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1.
Nanoscale Horiz ; 5(3): 553-563, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118232

RESUMO

Dissipative self-assembly processes were recently exploited to assemble synthetic materials into supramolecular structures. In most cases, chemical fuel or light driven self-assembly of synthetic molecules was reported. Herein, experimental and computational approaches were used to unveil the role of acoustic cavitation in the formation of supramolecular nanoaggregates by dissipative self-assembly. Acoustic cavitation bubbles were employed as an energy source and a transient interface to fuel and refuel the dissipative self-assembly of simple aromatic biomolecules into uniform nanoparticles. Molecular dynamics simulations were applied to predict the formation of metastable aggregates and the dynamic exchange of the interacting molecules in the nanoaggregates. The intracellular trafficking and dissipative dissolution of the nanoparticles were tracked by microscopy imaging.


Assuntos
Simulação de Dinâmica Molecular , Nanopartículas/química , Som , Transporte Biológico , Imagem Molecular , Nanopartículas/efeitos da radiação
2.
Ecotoxicol Environ Saf ; 193: 110332, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32088550

RESUMO

Aggregation of C60, as an important process governing its mobility and toxicity, has been quantitatively investigated. However, effects of sunlight and agitation intensity on the aggregation behavior of aqu/nC60 produced via extended mixing, have not been clarified. Therefore, in the present study, the aggregation behavior of aqu/nC60 produced at 500 and 800 rpm in the absence and presence of sunlight was investigated. Aggregation with increasing concentrations could be accelerated, while changes of Zave and zeta potential were not obvious. Critical coagulation concentrations (CCCs) of aqu/nC60 obtained at 800 rpm in the absence/presence of sunlight and that at 500 rpm under sunlight were 330, 205 and 170 mM NaCl, and 10.0, 2.6 and 3.1 mM CaCl2, respectively. These CCCs indicated that the aqu/nC60 prepared by the extended mixing were more stable than those produced by other methods. Salt-induced aggregation occurred more easily for aqu/nC60 formed under sunlight than that formed in the dark. Extra surface oxidation induced by high agitation intensity remarkably increased the stability of aqu/nC60 in NaCl solutions. In contrast, in CaCl2 solutions, aqu/nC60 formed at high agitation intensity had similar stability or even inadequate stability to that obtained at low agitation intensity due to the charge neutralization and cross-link bridging.


Assuntos
Fulerenos/química , Nanopartículas/química , Luz Solar , Fulerenos/efeitos da radiação , Nanopartículas/efeitos da radiação , Cloreto de Sódio/química
4.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
5.
Int J Pharm ; 572: 118733, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31689481

RESUMO

Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30-70 kDa with a presumably safer low molecular mass PVA 9-10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Doxorrubicina/administração & dosagem , Glioblastoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/efeitos da radiação , Doxorrubicina/química , Doxorrubicina/efeitos da radiação , Desenvolvimento de Medicamentos , Estabilidade de Medicamentos , Masculino , Nanopartículas/química , Nanopartículas/efeitos da radiação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/efeitos da radiação , Ratos Wistar , Esterilização
6.
Nat Commun ; 10(1): 4586, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594932

RESUMO

Upconversion nanoparticles (UCNPs) are the preferred choice for deep-tissue photoactivation, owing to their unique capability of converting deep tissue-penetrating near-infrared light to UV/visible light for photoactivation. Programmed photoactivation of multiple molecules is critical for controlling many biological processes. However, syntheses of such UCNPs require epitaxial growth of multiple shells on the core nanocrystals and are highly complex/time-consuming. To overcome this bottleneck, we have modularly assembled two distinct UCNPs which can individually be excited by 980/808 nm light, but not both. These orthogonal photoactivable UCNPs superballs are used for programmed photoactivation of multiple therapeutic processes for enhanced efficacy. These include sequential activation of endosomal escape through photochemical-internalization for enhanced cellular uptake, followed by photocontrolled gene knockdown of superoxide dismutase-1 to increase sensitivity to reactive oxygen species and finally, photodynamic therapy under these favorable conditions. Such programmed activation translated to significantly higher therapeutic efficacy in vitro and in vivo in comparison to conventional, non-programmed activation.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Processos Fotoquímicos/efeitos da radiação , Animais , Compostos de Cálcio/química , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/efeitos da radiação , Desenho de Fármacos , Endossomos/efeitos dos fármacos , Técnicas de Inativação de Genes , Células HeLa , Humanos , Indóis/administração & dosagem , Indóis/farmacocinética , Raios Infravermelhos , Camundongos , Nanopartículas/efeitos da radiação , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Silicatos/química , Superóxido Dismutase-1/genética , Distribuição Tecidual , Raios Ultravioleta
7.
Oncol Rep ; 42(6): 2512-2520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545500

