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OBJECTIVE: To propose a transfer learning based method of tumor segmentation in intraoperative fluorescence images, which will assist surgeons to efficiently and accurately identify the boundary of tumors of interest. METHODS: We employed transfer learning and deep convolutional neural networks (DCNNs) for tumor segmentation. Specifically, we first pre-trained four networks on the ImageNet dataset to extract low-level features. Subsequently, we fine-tuned these networks on two fluorescence image datasets (ABFM and DTHP) separately to enhance the segmentation performance of fluorescence images. Finally, we tested the trained models on the DTHL dataset. The performance of this approach was compared and evaluated against DCNNs trained end-to-end and the traditional level-set method. RESULTS: The transfer learning-based UNet++ model achieved high segmentation accuracies of 82.17% on the ABFM dataset, 95.61% on the DTHP dataset, and 85.49% on the DTHL test set. For the DTHP dataset, the pre-trained Deeplab v3 + network performed exceptionally well, with a segmentation accuracy of 96.48%. Furthermore, all models achieved segmentation accuracies of over 90% when dealing with the DTHP dataset. CONCLUSION: To the best of our knowledge, this study explores tumor segmentation on intraoperative fluorescent images for the first time. The results show that compared to traditional methods, deep learning has significant advantages in improving segmentation performance. Transfer learning enables deep learning models to perform better on small-sample fluorescence image data compared to end-to-end training. This discovery provides strong support for surgeons to obtain more reliable and accurate image segmentation results during surgery.
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Redes Neurais de Computação , Imagem Óptica , Humanos , Imagem Óptica/métodos , Neoplasias/cirurgia , Neoplasias/diagnóstico por imagem , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Cirurgia Assistida por Computador/métodosRESUMO
Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a ß-cyclodextrin-modified cb-apt (cb-apt-ßCD) and its supramolecular interaction with molecular therapeutics via host-guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer. The cb-apt-ßCD ensemble delivers green fluorescent protein into targeted cells with efficiency as high as 80%, or cytotoxic saporin to efficiently inhibit tumor cell growth. The strategy of conjugating ßCD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-ßCD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.
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Aptâmeros de Nucleotídeos/química , Sistemas de Liberação de Medicamentos , Proteínas de Fluorescência Verde/metabolismo , Proteínas Inativadoras de Ribossomos Tipo 1/metabolismo , beta-Ciclodextrinas/química , Aptâmeros de Nucleotídeos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Fluorescência Verde/química , Células HeLa , Humanos , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Proteínas Inativadoras de Ribossomos Tipo 1/química , Saporinas , beta-Ciclodextrinas/farmacologiaRESUMO
Enhanced targeted gene transduction by AAV2 vectors is achieved by linking the vector to multiple sgc8 aptamers, which are selective for cell membrane protein PTK7. Aptamer molecules are conjugated to multiple sites on a DNA dendrimer (G-sgc8), which is then linked to AAV2 via a dithiobis(succinimidyl propionate) cross-linker containing a disulfide group, which can facilitate the release of AAV2 vectors by reaction with the reduced form of intracellular glutathione. The G-sgc8-AAV2 vectors showed a 21-fold enhancement in binding affinity and an enhanced ability to protect sgc8 aptamers against nuclease degradation to cells expressing PTK7 compared to single aptamer-AAV2 conjugates. The transduction efficiency was tested by loading AAV2 with the gene for green fluorescent protein. Therefore, this modified recombinant vector is an attractive and promising tool for targeted biomedical applications.
