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1.
Indian J Gastroenterol ; 42(6): 791-799, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37610566

RESUMO

BACKGROUND: The purpose of this study was to understand the experiences of primary caretakers (PCTs) with a child diagnosed with celiac disease (CeD). There is paucity of research in understanding the experiences of PCTs of children with CeD in India. METHODS: Purposive sampling was used to select PCTs of CeD-affected children from a tertiary hospital in New Delhi. Ten PCTs took part in the investigation. To gather the data, semi-structured interviews were held with participants. Hindi was used to administer the interviews. RESULTS: The current study focused on the difficulties and worries PCTs experience in managing CeD. The main themes and sub-themes that emerged from the data were diagnosis of CeD (misdiagnosis of CeD, late diagnosis of CeD, feelings at the time of diagnosis, help from a doctor/nutritionist at the time of diagnosis); characteristics of CeD (CeD as a new disease, CeD as an allergy); attitude towards wheat (wheat as a poison, ignorance regarding negative effect of wheat); influence of significant others (making fun of the child, queries from others are a source of worry, non-acceptance of celiac disease by others and pressure to give gluten to the child); issues in following gluten-free diet (GFD) (fear of cross-contamination, distrust on GFD available outside home, GFD is expensive, making GFD is difficult, joint family, non-adherence to GFD, making non-GFD along with GFD); effect of CeD (financial effect of CeD, effect on physical and mental health of the child and PCT, effect on social life, change in family dynamics, eating restrictions); management of CeD (GFD for the whole family to manage CeD, family support to manage CeD, adhering to GFD, early diagnosis); and concerns (future marital concern for the child, cure of CeD, proper physical growth). CONCLUSION: The current study gave an understanding of how PCTs dealt with a child's CeD. The difficulties and worries of caretakers should be taken into consideration and appropriate recommendations made to lessen the strain of managing the child's CeD and the daily obstacles associated with it.


Assuntos
Doença Celíaca , Hipersensibilidade , Criança , Humanos , Doença Celíaca/complicações , Dieta Livre de Glúten/psicologia , Projetos de Pesquisa , Índia , Cooperação do Paciente
2.
Nanoscale Adv ; 5(1): 277-289, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36605795

RESUMO

Clinically used small-molecular photosensitizers (PSs) for photodynamic therapy (PDT) share similar disadvantages, such as the lack of selectivity towards cancer cells, short blood circulation time, life-threatening phototoxicity, and low physiological solubility. To overcome such limitations, the present study capitalizes on the synthesis of ultra-small hydrophilic porphyrin-based silica nanoparticles (core-shell porphyrin-silica dots; PSDs) to enhance the treatment outcomes of cancer via PDT. These ultra-small PSDs, with a hydrodynamic diameter less than 7 nm, have an excellent aqueous solubility in water (porphyrin; TPPS3-NH2) and enhanced tumor accumulation therefore exhibiting enhanced fluorescence imaging-guided PDT in breast cancer cells. Besides ultra-small size, such PSDs also displayed an excellent biocompatibility and negligible dark cytotoxicity in vitro. Moreover, PSDs were also found to be stable in other physiological solutions as a function of time. The fluorescence imaging of porphyrin revealed a prolonged residence time of PSDs in tumor regions, reduced accumulation in vital organs, and rapid renal clearance upon intravenous injection. The in vivo study further revealed reduced tumor growth in 4T1 tumor-bearing bulb mice after laser irradiation explaining the excellent photodynamic therapeutic efficacy of ultra-small PSDs. Thus, ultrasmall hydrophilic PSDs combined with excellent imaging-guided therapeutic abilities and renal clearance behavior represent a promising platform for cancer imaging and therapy.