RESUMO

A novel core­shell type thermo­nanoparticle (CSTNP) co­loaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed IT­CSTNPs) was designed and combined with a near­infrared (NIR) laser to realize its photothermal conversion. The IT­CSTNPs were prepared using a two­step synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the IT­CSTNPs was 196.4±3.1 nm with a ζ potential of ­24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the IT­CSTNPs exhibited the desired photothermal conversion efficiency. The in vitro drug release curves revealed a suitable release capability of IT­CSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of IT­CSTNPs by A375 melanoma cells occurred in a concentration­dependent manner. Confocal laser scanning microscopy results indicated that IT­CSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of IT­CSTNPs.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Portadores de Fármacos/química , Hipertermia Induzida/métodos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Temozolomida/administração & dosagem , Antineoplásicos Alquilantes/farmacocinética , Linhagem Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos/efeitos da radiação , Difusão Dinâmica da Luz , Endocitose/efeitos da radiação , Humanos , Hipertermia Induzida/instrumentação , Verde de Indocianina/administração & dosagem , Verde de Indocianina/análogos & derivados , Lasers , Melanoma/patologia , Nanopartículas/química , Nanopartículas/efeitos da radiação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Neoplasias Cutâneas/patologia , Temozolomida/farmacocinética
8.
J Agric Food Chem ; 67(36): 9989-9999, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31430135

RESUMO

Zein's prevalent hydrophobic character is one of the major challenges associated with ineffective utilization as an aqueous nanocarrier for pesticides. Herein, we report an effective approach to hydrophilic modification of zein by phosphorylation using nontoxic sodium tripolyphosphate (STP), thereby improving the water-solubility, foliage wettability, and adhesion ability of zein as a nanocarrier for sustained release of pesticides. The procedure relied on zein grafted with STP via N- and O- phosphate bonds and encapsulation of avermectin (AVM) as a hydrophobic model drug using phosphorylated zein (P-Zein), which achieved pH sensitivity to controlled release of AVM in various applicable environments. The chemical interaction between zein and STP was confirmed by Fourier transform infrared, thermogravimetric analysis, and differential scanning calorimetric. Scanning electron microscopy, dynamic light scattering, and zeta potential technique were applied to investigate their structural characteristics and stability, from which it was found that AVM encapsulated in P-Zein (AVM@P-Zein) formed uniform nanoparticles with average sizes in the range of 174-278 nm under different conditions, and had an excellent stability in aqueous solution. Besides, AVM@P-Zein facilitated the wettability on the foliage surface evidenced from contact angle values owing to the amphiphilic character after phosphorylation as well as enhanced the adhesion ability between liquid and leaf, restricting the pesticide runoff. Ultraviolet-visible spectroscopy was employed to explore the anti-UV property and encapsulation as well as release behavior, which revealed that the presence of P-Zein like a shell protects AVM from UV photolysis with encapsulation efficiency of approximately 81.52%, and the release of AVM from P-Zein showed pH-responsive behavior ascribed to protonation and deprotonation of phosphate under various pH conditions fitting to Elovich kinetic model, achieving the relatively more rapid release under acidic conditions. More importantly, AVM@P-Zein retained the toxicity for insecticidal effect.


Assuntos
Preparações de Ação Retardada/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Inseticidas/química , Ivermectina/análogos & derivados , Nanopartículas/química , Zeína/química , Animais , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/efeitos da radiação , Composição de Medicamentos/instrumentação , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Inseticidas/farmacologia , Ivermectina/química , Ivermectina/farmacologia , Cinética , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Nanopartículas/efeitos da radiação , Fosforilação , Polifosfatos/química , Raios Ultravioleta , Zeína/efeitos da radiação
9.
Colloids Surf B Biointerfaces ; 183: 110423, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437608