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Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Dissulfetos/química , Vetores Genéticos/química , Vetores Genéticos/genética , Transdução Genética/métodos , Vírus/genética , Linhagem Celular Tumoral , DNA de Neoplasias/química , Dendrímeros/síntese química , Dendrímeros/química , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Oxirredução , Vírus/químicaRESUMO
OBJECTIVE: Our aim was to evaluate the effect of aquatic obstacle training on balance parameters in comparison with a traditional aquatic therapy in patients with Parkinson's disease. DESIGN: A randomized single-blind controlled trial. SETTING: Outpatients in the rehabilitation department. SUBJECTS: A total of 46 patients with Parkinson's disease in Hoehn-Yahr stage 2-3. INTERVENTIONS: Participants were randomly assigned to (1) aquatic therapy or (2) obstacle aquatic therapy. All participants undertook aquatic therapy for 30 minutes, five times per week for six weeks. MAIN MEASURES: The Freezing of Gait Questionnaire, Functional Reach Test, Timed Up and Go test and Berg Balance Scale were assessed at baseline, posttreatment and at six-month follow-up. RESULTS: Both groups of patients had improved primary outcomes after the training program. A between-group comparison of the changes revealed that obstacle aquatic therapy was significantly higher for the Freezing of Gait Questionnaire (after treatment: 8.7 ± 3.3 vs 6.2 ± 2.1, P = 0.004; posttest: 7.7 ± 3.1 vs 5.3 ± 2.0, P = 0.003) and Timed Up and Go test (after treatment: 17.1 ± 2.9 vs 13.8 ± 1.9, P < 0.001; posttest: 16.3 ± 2.8 vs 12.9 ± 1.4, P < 0.001). CONCLUSION: Obstacle aquatic therapy in this protocol seems to be more effective than traditional protocols for gait and balance in patients with Parkinson's disease, and the effect lasts for six months.
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Terapia por Exercício , Marcha/fisiologia , Doença de Parkinson/reabilitação , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Estudos Prospectivos , Método Simples-Cego , Resultado do TratamentoRESUMO
Photoresponsive materials are emerging as ideal carriers for precisely controlled drug delivery owing to their high spatiotemporal selectivity. However, drawbacks such as slow release kinetics, inherent toxicity, and lack of targeting ability hinder their translation into clinical use. We constructed a new DNA aptamer-grafted photoresponsive hyperbranched polymer, which can self-assemble into nanoparticles, thereby achieving biocompatibility and target specificity, as well as light-controllable release behavior. Upon UV-irradiation, rapid release induced by disassembly was observed for Nile Red-loaded nanoparticles. Further inâ vitro cell studies confirmed this delivery system's specific binding and internalization performance arising from the DNA aptamer corona. The DOX-loaded nanoassembly exhibited selective phototriggered cytotoxicity towards cancer cells, indicating its promising therapeutic effect as a smart drug delivery system.
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Antibióticos Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Polímeros/química , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Processos Fotoquímicos , Polímeros/síntese química , Espectrometria de Fluorescência , Raios UltravioletaRESUMO
The specific binding ability of DNA-lipid micelles (DLMs) can be increased by the introduction of an aptamer. However, supramolecular micellar structures based on self-assemblies of amphiphilic DLMs are expected to demonstrate low stability when interacting with cell membranes under certain conditions, which could lead to a reduction in selectivity for targeting cancer cells. We herein report a straightforward cross-linking strategy that relies on a methacrylamide branch to link aptamer and lipid segments. By an efficient photoinduced polymerization process, covalently linked aptamer-lipid units help stabilize the micelle structure and enhance aptamer probe stability, further improving the targeting ability of the resulting nanoassembly. Besides the development of a facile cross-linking method, this study clarifies the relationship between aptamer-lipid concentration and the corresponding binding ability.
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Acrilamidas/química , Aptâmeros de Nucleotídeos/química , Reagentes de Ligações Cruzadas/química , Portadores de Fármacos/química , Lipídeos/química , Micelas , Linhagem Celular , Sistemas de Liberação de Medicamentos , Humanos , PolimerizaçãoRESUMO
Site-selective protein modification is a key step in facilitating protein functionalization and manipulation. To accomplish this, genetically engineered proteins were previously required, but the procedure was laborious, complex, and technically challenging. Herein we report the development of aptamer-based recognition-then-reaction to guide site-selective protein/DNA conjugation in a single step with outstanding selectivity and efficiency. As models, several proteins, including human thrombin, PDGF-BB, Avidin, and His-tagged recombinant protein, were studied, and the results showed excellent selectivity under mild reaction conditions. Taking advantage of aptamers as recognition elements with extraordinary selectivity and affinity, this simple preparation method can tag a protein in a complex milieu. Thus, with the aptamer obtained from cell-SELEX, real-time modification of live-cell membrane proteins can be achieved in one step without any pre-treatment.