3.
ACS Nano ; 15(12): 20164-20180, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34898184

RESUMO

Nanomaterials that combine multimodality imaging and therapeutic functions within a single nanoplatform have drawn extensive attention for molecular medicines and biological applications. Herein, we report a theranostic nanoplatform based on a relatively smaller (<20 nm) iron oxide loaded porphyrin-grafted lipid nanoparticles (Fe3O4@PGL NPs). The amphiphilic PGL easily self-assembled on the hydrophobic exterior surface of ultrasmall Fe3O4 NPs, resulting in a final ultrasmall Fe3O4@PGL NPs with diameter of ∼10 nm. The excellent self-assembling nature of the as-synthesized PGL NPs facilitated a higher loading of porphyrins, showed a negligible dark toxicity, and demonstrated an excellent photodynamic effect against HT-29 cancer cells in vitro. The in vivo experimental results further confirmed that Fe3O4@PGL NPs were ideally qualified for both the fluorescence and magnetic resonance (MR) imaging guided nanoplatforms to track the biodistribution and therapeutic responses of NPs as well as to simultaneously trigger the generation of highly cytotoxic reactive oxygen species (ROS) necessary for excellent photodynamic therapy (PDT). After recording convincing therapeutic responses, we further evaluated the ability of Fe3O4@PGL NPs/Fe3O4@Lipid NPs for ferroptosis therapy (FT) via tumor microenvironment (TME) modulation for improved anticancer activity. We hypothesized that tumor-associated macrophages (TAMs) could significantly improve the efficacy of FT by accelerating the Fenton reaction in vitro. In our results, the Fe ions released in vitro directly contributed to the Fenton reaction, whereas the presence of RAW 264.7 macrophages further accelerated the ROS generation as observed by the fluorescence imaging. The significant increase in the ROS during the coincubation of NPs, endocytosed by HT-29 cells and RAW264.7 cells, further induced increased cellular toxicity of cancer cells.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Compostos Férricos , Humanos , Lipossomos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Distribuição Tecidual , Microambiente Tumoral
4.
ACS Nano ; 14(10): 13569-13583, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32915537

RESUMO

Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both in vitro and in vivo results demonstrated that the obtained O2@PFOB@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of O2@PFOB@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the O2@PFOB@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.


Assuntos
Neoplasias do Colo , Fluorocarbonos , Neoplasias Hepáticas , Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Hipóxia Tumoral
5.
J Nanosci Nanotechnol ; 20(12): 7618-7628, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711634

RESUMO

The emergence of bacterial resistance to currently available antibiotics emphasized the urgent need for new antibacterial agents. Nanotechnology-based approaches are substantially contributing to the development of effective and better-formulated antibiotics. Here, we report the synthesis of stable manganese oxide nanostructures (MnO NS) by a facile, one-step, microwave-assisted method. Asprepared MnO NS were thoroughly characterized by atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), UV-Visible spectroscopy and X-ray powder diffraction (XRD). UV-Visible spectra give a sharp absorption peak at a maximum wavelength of 430 nm showed surface plasmon resonance (SPR). X-ray diffraction (XRD) profile demonstrated pure phase and crystalline nature of nanostructures. Morphological investigations by a scanning electron microscope showed good dispersity with spherical particles possessing a size range between 10-100 nm. Atomic force microscope data exhibited that the average size of MnO NS can be controlled between 25 nm to 150 nm by a three-fold increment in the amount of stabilizer (o-phenylenediamine). Antimicrobial activity of MnO NS on both gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacterial strains showed that prepared nanostructures were effective against microorganisms. Further, this antibacterial activity was found to be dependent on nanoparticles (NPs) size and bacterial species. These were more effective against Bacillus subtilis (B. subtilis) as compared to Escherichia coli (E. coli). Considering the results together, this study paves the way for the formulation of similar nanostructures as effective antibiotics to kill other pathogens by a more biocompatible platform. This is the first report to synthesize the MnO NS by green approach and its antibacterial application.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Antibacterianos/farmacologia , Escherichia coli , Compostos de Manganês , Testes de Sensibilidade Microbiana , Óxidos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
6.
Theranostics ; 10(5): 2130-2140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104501

RESUMO

Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and "always-on" properties of the conventional fluorescent probes leads to high background signals and poor specificity. Method: To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes (ss-diCy5 and ss-diNH800CW) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. Results: The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. In vivo xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. Conclusion: In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.