RESUMO

Photothermal therapy (PTT) is a promising method to kill bacteria because of the broad-spectrum of antibacterial activity and the ability of spatiotemporal regulation. In the previously reported systems, light induced high temperature (˜70 °C) was essential for effectively killing of bacteria, which, however, would also damage nearby nontarget cells or tissues. Here we report photothermal nanoparticles (NPs) for more targeting and killing bacteria at a relative low temperature. Polydopamine (PDA) was chosen to prepare NPs because of its excellent capability of photothermal conversion. Magainin I (MagI) which is an antimicrobial peptide was used to modify NPs' surface because it can specifically interact with bacteria. We demonstrate that MagI-PEG@PDA NPs effectively killed E. coli at a low temperature of ˜45 °C upon near-infrared (NIR) light irradiation. In contrast, the native PDA NPs under light irradiation or the MagI-PEG@PDA NPs themselves showed no bacteria killing ability. This work highlights the importance of close interaction between the target bacteria and the photothermal materials and may promote the practical clinical applications of the PTT.


Assuntos
Antibacterianos/efeitos da radiação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Indóis/efeitos da radiação , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/efeitos da radiação , Polímeros/efeitos da radiação , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Escherichia coli/imunologia , Indóis/química , Raios Infravermelhos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos da radiação , Células NIH 3T3 , Nanopartículas/química , Nanopartículas/toxicidade , Polietilenoglicóis/química , Polímeros/química , Temperatura
10.
Colloids Surf B Biointerfaces ; 183: 110371, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408783

RESUMO

The abuse of antibiotics has led to widespread antimicrobial resistance (AMR) and environmental pollution. In order to solve these problems, a lot of studies have been carried out mainly focusing on the modification and recombination of organic reagents, but bacteria are still easy to adapt to it, so they cannot be thoroughly solved. Here, we present an integrated pollution-free synergistic antibacterial nanotechnology using inorganic nano-Cu2O, which could not only enhance the efficacy of aminoglycoside antibiotics, but also eliminate their environmental pollution by photocatalytic degradation. It was found that Cu2O showed significantly synergistic antibacterial effect (1+1>2) when combined with aminoglycoside antibiotics against Escherichia coli. The inhibition zone area increased by 59.0% when Cu2O combined with neomycin. This reduces dosage and the risk of AMR, and does not pollute the environment after degradation. Next, to explore the synergistic mechanisms, we have studied the interaction of antibiotics with nanoparticles, as well as the interaction of antibacterial agents with bacteria. At last, we believe that the destruction of cell walls by Cu2O facilitates the entry of antibiotics into cells is the reason for their synergy.


Assuntos
Antibacterianos/farmacologia , Cobre/farmacologia , Escherichia coli/efeitos dos fármacos , Nanopartículas/química , Neomicina/farmacologia , Antibacterianos/química , Antibacterianos/efeitos da radiação , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Cobre/química , Cobre/efeitos da radiação , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Luz , Testes de Sensibilidade Microbiana , Nanopartículas/efeitos da radiação , Nanopartículas/ultraestrutura , Nanotecnologia/métodos , Neomicina/química , Neomicina/efeitos da radiação , Fotólise
11.
Colloids Surf B Biointerfaces ; 182: 110393, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357128

RESUMO

In this work, photo-sensitive core/shell nanoparticles (NPs) based on biocompatible dextran-g-poly(o-nitrobenzyl acrylate) copolymers (Dex-g-PNBA), containing dextran as hydrophilic backbone and PNBA as photosensitive grafts, were formulated using two processes. In the first process (nanoprecipitation), NPs were prepared using preformed Dex-g-PNBA copolymers. Using the second process (emulsion/organic solvent evaporation), "clicked" or "unclicked" NPs were obtained carrying out (or not) an interfacial in situ click chemistry, respectively. Two model molecules, Nile Red (NR) and Doxorubicin (DOX), were encapsulated and their controlled release from NPs was investigated under UV irradiations to demonstrate the high potential of such photosensitive NPs in biomedicine applications as drug delivery nanocarriers. According to such irradiations, improved release was easily observed. Release kinetics depended on the formulation process and the NPs core chemistry, but not on the occurrence of the interfacial in situ click chemistry. More interesting, a stepped release of such model molecules may easily be obtained.


