RESUMO
A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.
Assuntos
Portadores de Fármacos/química , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Animais , Glicemia/metabolismo , Hipóxia Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Liberação Controlada de Fármacos , Glucose Oxidase/metabolismo , Células HeLa , Humanos , Hipoglicemiantes/química , Insulina/química , Masculino , Camundongos Endogâmicos C57BL , Nitroimidazóis/química , Oxirredução , Peptídeos/química , Polietilenoglicóis/químicaRESUMO
Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrared (NIR) imaging, two-photon (TP) imaging, photoacoustic (PA) imaging, and multimodal (MM) imaging, are introduced. Then, CPN-based photodynamic therapy (PDT) and photothermal therapy (PTT) are surveyed. A variety of stimuli-responsive CPN systems for drug delivery are also summarized, and the promising trends and translational challenges are discussed.
Assuntos
Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Polímeros/química , Nanomedicina Teranóstica , FotoquimioterapiaRESUMO
Greatly enhanced energy density in poly(vinylidene fluoride-chlorotrifluoroethylene) [P(VDF-CTFE)] is realized through interface effects induced by a photo cross-linking method. Being different from nanocomposites with lowered dielectric strength, the cross-linked P(VDF-CTFE)s possess a high breakdown field as well as remarkably elevated polarization, both of which contribute to the enhanced energy density as high as 22.5 J · cm(-3). Moreover, patterned thin films with various shapes and sizes are fabricated by photolithography, which sheds new light on the integration of PVDF-based electroactive polymers into organic microelectronic devices such as flexible pyroelectric/piezoelectric sensor arrays or non-volatile ferroelectric memory devices.
Assuntos
Clorofluorcarbonetos/química , Reagentes de Ligações Cruzadas/química , Polímeros/química , Polivinil/química , Varredura Diferencial de Calorimetria , Transferência de Energia , Processos Fotoquímicos , Temperatura , TermodinâmicaRESUMO
The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Encéfalo/citologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Fenômenos Eletromagnéticos , Plasticidade Neuronal/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Nanopartículas/química , Tirosina 3-Mono-Oxigenase/metabolismo , Ondas Ultrassônicas , Tecnologia sem Fio , Peixe-ZebraRESUMO
A high-optical-resolution artificial retina system that accurately communicates with the optic nerve is the main challenge in the modern biological science and bionic field. Here, we developed a bionic artificial retina possessing phototransduction "cells" with measurements even smaller than that of the neural cells. Using the technique of micrometer processing, we constructed a pyramid-shape periodic microarray of a photoreceptor. Each "sensing cell" took advantage of polythiophene derivative/fullerene derivative (PCBM) as a photoelectric converter. Because folic acid played an essential role in eye growth, we particularly modified the polythiophene derivatives with folic acid tags. Therefore, the artificial retina could enlarge the contact area and even recognize the nerve cells to improve the consequence of nerve stimulation. We implanted the artificial retina into blinded rats' eyes. Electrophysiological analysis revealed its recovery of photosensitive function 3 months after surgery. Our work provides an innovative idea for fabricating a high-resolution bionic artificial retina system. It shows great potential in artificial intelligence and biomedicine.
Assuntos
Biônica , Polímeros/química , Retina , Animais , Ácido Fólico/química , Próteses e Implantes , Ratos , Tiofenos/químicaRESUMO
Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.
Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Insulina/administração & dosagem , Polímeros/química , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/síntese química , Camundongos , Estrutura Molecular , Polímeros/síntese química , SuínosRESUMO
Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 µg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application.
Assuntos
Diagnóstico por Imagem/métodos , Nanopartículas de Magnetita/química , Sondas Moleculares/química , Neoplasias/diagnóstico , Polímeros/química , Espectrometria de Fluorescência/métodos , Morte Celular , Linhagem Celular Tumoral , Cor , Endocitose , Corantes Fluorescentes/química , Humanos , Nanopartículas de Magnetita/ultraestruturaRESUMO
A light-activated hypoxia-responsive conjugated polymer-based nanocarrier is developed for efficiently producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargoes in tumor cells, leading to enhanced antitumor efficacy. This dual-responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug-release modality.
Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Luz , Nanopartículas/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imagem Óptica , Álcool de Polivinil/química , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Transplante HeterólogoRESUMO
A bioinspired photodetector with signal transmissible to neuron cells is fabricated. Photoisomerization of the dye molecules embedded in the ferroelectric polymer membrane achieves electric polarization change under visible light. The photodetector realizes high sensitivity, color recognition, transient response, and 3D visual detection with resolution of 25 000 PPI, and, impressively, directly transduces the signal to neuron cells.
Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Neurônios/citologia , Neurônios/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Animais , Cor , Corantes/química , Corantes/efeitos da radiação , Eletricidade , Isomerismo , Luz , Células PC12 , RatosRESUMO
A multifunctional nanocarrier for encapsulation and delivery of short interfering RNA (siRNA) has been realized using cationic fluorescent polymer core-shell nanoparticles. The nanocarrier has good biocompatibility and high transfection efficiency over the most popular transfection reagent, Lipofectamine 2000. Fluorescence resonance energy transfer within the nanocarrier provides a non-invasive and label-free method to track the intracellular release of siRNA.
Assuntos
Portadores de Fármacos/química , Corantes Fluorescentes/química , Espaço Intracelular/metabolismo , Nanopartículas/química , Polímeros/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Cápsulas , Desenho de Fármacos , Liberação Controlada de Fármacos , Células HeLa , Células Hep G2 , HumanosRESUMO
Nanoscale materials are now attracting a great deal of attention for biomedical applications. Conjugated polymer nanoparticles have remarkable photophysical properties that make them highly advantageous for biological fluorescence imaging. We report on conjugated polymer nanoparticles with phenylboronic acid tags on the surface for fluorescence detection of neurotransmitter dopamine in both living PC12 cells and brain of zebrafish larvae. The selective enrichment of dopamine and fluorescence signal amplification characteristics of the nanoparticles show rapid and high-sensitive probing such neurotransmitter with the detection limit of 38.8 nM, and minimum interference from other endogenous molecules. It demonstrates the potential of nanomaterials as a multifunctional nanoplatform for targeting, diagnosis, and therapy of dopamine-relative disease.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Nanopartículas/química , Polímeros/química , Peixe-Zebra/metabolismo , Animais , Ácidos Borônicos/química , Difusão Dinâmica da Luz , Corantes Fluorescentes/química , Larva/metabolismo , Luz , Microscopia Confocal , Nanopartículas/metabolismo , Células PC12 , Polímeros/síntese química , Ratos , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.
Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Ácido Fólico , Nanopartículas , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Ácido Fólico/administração & dosagem , Ácido Fólico/química , Glutationa/química , Células HeLa , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/química , Oxirredução , Peptídeos/química , Polietilenoglicóis/químicaRESUMO
The present study describes a flexible nanoplatform based on electrostatic assembly of conjugated polyelectrolytes (CPEs) and carboxylated multi-walled carbon nanotubes (cMWNTs). It is demonstrated that the obtained nanocomposites inherit intrinsic optical properties of CPEs and characteristic Raman vibration modes of MWNTs, providing a fluorescence-Raman dual-imaging method for intracellular tracking and locating of MWNTs. We suggest that the cellular internalization of the CPE-cMWNT nanocomposites is a surface charge-dependent process. The strengths of this nanoplatform include satisfying biocompatibility, enhanced protein-repellent property, and ease of implementation, making it available for both in vitro and in vivo applications.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Eletrólitos/química , Nanotubos de Carbono/química , Polímeros/química , Análise Espectral Raman/métodos , Adsorção , Animais , Materiais Biocompatíveis , Carbono/química , Linhagem Celular Tumoral , Citocromos c/química , Sistemas de Liberação de Medicamentos , Hemoglobinas/química , Cavalos , Humanos , Microscopia de Fluorescência , Nanocompostos/química , Nanotecnologia , Óptica e Fotônica , Eletricidade EstáticaRESUMO
Dextran modified with pendant acetals is used to load doxorubicin (DOX) and a near-infrared-emissive conjugated polymer (BTTPF), and this aims to provide selective drug release at therapeutic targets including tumors. The BTTPF is applicable to tracking the anticancer drug release through the change of Förster resonance energy transfer efficiency between doxorubicin and BTTPF during degradation of the nanoparticles in vivo.
Assuntos
Doxorrubicina/análise , Sistemas de Liberação de Medicamentos/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/análise , Nanopartículas/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/farmacocinética , Concentração de Íons de Hidrogênio , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Polímeros/administração & dosagem , Polímeros/análise , Polímeros/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Composite nanoparticles with magnetic core and fluorescent shell were facilely prepared by the layer-by-layer deposition of conjugated polyelectrolytes over the negatively charged nanoparticles (NPs) of superparamagnetic iron oxide. The alternate assembly of cationic and anionic fluorescent polyelectrolytes leads to reversal in the sign of zeta-potentials. The even numbers of adsorption layer corresponding to the anionic polyelectrolyte (PFS) have negative values (-13 to -24 mV), whereas odd numbers of coating relative to the cationic polyelectrolyte (PFN) have positive values (26 to 28 mV). The composite nanoparticles can respond to both external magnetic field and ultraviolet light excitation. Forster resonance energy transfer (FRET) between oppositely charged polyelectrolytes (PFN and ThPFS) layers was also found, indicating dense packing of the polymer coatings. The fluorescence of the positively charged nanoparticles (NPs/PFN) can be quenched with very high efficiency by a small molecule anionic quencher [Fe(CN)6(4-)], while the same quencher has far less effect on the fluorescence of the negatively charged nanoparticles (NPs/PFN/PFS).