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Proteínas/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Membrana Celular/metabolismo , Humanos , Técnica de Seleção de Aptâmeros , Trombina/metabolismoRESUMO
Laboratory inâ vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypicanâ 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six-letter genetic alphabet containing the standard nucleobases and two added nucleobases (2-amino-8H-imidazo[1,2-a][1,3,5]triazin-4-one and 6-amino-5-nitropyridin-2-one), Watson-Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against non-engineered cells, eight AEGIS-containing aptamers were recovered. Five bound selectively to GPC3-overexpressing cells. This selection-counterselection scheme had acceptable statistics, notwithstanding the possibility that cells engineered to overexpress GPC3 might also express different off-target proteins. This is the first example of such a combination.
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Aptâmeros de Nucleotídeos/metabolismo , Glipicanas/metabolismo , Animais , Aptâmeros de Nucleotídeos/química , Sequência de Bases , Engenharia Celular , Linhagem Celular , Técnicas de Laboratório Clínico , Citometria de Fluxo , Glipicanas/química , Glipicanas/genética , Humanos , Camundongos , Ligação ProteicaRESUMO
A facile strategy has been developed to fabricate Cu(OH)2 supercages (SCs) as an artificial enzyme system with intrinsic peroxidase-mimic activities (PMA). SCs with high catalytic activity and excellent recyclability were generated via direct conversion of amorphous Cu(OH)2 nanoparticles (NPs) at room temperature. More specifically, the process that takes a single nanoparticle to a 3D supercage involves two basic steps. First, with addition of a copper-ammonia complex, the Cu(2+) ions that are located on the surface of amorphous Cu(OH)2 NPs would evolve into a fine lamellar structure by coordination and migration and eventually convert to 1D nanoribbons around the NPs. Second, accompanied by the migration of Cu(2+), a hollow cavity is generated in the inner NPs, such that a single nanoparticle eventually becomes a nanoribbon-assembled 3D hollow cage. These Cu(OH)2 SCs were then engineered as an artificial enzymatic system with higher efficiency for intrinsic PMA than the peroxidase activity of a natural enzyme, horseradish peroxidase.
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Cobre/química , Hidróxidos/química , Nanopartículas/química , Catálise , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Inorganic colloidal nanoparticles (NPs) stabilized by a layer of hydrophobic surfactant on their surfaces have poor solubility in the aqueous phase, thus limiting their application as biosensors under physiological conditions. Here we report a simple model to ionize various types of hydrophobic colloidal NPs, including FePt, cubic Fe3O4, Pd, CdSe, and NaYF4 (Yb 30%, Er 2%, Nd 1%) NPs, to multicharged (positive and negative) NPs via ligand exchange. Surfaces of neutral hydrophobic NPs were converted to multicharged ions, thus making them soluble in water. Furthermore, peroxidase-like activity was observed for ionic FePt, Fe3O4, Pd, and CdSe NPs, of which FePt and CdSe catalyzed the oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) to the blue-colored product in the absence of H2O2, while Pd and Fe3O4 catalyzed the oxidization of TMB in the presence of H2O2. With the benefit of the ionic functionalization protocols described herein, colloidal NPs should gain wider use as biomarkers, nanozymes, and biosensors.
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Coloides/química , Enzimas/química , Nanopartículas/química , Interações Hidrofóbicas e Hidrofílicas , Íons , Microscopia Eletrônica de Transmissão , Análise EspectralRESUMO
Here, we report the synthesis and characterization of size-controllable and stimuli-responsive DNA nanohydrogels as effective targeted gene delivery vectors. DNA nanohydrogels were created through a self-assembly process using three kinds of building units, respectively termed Y-shaped monomer A with three sticky ends (YMA), Y-shaped monomer B with one sticky end (YMB), and DNA linker (LK) with two sticky ends. Hybridization at the sticky ends of monomers and LK leads to nanohydrogel formation. DNA nanohydrogels are size-controllable by varying the ratio of YMA to YMB. By incorporating different functional elements, such as aptamers, disulfide linkages, and therapeutic genes into different building units, the synthesized aptamer-based nanohydrogels (Y-gel-Apt) can be used for targeted and stimuli-responsive gene therapy. Y-gel-Apt strongly inhibited cell proliferation and migration in target A549 cells, but not in control cells. By taking advantage of facile modular design and assembly, efficient cellular uptake, and superior biocompatibility, this Y-gel-Apt holds great promise as a candidate for targeted gene or drug delivery and cancer therapy.
