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1.
Biomaterials ; 255: 120202, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32562941

RESUMO

Overexpression of P-glycoprotein (P-gp), which is responsible for pumping chemotherapeutic drugs out of tumor cells, has been recognized as an important cause of drug resistance in conventional chemotherapy. Herein, porous platinum nanoparticles (pPt NPs) are developed to enable the combined electrodynamic therapy (EDT) with chemotherapy. With polyethylene glycol (PEG) coating, the obtained pPt-PEG NPs could be loaded with anticancer drug doxorubicin (DOX) by utilizing the porous structure of pPt NPs. Those pPt-PEG NPs are able to produce reactive oxygen species (ROS) by triggering water decomposition under electric field, independent of O2 and H2O2 contents in the tumor. Furthermore, the ROS generated during EDT could induce the inhibition of P-glycoprotein (P-gp), in turn enhancing the efficacy of chemotherapeutic agents by facilitating intracellular accumulation of drugs. As the results, excellent synergetic therapeutic effects were observed by combining chemotherapy with EDT using DOX-loaded pPt (DOX@pPt-PEG) NPs, as demonstrated by both in vitro and in vivo experiments. This study demonstrates a new concept of combinational cancer therapy with superior therapeutic efficacy.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Linhagem Celular Tumoral , Doxorrubicina , Peróxido de Hidrogênio , Platina , Porosidade
2.
Chem Commun (Camb) ; 55(62): 9104-9107, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31298232

RESUMO

We have developed a photoluminescent membrane for microRNA detection, consisting of chemically modified mesoporous silica nanoparticles (CaF2:Yb/Ho@MSNs) attached, via single stranded DNA probes, to flexible polyurethane fibres coated with graphene oxide (GO). By detecting the release of the luminescent nanoparticles resulting from complementary co-hybridization between target miRNA sequences and the DNA probe, accurate measurements of the miRNA concentration at high sensitivity levels can be obtained. The constructs therefore offer a route to rapid detection and the potential for early cancer diagnosis.


Assuntos
Técnicas Biossensoriais , Grafite/química , MicroRNAs/análise , Nanopartículas/química , Dióxido de Silício/química , Tamanho da Partícula , Porosidade , Propriedades de Superfície
3.
Adv Mater ; 31(14): e1806803, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734370

RESUMO

Electrochemical therapy (EChT), by inserting electrodes directly into tumors to kill cancer cells under direct current (DC), is clinically used in several countries. In EChT, the drastic pH variation nearby the inserted electrodes is the main cause of tumor damage. However, its limited effective area and complex electrode configuration have hindered the clinical application of EChT in treating diverse tumor types. Herein, a conceptually new electric cancer treatment approach is presented through an electro-driven catalytic reaction with platinum nanoparticles (PtNPs) under a square-wave alternating current (AC). The electric current triggers a reaction between water molecules and chloride ions on the surface of the PtNPs, generating cytotoxic hydroxyl radicals. Such a mechanism, called electrodynamic therapy (EDT), enables effective killing of cancer cells within the whole electric field, in contrast to EChT, which is limited to areas nearby electrodes. Remarkable tumor destruction efficacy is further demonstrated in this in vivo EDT treatment with PtNPs. Therefore, this study presents a new type of cancer therapy strategy with a tumor-killing mechanism different from existing methods, using nanoparticles with electrocatalytic functions. This EDT method appears to be minimally invasive, and is able to offer homogeneous killing effects to the entire tumor with a relatively large size.