Assuntos
Dissulfetos/química , Glutationa/metabolismo , Neoplasias/metabolismo , Imagem Óptica/métodos , Animais , Corantes/química , Corantes/metabolismo , Diagnóstico por Imagem/métodos , Feminino , Corantes Fluorescentes/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Técnicas de Sonda Molecular/instrumentação , Neoplasias/diagnóstico por imagem , Imagem Óptica/tendências , Microambiente Tumoral/efeitos dos fármacos
7.
Colloids Surf B Biointerfaces ; 188: 110775, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958619

RESUMO

Combining nanomaterials in varying morphology and functionalities gives rise to a new class of composite materials leading to innovative applications. In this study, we designed a heterostructured hybrid material consisting of two-dimensional bismuth nanosheets augmented by molecularly imprinted networks. Antibiotic overuse is now one of the main concerns in health management, and their monitoring is highly desirable but challenging. So, for this purpose, the resulting composite interface was used as a transducer for quartz crystal microbalances. The main objective was to develop highly selective mass-sensitive sensor for chloramphenicol. Morphological investigation revealed the presence of ultrathin, square shaped nanosheets, 2-3 nm in height and further supplemented by imprinted polymers. Sensor responses are described as the decrease in the frequency of microbalances owing to chloramphenicol re-binding in the templated cavities, yielding a detection limit down to 0.74 µM. This sensor demonstrated a 100 % specific detection of chloramphenicol over its interfering and structural analogs (clindamycin, thiamphenicol, and florfenicol). This composite interface offers the advantage of selective binding and excellent sensitivity due to special heterostructured morphology, in addition to benefits of robustness and online monitoring. The results suggest that such composite-based sensors can be favorable platforms, especially for commercial prospects, to obtain selective detection of other biomolecules of clinical importance.


Assuntos
Materiais Biomiméticos/química , Bismuto/química , Cloranfenicol/análise , Nanoestruturas/química , Polímeros/química , Compostos de Tungstênio/química , Impressão Molecular , Tamanho da Partícula , Técnicas de Microbalança de Cristal de Quartzo , Propriedades de Superfície
8.
Artigo em Inglês | MEDLINE | ID: mdl-31833204

RESUMO

Over the last century, significant progress has been made towards the development of microbubbles (MBs) as a contrast agent for imaging and as a carrier for the delivery of therapeutic moieties. The unparalleled ability of MBs to respond to ultrasound (US) render them advantageous for molecular imaging, and US-responsive targeted delivery. However, the use of MBs has broadened far beyond the imaging contrast agent or drug delivery system alone. Notably, there has been an enormous surge in the design and fabrication of multimodal MBs for cancer therapy. Furthermore, MBs in the presence of the US has unique ability to convert itself from the micro to nanoscale, which offers diagnostic and therapeutic ability in both dimensions. In this review, we summarize the design considerations of MBs, with particular emphasize on their size and composition. In addition, different MBs formulations are discussed in the context of their current progress as an imaging contrast agent and a vehicle for drug/gene delivery. We further highlight recent advancements in the micro-to-nano conversion of MBs and their potential application for cancer theranostics. This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Assuntos
Nanomedicina , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Ultrassonografia , Animais , Diagnóstico por Imagem , Humanos , Microbolhas , Nanopartículas/química , Neoplasias/diagnóstico
9.
Chem Commun (Camb) ; 56(2): 285-288, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31808487

RESUMO

Targeted delivery of chemotherapeutics to tumor cells is one of the biggest challenges in cancer treatment. Herein, we synthesized smart dipeptide nanoparticles for cancer-specific targeting and intracellular pH-sensitive release of chemotherapeutics. Diphenylalanine peptide was synthesized and further developed as nanoparticles (NPs), which were functionalized with folic acid utilizing the carbodiimide reaction. Doxorubicin (Dox) was loaded to self-assembled non-functionalized (FF-Dox) and folate functionalized peptides NPs (FA-FF-Dox). Moreover, the experiments revealed the pH-sensitive release of Dox for both FA-FF-Dox and FF-Dox due to the protonation of the Schiff base and the amines present in the peptides at low pH, enhancing intracellular release subsequent to receptor-mediated endocytosis. Further, biodistribution and the pharmacokinetics study revealed enhanced targeting efficiency of FA-FF-Dox with high accumulation in tumor cells.