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Aptâmeros de Nucleotídeos/administração & dosagem , DNA/administração & dosagem , Preparações de Ação Retardada/química , Técnicas de Transferência de Genes , Hidrogéis/química , Nanopartículas/química , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , DNA/química , Dissulfetos/química , Células HeLa , Humanos , Nanopartículas/ultraestrutura , Tamanho da PartículaRESUMO
INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.
Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Equilíbrio Postural , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Masculino , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/diagnóstico , Idoso , Equilíbrio Postural/fisiologia , Pessoa de Meia-IdadeRESUMO
The objectives of this study were to analyze the distribution characteristics of frailty phenotypes in older adults of Chinese nursing homes, and to compare some motor function characteristics of older adults in nursing homes between frailty and non-frailty, to determine which motor function and frailty are related. This cross-sectional study included 177 older adults living in nursing homes. Frailty was diagnosed by Fried's phenotype, and motor function assessment characteristics (including muscle tone, ROM, and balance) were also evaluated. Chi-square and logistic regression analyses were performed. Frailty prevalence was 53% in nursing homes in big Chinese cities (average age 82.0â ±â 6.1). Low levels of physical activity (90.4% in frail elder), decreased handgrip strength (98.9% in frail elder) and slowed walking speed (100% in frail elder) were the 3 main components of the frailty phenotype of frail adults in nursing homes in China. It is worth noting that 74.7% of the non-frail elders also had reduced handgrip strength. Further analysis showed that balance (Pâ <â .001), muscle tone (upper, Pâ =â .028, lower, Pâ =â .001) and the range of motion (Pâ <â .001) were associated with frailty in older adults. The frailty of the elders in Chinese nursing homes was characterized by the decline of motor function. And surprisingly, both frail and non-frail elders were found to have poor strength. Frail nursing home seniors also have body muscle tone, range of motion and balance problems. The elderly of China should focus on strength, stretch and balance training to improve motor function, especially strength training, which is important for prevention frailty.
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Idoso Fragilizado , Fragilidade , Humanos , Idoso , Estudos Transversais , Força da Mão , Avaliação Geriátrica , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Casas de SaúdeRESUMO
Background: Early rehabilitation (ER) has been reported to be both safe and feasible for patients' post-stroke. To date, however, ER-related outcomes concerning patients who have undergone mechanical thrombectomy (MT) have not been investigated. This study aimed to determine the feasibility of ER and whether it improves prognosis in such patients. Methods: In this single-center, double-blinded, randomized controlled study involving 103 patients who met the study criteria (i.e., has undergone MT), we randomly divided patients (1:1) into ER and conventional rehabilitation groups. The primary outcome was mortality, while secondary outcomes included favorable outcomes (modified Rankin scale of 0-2), the incidence of non-fatal complications, and Barthel Index (BI) scores. We assessed outcomes at 3 months and 1-year post-stroke. Results: No significant between-group differences were found in terms of mortality and favorable outcomes at 3 months and 1-year post-stroke. At 3 months, 15 (28.8%) patients in the ER group and 29 (56.9%) in the conventional rehabilitation group (p = 0.002) had non-fatal complications. The BI in the ER and conventional rehabilitation groups was 100 (85-100) and 87.5 (60-100), respectively, (p = 0.007). At 1 year, the incidence of non-fatal complications was similar between both groups [BI in the ER group, 100 (90-100), p = 0.235; BI in the conventional rehabilitation group, 90 (63.8-100); p = 0.003]. Conclusion: Early rehabilitation (ER) reduces the incidence of early immobility-related complications and effectively improves patients' activities of daily living on a short- and long-term basis. Our results indicate that MT contributes to ER in patients with stroke. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900022665.
