-CHT-LDH have been determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and ultraviolet visible (UV-Vis) spectroscopy. Protein release properties of LDHs with/without polymer coating have been investigated at various pHs. The protein release profile of ALG-CHT-LDH nanocomposites indicated that ALG-CHT coating could partially protect protein release at the acidic condition (pH 1.2). The cellular uptake efficiency of protein delivered by ALG-CHT-LDH for the intestine cells and macrophages were studied. After alginate layer falls from ALG-CHT-LDH nanocomposite, flow cytometry analysis (FACS) data suggest that chitosan-coated LDHs significantly enhance the internalization of proteins at the Caco2 and macrophage cells.


Assuntos
Alginatos , Quitosana , Portadores de Fármacos , Hidróxidos , Nanocompostos , Vacinas , Administração Oral , Alginatos/química , Alginatos/farmacologia , Animais , Células CACO-2 , Quitosana/química , Quitosana/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células HT29 , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Camundongos , Nanocompostos/química , Nanocompostos/uso terapêutico , Células RAW 264.7 , Vacinas/química , Vacinas/farmacologia
20.
ACS Appl Mater Interfaces ; 11(37): 34268-34281, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31454217

RESUMO

A multifunctional diagnosis and treatment integration platform is crucial in cancer treatments. Here, we show that by integrating Gd-doped silicon nanoparticles (Si-Gd NPs), chlorine e6 (Ce6), doxorubicin (DOX), zeolitic imidazolate framework-8 (ZIF-8), poly(2-(diethylamino)ethyl methacrylate) polymers (HOOC-PDMAEMA-SH), and folic acid-poly(ethylene glycol)-maleimide (MaL-PEG-FA) into one single nanoplatform by a self-assembly method, novel multifunctional MOFs (named FZIF-8/DOX-PD-FA) are synthesized with great biocompatibility and tumor targeting as well as pH responsiveness and no drug leakage for drug delivery. In the design, Si-Gd NPs and Ce6 embedded in the nanocomposites are used for magnetic resonance and fluorescence dual-modal imaging, respectively. DOX loaded by the FZIF-8/DOX-PD-FA porous structure is used for chemotherapy, while Ce6 is excited by near-infrared radiation (NIR) for photodynamic therapy. In addition, the pH-responsive ability of HOOC-PDMAEMA-SH to effectively prevent drug leakage is demonstrated by drug release studies in vitro. From the results of confocal microscopy imaging in vitro and fluorescence/magnetic resonance imaging in vivo, FZIF-8/DOX-PD-FA showed a targeting effect on MCF-7 cancer cells. More importantly, the results of treatment experiments on tumor-bearing mice showed that the tumor volume of the FZIF-8/DOX-PD-FA + NIR group is decreased the most compared to the original volume. Owing to the unique dual-modal imaging capability and excellent chemo-/photodynamic combinational cancer therapy effect, the present hybrid nanocarrier provides a new research platform for a new generation of theranostic nanoparticles.


Assuntos
Doxorrubicina , Portadores de Fármacos , Imagem por Ressonância Magnética , Nanocompostos , Neoplasias Experimentais , Imagem Óptica , Fotoquimioterapia , Células A549 , Animais , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Camundongos Nus , Nanocompostos/química , Nanocompostos/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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