Assuntos
Dipeptídeos/química , Portadores de Fármacos/química , Nanopartículas/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Ácido Fólico/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Masculino , Ratos Wistar , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
10.
RSC Adv ; 9(72): 41993-41999, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-35542847

RESUMO

The recent progress in the development of highly biocompatible nanoplatforms mostly encompasses the use of biological excipients such as red blood cells, cancer cell membranes, and also platelets. Such specialized vectors, if mimicked correctly, have intrinsic ability to navigate through the biological system and perform their intended action without eliciting any cascade of inflammatory processes. Naturally, platelets have been found to accumulate in the wound sites and also interact with circulating tumor cells (CTCs). Inspired by the targeting ability of platelets and the clinical success of ultrasound, herein we developed a novel ultrasound contrast agent (UCA) by backfilling of an insoluble gas into the platelets after lyophilization ex vivo. The as-prepared platelet-based ultrasound contrast agent (P-UCA) disguised the structural integrity of the natural platelets with an average diameter of 3.1 ± 0.4 µm, and could enhance the ultrasound signal both in vitro and in vivo. Besides, we further evaluated that such platelet particles could facilitate active loading of ICG molecules for prolonged in vivo fluorescence imaging compared to the free ICG. Taking all the results together, we established that biological structures such as platelets could be repurposed ex vivo as a"shell" to encapsulate gas and be further extended to load ICG for real-time ultrasound and fluorescence imaging respectively. This not only indicates many potential uses of these MBs in the diagnosis of platelet-related diseases, such as vascular damage, thrombosis, and atherosclerosis, but also serves as a powerful platform with multimodal theranostic capability after active loading of a variety of therapeutic and diagnostic agents.

11.
Bioconjug Chem ; 30(1): 13-28, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30508381

RESUMO

For SLN lymph node biopsy (SLNB), SLN mapping has become a standard of care procedure that can accurately locate the micrometastases disseminated from primary tumor sites to the regional lymph nodes. The broad array of SLN mapping has prompted the development of a wide range of SLN tracers, rationally designed for noninvasive and high-resolution imaging of SLNs. At present, conventional SLN imaging probes (blue dyes, radiocolloids, and few other small-molecular dyes), although serving the clinical needs, are often associated with major issues such as insufficient accumulation in SLN, short retention time, staining of the surgical field, and other adverse side effects. In a recent advancement, newly designed fluorescent nanoprobes are equipped with novel features that could be of high interest in SLN mapping such as (i) a unique niche that is not met by any other conventional SLN probes, (ii) their adoptable synthesis method, and (ii) excellent sensitivity facilitating high resolution SLN mapping. Most importantly, lots of effort has been devoted for translating the fluorescent nanoprobes into a clinical setup and also imparting the multimodal imaging abilities of nanoprobes for the excellent diagnosis of life-threatening diseases such as cancer. In this review, we will provide a detailed roadmap of the progress of a wide variety of current fluorescent molecular probes and emphasize the future of nanomaterial-based single/multimodal imaging probes that have true potential translation abilities for SLN mapping.


Assuntos
Corantes Fluorescentes/química , Sondas Moleculares/química , Biópsia de Linfonodo Sentinela/métodos , Animais , Humanos , Verde de Indocianina/química , Metástase Linfática , Micrometástase de Neoplasia , Teoria Quântica , Linfonodo Sentinela/patologia , Solubilidade
12.
J Hazard Mater ; 367: 205-214, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30594721

RESUMO

Development of 1D nanostructures with novel morphology is a recent scientific attraction, so to say yielding unusual materials for advanced applications. In this work, we have prepared solution grown, single-pot 1D ZnWO4 nanowires (NWs) and the morphology is assessed for label-free but selective detection of chloramphenicol. This is the first report where, such structures are being investigated for this purpose. Transmission electron microscopy shows the presence of strands of ZnWO4 of about 20 nm in diameter. The formed NWs were highly dispersed in nature with uniform size and shape. X-ray diffraction analysis confirmed high purity of the designed NWs despite solution synthesis. X-ray photoelectron spectroscopy confirmed surface valence state of ZnWO4. Fourier transform infrared spectroscopy was employed for the ascription of functional groups, whereas, optical properties were investigated using photoluminescence. NWs were employed for the detection of a model antibiotic, chloramphenicol. The developed sensor exhibited excellent limit of detection, 0.32 µM and 100% specificity as compared to its structural and functional analogues such as thiamphenicol and clindamycin. This work can broaden new opportunities for the researchers to explore unconventional nanomaterials bearing unique morphologies and quantum phenomenon for the label-free detection of other bioanalytes.