Assuntos
Acrilatos/química , Preparações de Ação Retardada/farmacologia , Dextranos/química , Doxorrubicina/farmacologia , Nanopartículas/química , Polímeros/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Química Click , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/efeitos da radiação , Raios Ultravioleta
12.
ACS Appl Mater Interfaces ; 11(30): 26581-26589, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31287647

RESUMO

Herein, we developed a nanocomposite membrane with synergistic photodynamic therapy and photothermal therapy antibacterial effects, triggered by a single near-infrared (NIR) light illumination. First, upconversion nanoparticles (UCNPs) with a hierarchical structure (UCNPs@TiO2) were synthesized, which use NaYF4:Yb,Tm nanorods as the core and TiO2 nanoparticles as the outer shell. Then, nanosized graphene oxide (GO), as a photothermal agent, was doped into UCNPs@TiO2 core-shell nanoparticles to obtain UCNPs@TiO2@GO. Afterward, the mixture of UCNPs@TiO2@GO in poly(vinylidene) fluoride (PVDF) was applied for electrospinning to generate the nanocomposite membrane (UTG-PVDF). Generation of reactive oxygen species (ROS) and changes of temperature triggered by NIR action were both investigated to evaluate the photodynamic and photothermal properties. Upon a single NIR light (980 nm) irradiation for 5 min, the nanocomposite membrane could simultaneously generate ROS and moderate temperature rise, triggering synergistic antibacterial effects against both Gram-positive and -negative bacteria, which are hard to be achieved by an individual photodynamic or photothermal nanocomposite membrane. Additionally, the as-prepared membrane can effectively restrain the inflammatory reaction and accelerate wound healing, thus exhibiting great potentials in treating infectious complications in wound healing progress.


Assuntos
Antibacterianos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fotoquimioterapia , Antibacterianos/farmacologia , Antibacterianos/efeitos da radiação , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Grafite/química , Grafite/farmacologia , Humanos , Raios Infravermelhos , Nanocompostos/química , Nanocompostos/efeitos da radiação , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/uso terapêutico , Nanotubos/química , Nanotubos/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Polivinil/química , Polivinil/uso terapêutico , Espécies Reativas de Oxigênio/química , Titânio/química , Titânio/farmacologia
13.
Photobiomodul Photomed Laser Surg ; 37(10): 596-605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31335302

RESUMO

Brain photobiomodulation (PBM) describes the use of visible to near-infrared light for modulation or stimulation of the central nervous system in both healthy individuals and diseased conditions. Although the transcranial approach to delivering light to the head is the most common technique to stimulate the brain, delivery of light to deeper structures in the brain is still a challenge. The science of nanoparticle engineering in combination with biophotonic excitation could provide a way to overcome this problem. Upconversion is an anti-Stokes process that is capable of transforming low energy photons that penetrate tissue well to higher energy photons with a greater biological effect, but poor tissue penetration. Wavelengths in the third optical window are optimal for light penetration into brain tissue, followed by windows II, IV, and I. The combination of trivalent lanthanide ions within a crystalline host provides a nanostructure that exhibits the upconversion phenomenon. Upconverting nanoparticles (UCNPs) have been successfully used in various medical fields. Their ability to cross the brain-blood barrier and their low toxicity make them a good candidate for application in brain disorders. It is possible that delivery of UCNPs to the brainstem or deeper parts of the cerebral tissue, followed by irradiation using light wavelengths with good tissue penetration properties, could allow more efficient PBM of the brain.


Assuntos
Encéfalo/efeitos da radiação , Elementos da Série dos Lantanídeos/química , Terapia com Luz de Baixa Intensidade/métodos , Nanopartículas/efeitos da radiação , Animais , Encéfalo/metabolismo , Feminino , Humanos , Elementos da Série dos Lantanídeos/efeitos da radiação , Masculino , Nanopartículas/química , Sensibilidade e Especificidade
14.
Nat Commun ; 10(1): 3089, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300649

RESUMO

Dual-emissive systems showing color-specific photoswitching are promising in bioimaging and super-resolution microscopy. However, their switching efficiency has been limited because a delicate manipulation of all the energy transfer crosstalks in the systems is unfeasible. Here, we report a perfect color-specific photoswitching, which is rationally designed by combining the complete off-to-on fluorescence switching capability of a fluorescent photochromic diarylethene and the frustrated energy transfer to the other fluorescent dye based on the excited-state intramolecular proton transfer (ESIPT) process. Upon alternation of UV and visible light irradiations, the system achieves 100% switching on/off of blue emission from the diarylethene while orange emission from the ESIPT dye is unchanged in the polymer film. By fabricating this system into biocompatible polymer nanoparticles, we demonstrate microscopic imaging of RAW264.7 macrophage cells with reversible blue-color specific fluorescence switching that enables super-resolution imaging with a resolution of 70 nm.