Assuntos
Terapia por Estimulação Elétrica/métodos , Nanopartículas Metálicas/química , Platina/química , Platina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia por Estimulação Elétrica/instrumentação , Eletroquímica , Eletrodos , Humanos , Modelos Moleculares , Conformação Molecular , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
4.
ACS Appl Mater Interfaces ; 10(18): 15494-15503, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29682957

RESUMO

The efficacy of the conventional photodynamic therapy (PDT) is markedly suppressed by limited penetration depth of light in biological tissues and oxygen depletion in the hypoxic tumor microenvironment. Herein, mesoporous silica nanospheres with fine CaF2:Yb,Er upconversion nanocrystals entrapped in their porous structure are synthesized via a thermal decomposition method. After subsequently coating with a thin MnO2 layer and loading with a photosensitizer, Chlorin e6 (Ce6), a new type of nanoscale PDT platform is obtained. Within such composite nanoparticles, Mn2+ ions doped into the lattice of CaF2 crystals effectively enhance the near-infrared (NIR)-triggered red-light upconversion photoluminescence for exciting the adsorbed Ce6 via resonance energy transfer, enabling the improved photodynamic phenomenon. Meanwhile, the MnO2 coating modulates the hypoxic tumor microenvironment by in situ generating O2 through the reaction with tumor endogenous H2O2. Both mechanisms acting synchronously lead to the superior therapeutic outcome in NIR-triggered photodynamic tumor therapy.


Assuntos
Nanopartículas , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Raios Infravermelhos , Fotoquimioterapia , Hipóxia Tumoral
5.
J Mater Chem B ; 5(34): 7133-7139, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32263904

RESUMO

MicroRNAs (miRNAs) play a key role in regulating gene expression but can be associated with abnormalities linked to carcinogenesis and tumor progression. Hence there is increasing interest in developing methods to detect these non-coding RNA molecules in the human circulation system. Here, a novel FRET miRNA-195 targeting biosensor, based on silica nanofibers incorporated with rare earth-doped calcium fluoride particles (CaF2:Yb,Ho@SiO2) and gold nanoparticles (AuNPs), is reported. The formation of a sandwich structure, as a result of co-hybridization of the target miRNA which is captured by oligonucleotides conjugated at the surface of CaF2:Yb,Ho@SiO2 fibers and AuNPs, brings the nanofibers and AuNPs in close proximity and triggers the FRET effect. The intensity ratio of green to red emission, I541/I650, was found to decrease linearly upon increasing the concentration of the target miRNA and this can be utilized as a standard curve for quantitative determination of miRNA concentration. This assay offers a simple and convenient method for miRNA quantification, with the potential for rapid and early clinical diagnosis of diseases such as breast cancer.

6.
Part Part Syst Charact ; 33(12): 896-905, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28670098

RESUMO

Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli-responsive drug delivery systems. Here, a nanoparticle system, CaF2:Tm,Yb@mSiO2, made of a mesoporous silica (mSiO2) nanosphere with CaF2:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF2:Tm,Yb@mSiO2 enables us to trigger the drug release by two mechanisms. One is the pH-triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)-triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual-triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.

7.
Curr Pharm Des ; 21(22): 3239-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26027562

RESUMO

Electrohydrodynamic atomization (EHDA) enabling platform technologies have gathered significant momentum over the last two decades. Utilisation of the underpinning jetting process in tandem with desired materials (including polymers, ceramics, metals and even naturally occurring compounds such as peptides, DNA and cells) provides the basis for novel engineered therapies. Through EHDA processes, the generation of a variety of nano-meter and micro-meter scaled structures with control on surface and encapsulation features is attainable in a single step. While a host of adaptable EHDA techniques have evolved (e.g. printing and template patterning), there are two main processes that continue to dominate: electrospraying (ESy) and electrospinning (ESp). Although ESp has drawn considerable researcher interest for nanofibre applications, ESy is an important and timely process for nano- and micro-particle fabrication. Thus, an appropriate evaluation of ESy is vital. This short review focuses on key developments in the ESy field in relation to nanotechnologies with potential healthcare applications using metals, polymers and ceramics. An insight into the process of particle formation (during EHDA spraying or ESy), process parameters and materials specifications, is provided. Emerging biomedical and other healthcare research through nanotechnologies are highlighted.


Assuntos
Nanotecnologia , Humanos , Metais/química , Nanomedicina/métodos , Nanopartículas/química , Nanotecnologia/métodos , Polímeros/química , Propriedades de Superfície
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