Assuntos
Antibacterianos/análise , Cloranfenicol/análise , Nanofios/química , Compostos de Tungstênio/química , Compostos de Zinco/química , Antibacterianos/química , Catálise , Cloranfenicol/química , Técnicas Eletroquímicas , Soluções
13.
Theranostics ; 8(19): 5501-5518, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555560

RESUMO

The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy. Methods: A relatively simple and inexpensive rapid injection method was used to prepare porphyrin-grafted lipid (PGL) NPs. The self-assembled PGL NPs were used further to encapsulate DOX via a pH-gradient loading protocol. The self-assembled liposome-like PGL NPs having a hydrophilic core were optimized to load DOX at an encapsulation efficiency (EE) of ~99%. The resultant PGL-DOX NPs were intact, highly stable and importantly these NPs successfully escaped from the endo-lysosomal compartment after laser irradiation to release DOX in the cytosol. The therapeutic efficacy of the aforementioned formulation was validated both in vitro and in vivo. Results: PGL-DOX NPs demonstrated excellent cellular uptake, chemo-photodynamic response, and fluorescence imaging ability in different cell lines. Under laser irradiation, cells treated with a low molar concentration of PGL-DOX NPs reduced cell viability significantly. Moreover, in vivo experiments conducted in a xenograft mouse model further demonstrated the excellent tumor accumulation capability of PGL-DOX NPs driven by the enhanced permeability and retention (EPR) effect. Through fluorescence imaging, the biodistribution of PGL-DOX NPs in tumor and major organs was also easily monitored in real time in vivo. The inherent ability of porphyrin to generate ROS under laser irradiation combined with the cytotoxic effect of the anticancer drug DOX significantly suppressed tumor growth in vivo. Conclusion: In summary, the PGL-DOX NPs combined chemo-photodynamic nanoplatform may serve as a potential candidate for cancer theranostics.


Assuntos
Antibióticos Antineoplásicos/metabolismo , Doxorrubicina/metabolismo , Portadores de Fármacos/química , Corantes Fluorescentes/metabolismo , Lipossomos/química , Porfirinas/metabolismo , Nanomedicina Teranóstica/métodos , Animais , Carcinoma/terapia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Tratamento Farmacológico/métodos , Células HeLa , Xenoenxertos , Humanos , Terapia com Luz de Baixa Intensidade , Camundongos , Nanopartículas/química , Transplante de Neoplasias , Imagem Óptica/métodos , Células PC-3 , Fotoquimioterapia/métodos , Resultado do Tratamento
14.
Bioconjug Chem ; 29(12): 3967-3981, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30485070

RESUMO

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.


Assuntos
Nanomedicina , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Polímeros/farmacologia , Medicina de Precisão
15.
Front Chem ; 6: 127, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721494

RESUMO

Over years, theranostic nanoplatforms have provided a new avenue for the diagnosis and treatment of various cancer types. To this end, a myriad of nanocarriers such as polymeric micelles, liposomes, and inorganic nanoparticles (NPs) with distinct physiochemical and biological properties are routinely investigated for preclinical and clinical studies. So far, liposomes have received great attention for various biomedical applications, however, it still suffers from insufficient morphological stability. On the other hand, inorganic NPs depicting excellent therapeutic ability have failed to address biocompatibility issues. This has raised a serious concern about the clinical approval of multifunctional organic or inorganic-based theranostic agents. Recently, partially silica coated nanohybrids such as cerasomes and bicelles demonstrating both diagnostic and therapeutic ability in a single system, have drawn profound attention as a fascinating novel drug delivery system. Compared with traditional liposomal or inorganic-based nanoformulations, this new and highly stable nanocarriers integrates the functional attributes of biomimetic liposomes and silica NPs, therefore, synergize strengths and functions, or even surpass weaknesses of individual components. This review at its best enlightens the emerging concept of such partially silica coated nanohybrids, fabrication strategies, and theranostic opportunities to combat cancer and related diseases.