Assuntos
Transferência de Energia/efeitos da radiação , Corantes Fluorescentes/química , Microscopia Intravital/métodos , Imagem Molecular/métodos , Nanopartículas/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/efeitos da radiação , Cor , Fluorescência , Corantes Fluorescentes/efeitos da radiação , Luz , Camundongos , Microscopia Eletrônica de Transmissão/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Células RAW 264.7
15.
Nat Commun ; 10(1): 2839, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253798

RESUMO

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.


Assuntos
Raios Infravermelhos , Nanopartículas/efeitos da radiação , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Feminino , Imunomodulação , Macrófagos , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Raios Ultravioleta
16.
Int J Pharm ; 566: 549-556, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158452

RESUMO

The near-infrared dye, IR780 iodide, has been utilized in photodynamic therapy (PDT) and photothermal therapy (PTT). However, the hydrophobicity and photosensitivity of IR780 limit its further applications in biomedical fields. Herein, the hydrophilic sericin was modified with hydrophobic cholesterol to form an amphiphilic macromolecular conjugate (Ser-Chol). The tumor-targeting agent, folic acid (FA), was further linked to the conjugate (FA-Ser-Chol). The IR780 could be encapsulated into such amphiphilic macromolecule to form stable micelles (FA-Ser-Chol/IR780) by self-assembly, and the solubility and photo-stability of IR780 were greatly improved. The FA-Ser-Chol/IR780 micelles could be efficiently absorbed by FA-positive gastric cancer cells (BGC-823) through FA receptors, while the uptake micelles showed remarkable PDT and PTT cytotoxicity towards BGC-823 cells under laser irradiation of 808 nm. Therefore, FA-Ser-Chol micelles may serve as a promising IR780 carrier for PDT and PTT therapy.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Micelas , Nanopartículas/administração & dosagem , Fototerapia , Sericinas/administração & dosagem , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Portadores de Fármacos/efeitos da radiação , Ácido Fólico/administração & dosagem , Humanos , Indóis/administração & dosagem , Lasers , Nanopartículas/efeitos da radiação , Sericinas/efeitos da radiação , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
17.
Biomolecules ; 9(5)2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137744

RESUMO

In this review, we intend to highlight the progress which has been made in recent years around different types of smart activation nanosystems for cancer treatment. Conventional treatment methods, such as chemotherapy or radiotherapy, suffer from a lack of specific targeting and consequent off-target effects. This has led to the development of smart nanosystems which can effect specific regional and temporal activation. In this review, we will discuss the different methodologies which have been designed to permit activation at the tumour site. These can be divided into mechanisms which take advantage of the differences between healthy cells and cancer cells to trigger activation, and those which activate by a mechanism extrinsic to the cell or tumour environment.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Humanos , Nanopartículas/metabolismo , Nanopartículas/efeitos da radiação , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Polímeros Responsivos a Estímulos/química
18.
Phys Med Biol ; 64(12): 125018, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31071701

RESUMO

Nanoparticle-mediated histotripsy (NMH) is an ultrasound treatment strategy that combines acoustically sensitive nanoparticles with histotripsy. Previous NMH studies using perfluorocarbon (PFC) nanodroplets (ND's), ~200 nm in diameter, demonstrated that NMH can selectively generate cavitation by reducing the cavitation threshold from ~25-30 MPa to ~10-15 MPa. Recent studies have also shown that cavitation nucleation in NMH is directly caused by the incident negative pressure (p-) exposed to the PFC, as predicted by classical nucleation theory (CNT), suggesting that the NMH cavitation threshold is dependent on the total volume of PFC present in the focal region. In this study, we investigate the use of a newly developed NMH nanoparticle synthesized using an inclusion complex of methylated ß-cyclodextrin and perfluorohexane (PFH). These 'nanocones' (NCs) have advantages compared to previously used ND's due to their smaller size (~50 nm), simple synthesis method, higher stability and information of definite PFH amount carried by the NC. To test the hypothesis that NCs can reduce the NMH cavitation threshold similar to ND's, and that the NMH cavitation threshold is dependent upon the total PFH concentration, tissue phantoms containing concentrations of NCs ranging from 10-5 to 10-10 (ml PFH/ml water) were exposed to single cycle ultrasound pulses using a 500 kHz focused transducer where high speed imaging captured cavitation data. Results showed that NCs significantly reduced the histotripsy cavitation threshold to 11.0 MPa for a concentration of 10-5 (ml PFH/ml water), with the threshold increasing at lower concentrations. Finally, the ability of NCs to be used for effective NMH ablation was demonstrated in tissue phantoms containing red blood cells (RBCs). Overall, the results of the study support our hypotheses that NCs can be used for effective NMH therapy and that NC concentration has a predictable threshold-reducing effect.