16.
Sci China Life Sci ; 61(4): 380-391, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29607461

RESUMO

Tumor microenvironment (TME) comprising cellular and non-cellular components is a major source of cancer hallmarks. Notably, angiogenesis responsible for normal physiological remodeling process can otherwise harness vessel abnormalities during tumorigenesis eliciting severe therapeutic inefficiency. Currently, FDA approved antiangiogenic drugs have only shown modest clinical success owing to tumor hypoxia, antiangiogenic therapeutic resistance, and limited knowledge in understanding TME. In order to overcome these limitations, targeting angiogenesis combined with immunosuppressive TME could offer potential therapeutic opportunities. Indeed, these therapeutic approaches can be further revisited with the advent of nanotechnology that can target the key cellular components of TME and tumor cells more precisely. Synergetic targeting without eliciting systemic toxicity achieved by integration of antiangiogenic and immunotherapy in a single nanoplatform is vital for therapeutic success. In this review, we will discuss the most promising nanotechnological advancements oriented to modulate the immunosuppressive TME in association with antiangiogenic therapy that has gained immense popularity in cancer treatment.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Sistemas de Liberação de Medicamentos/tendências , Imunoterapia , Nanomedicina , Neoplasias/terapia , Neovascularização Patológica/terapia , Microambiente Tumoral , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias/irrigação sanguínea , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Microambiente Tumoral/fisiologia
17.
Nanoscale ; 10(12): 5393-5423, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29528075

RESUMO

Angiogenesis is a normal physiological remodeling process initiated at the time of embryonic development and lessened with the progress of time. Nevertheless, continuous activation of stringent signaling pathways and proangiogenic factors during tumorigenesis (a pathological condition) instigates serious vessel abnormalities eliciting severe therapeutic inefficiency. In principle, systemic delivery of robust antiangiogenic drugs often fails to reach these abnormal tumor vessels depicting poor pharmacokinetics, biodistribution profiles and adverse side effects in vivo. Recently, the advent of nanotechnology has offered numerous advantages encompassing high drug payloads, increased blood half-life and reduced toxicity; likewise, such nanomedicines can also target the key components of the tumor microenvironment and tumor cells effectively. Synergistic targeting of malignant cells and vessel abnormalities via integration of antiangiogenic and other potent combinational regimens in a single nanoplatform can revitalize therapeutic success. In this review, we will discuss the most promising nanotechnological advancements rehabilitating angiogenesis, and emerging nanocarriers comprehending gene delivery, stem cell therapies and dynamic combinational strategies for effective anticancer therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Nanomedicina , Neoplasias/tratamento farmacológico , Portadores de Fármacos , Técnicas de Transferência de Genes , Humanos , Imunoterapia , Neoplasias/terapia , Transplante de Células-Tronco , Distribuição Tecidual , Microambiente Tumoral
18.
J Virol Methods ; 249: 130-136, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28888402

RESUMO

The emergence of nanotechnology has opened new horizons for constructing efficient recognition interfaces. This is the first report where the potential of a multiwalled carbon nanotube based zinc nanocomposite (MWCNTs-Zn NPs) investigated for the detection of an agricultural pathogen i.e. Chili leaf curl betasatellite (ChLCB). Atomic force microscope analyses revealed the presence of multiwalled carbon nanotubes (MWCNTs) having a diameter of 50-100nm with zinc nanoparticles (Zn-NPs) of 25-500nm. In this system, these bunches of Zn-NPs anchored along the whole lengths of MWCNTs were used for the immobilization of probe DNA strands. The electrochemical performance of DNA biosensor was assessed in the absence and presence of the complementary DNA during cyclic and differential pulse voltammetry scans. Target binding events occurring on the interface surface patterned with single-stranded DNA was quantitatively translated into electrochemical signals due to hybridization process. In the presence of complementary target DNA, as the result of duplex formation, there was a decrease in the peak current from 1.89×10-04 to 5.84×10-05A. The specificity of this electrochemical DNA biosensor was found to be three times as compared to non-complementary DNA. This material structuring technique can be extended to design interfaces for the recognition of the other plant viruses and biomolecules.