Assuntos
Eritrócitos/efeitos da radiação , Fluorcarbonetos/química , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Litotripsia/instrumentação , Nanopartículas/efeitos da radiação , Imagens de Fantasmas , Humanos
19.
Talanta ; 201: 126-133, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122402

RESUMO

Upconversion nanoparticle-based lateral flow assays (UCNP-LFAs) have attracted significant attention in point-of-care testing (POCT) applications, due to the long-term photostability and enhanced signal-to-background noise ratio. The existing UCNP-LFAs generally require peripheral equipment for exciting fluorescent signals and reading out fluorescence results, which are generally bulky and expensive. Herein, we developed a miniaturized and portable UCNP-LFA platform, which is composed of a LFA detection system, an UCNP-LFA reader and a smartphone-assisted UCNP-LFA analyzer. The LFA detection system is based on three types of UCNPs for multiplexed detection. The reader has a dimension of 24.0 cm × 9.4 cm × 5.4 cm (L × W × H) and weight of 0.9 kg. The analyzer based on the custom-designed software of a smartphone (termed as UCNP-LFA analyzer) can get the quantitative analysis results in a real-time manner. We demonstrated the universality of this platform by highly sensitive and quantitative detections of several kinds of targets, including small molecule (ochratoxin A, OTA), heavy metal ion (Hg2+), bacteria (salmonella, SE), nucleic acid (hepatitis B virus, HBV) and protein (growth stimulation expressed gene 2, ST-2). Our developed UCNP-LFA platform holds great promise for applications in disease diagnostics, environmental pollution monitoring and food safety at the point of care.


Assuntos
Imunoensaio/métodos , Nanopartículas/química , Testes Imediatos , Anticorpos/química , Biomarcadores/sangue , DNA/análise , DNA/química , DNA/genética , Érbio/química , Fluoretos/química , Fluoretos/efeitos da radiação , Vírus da Hepatite B/genética , Humanos , Imunoensaio/instrumentação , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Limite de Detecção , Mercúrio/análise , Nanopartículas/efeitos da radiação , Hibridização de Ácido Nucleico , Salmonella/isolamento & purificação , Smartphone , Espectrometria de Fluorescência/métodos , Itérbio/química , Ítrio/química , Ítrio/efeitos da radiação
20.
Int J Pharm ; 565: 199-208, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31051231

RESUMO

Nanoparticles (NP) have gained importance as drug delivery systems for pharmaceutical challenging drugs. Their size properties allow passive targeting of cancer tissue by exploiting the enhanced permeability and retention (EPR) effect. Furthermore, surface modifications enable an active drug targeting for diseased regions in the human body. Besides the advantages, the drug release from commonly used biodegradable NP is mostly depending on physiological circumstances. Hence, there is a need for a more controllable drug release. The use of light-responsive polymers is an innovative conception enabling a more distinct drug release by an external light stimulus. The idea provides potential for an increase in efficiency and safety of local therapies. In this study, innovative light-sensitive NP were investigated for a photodynamic therapy (PDT) of gastrointestinal tumors. Nanoparticles based on a newly developed light-responsive polycarbonate (LrPC) and poly(lactic-co-glycolic-acid) (PLGA) were loaded with the approved photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). Mucus penetrating properties were obtained by surface PEGylation of the nanoparticles either by using LrPC in combination with a PEGylated PLA (PEG-PLA) or by a combination with PEGylated LrPC (LrPC-PEG). Cytotoxic potential in dependency of a light-induced drug release was investigated in different cytotoxicity assays. Intracellular accumulation in mucus producing colon-carcinoma cell line HT-29-MTX was analysed by HPLC and confocal laser microscopy.


Assuntos
Neoplasias Intestinais/tratamento farmacológico , Mesoporfirinas , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/efeitos da radiação , Células HT29 , Humanos , Luz , Mesoporfirinas/administração & dosagem , Mesoporfirinas/química , Mesoporfirinas/efeitos da radiação , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/administração & dosagem , Polímeros/química , Polímeros/efeitos da radiação
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