Assuntos
Begomovirus/isolamento & purificação , Nanocompostos , Nanotecnologia/métodos , Vírus Satélites/isolamento & purificação , Zinco/química , Begomovirus/patogenicidade , Técnicas Biossensoriais , DNA/análise , Técnicas Eletroquímicas , Nanocompostos/química , Nanopartículas , Hibridização de Ácido Nucleico , Doenças das Plantas/virologia , Vírus Satélites/patogenicidade
19.
Biosens Bioelectron ; 89(Pt 2): 822-828, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27816593

RESUMO

This work is the first report describing the development of a novel three dimensional manganese nanostructures based carbon nanotubes (CNTs-Mn NPs) composite, for the determination of ascorbic acid (vitamin C) in pharmaceutical formulation. Carbon nanotubes (CNTs) were used as a conductive skeleton to anchor highly electrolytic manganese nanoparticles (Mn NPs), which were prepared by a hydrothermal method. Scanning electron microscopy and atomic force microscopy revealed the presence of Mn Nps of 20-25nm, anchored along the whole length of CNTs, in the form of patches having a diameter of 50-500nm. Fourier transform infrared spectroscopy confirmed the surface modification of CNTs by amine groups, whereas dynamic light scattering established the presence of positive charge on the prepared nanocomposite. The binding events were studied by monitoring cyclic voltammetry signals and the developed nanosensor exhibited highly sensitive response, demonstrating improved electrochemical activity towards ascorbic acid. Linear dependence of the peak current on the square root of scan rates (R2=0.9785), demonstrated that the oxidation of ascorbic acid by the designed nanostructures is a diffusion control mechanism. Furthermore, linear range was found to be 0.06-4.0×10-3M, and nanosensor displayed an excellent detection limit of 0.1µM (S/N=3). This developed nanosensor was successfully applied for the determination of vitamin C in pharmaceutical formulation. Besides, the results of the present study indicate that such a sensing platform may offer a different pathway to utilize manganese nanoparticles based CNTs composite for the determination of other bio-molecules as well.


Assuntos
Ácido Ascórbico/análise , Técnicas Eletroquímicas/métodos , Manganês/química , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Vitaminas/análise , Eletrodos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Nanotubos de Carbono/ultraestrutura
20.
Bioinorg Chem Appl ; 2014: 135824, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25214825

RESUMO

This study evaluates in vivo and in vitro anti-Helicobacter pylori (H. pylori) efficacy of silver nanoparticles (Ag-NPs) prepared via a cost-effective green chemistry route wherein Peganum harmala L. seeds extract was used as a reducing and capping agent. The structural features, as elucidated by surface plasmon resonance spectrophotometry, transmission electron microscopy, and powder X-ray diffraction spectroscopy, revealed the Ag-NPs synthesized to be polydispersed in nature and spherical in shape with 5-40 nm size. A typical Ag-NPs suspension (S5), with size being 15 nm, when tested in vitro against forty-two local isolates and two reference strains, showed a considerable anti-H. pylori activity. In case of in vivo trial against H. pylori induced gastritis, after oral administration of 16 mg/kg body weight of S5 for seven days, a complete clearance was recorded in male albino rates. In comparative time-killing kinetics, S5 exhibited dose- and time-dependent anti-H. pylori activity that was almost similar to tetracycline and clarithromycin, less than amoxicillin, but higher than metronidazole. Furthermore, S5 was found to be an equally effective anti-H. pylori agent at low (≤4) and high pH with no drug resistance observed even up to 10 repeated exposures while a significant drug resistance was recorded for most of the standard drugs employed. The present results revealed the potential of the synthesized Ag-NPs as safer bactericidal agents for the treatment of H. pylori induced gastritis.

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