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Lipid nanoparticles (LNPs) are increasingly employed to improve delivery efficiency and therapeutic efficacy of nucleic acids. Various formulation parameters can affect the quality attributes of these nanoparticle formulations, but currently there is a lack of systemic screening approaches to address this challenge. Here, we developed an automated high-throughput screening (HTS) workflow for streamline preparation and analytical characterization of LNPs loaded with antisense oligonucleotides (ASOs) in a full 96-well plate within 3 hrs. ASO-loaded LNPs were formulated by an automated solvent-injection method using a robotic liquid handler, and assessed for particle size distribution, encapsulation efficiency, and stability with different formulation compositions and ASO loadings. Results indicated that the PEGylated lipid content significantly affected the particle size distribution, while the ionizable lipid / ASO charge ratio impacted the encapsulation efficiency of ASOs. Furthermore, results from our HTS approach correlated with those from the state-of-the-art scale-up method using a microfluidic formulator, therefore opening up a new avenue for robust formulation development and design of experiment methods, while reducing material usage by 10 folds, improving analytical outputs and accumulation of information by 100 folds.
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Nanopartículas , Oligonucleotídeos , Lipídeos , Microfluídica , Oligonucleotídeos Antissenso , Tamanho da PartículaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with no current effective therapeutics. One of the main reasons for the low efficacy of PDAC immunotherapy is the limited CD8+ T cell infiltration, without neo antigen present in PDAC. Aptamers represent single-stranded oligonucleotides which bind to specific targets with high specificity. We developed DNA conjugates and prepared diacyl phospholipid-aptamer XQ-2d which has potential for the targeted therapy and diagnosis of PDAC. In this study, flow cytometry and fluorescence microscopy were employed to assess whether the Lipo-XQ-2d probe could anchor on activated T cells to constitute ligands specifically recognizing PDAC PL45 cells. Flow cytometry was employed to determine cytotoxicity in activated T cells. Results showed that the Lipo-XQ-2d probe could be inserted into T cells, and was specifically bound to both T cells and PL45 cells. In addition, the Lipo-XQ-2d probe redirected T cells to kill PL45 cells in vitro and was not toxic to cells. In conclusion, lipid-DNA-aptamer-modified T-lymphocytes might effectively kill PDAC in vitro, supporting the clinical application of T cell adoptive immunotherapy.
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Aptâmeros de Nucleotídeos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Lipídeos , Linfócitos TRESUMO
We have developed a simple and versatile strategy for in situ growth of MnO2 on the surfaces of oleic acid-capped hydrophobic upconversion nanoparticles (UCNPs) by optimizing the component concentrations in the Lemieux-von Rudloff reagent. The oxidation time was shortened by a factor of two compared to that of the reported method. This oxidation process has no obvious adverse effects on the phases of UCNPs. STEM, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and energy-dispersive X-ray analysis (EDX) characterization demonstrated the successful growth of MnO2 on the surfaces of UCNPs. Furthermore, when the weight ratio of MnO2/UCNPs reached (147.61 ± 17.63) µg mg-1, 50% of the initial upconversion luminescence of UCNPs was quenched, as revealed by fluorescence and inductively coupled plasma optical emission spectrometry (ICP-OES) results. The presence of the surface MnO2 precipitate not only confers high dispersity of UCNPs in water, but also allows further activatable magnetic resonance imaging (MRI) and fluorescence multimodal imaging after reduction to Mn2+ by intracellular glutathione (GSH). A novel targeted drug carrier nanosystem was prepared to protect MnO2 from early decomposition in blood circulation by coating with mesoporous silica and capping with a gelatin nanolayer. Aptamer sgc8 was then attached to the surface of the gelatin nanolayer by covalent crosslinking to achieve targeted drug delivery. The results suggest that this nanosystem shows promise for further applications in cancer cell imaging and therapy.
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We designed an aptamer-based multifunctional ligand which, upon conjugation to the surface of upconversion nanoparticles (UCNPs), could realize phase transfer, covalent photosensitizer (PS) loading, and cancer cell targeting in one simple step. The as-built PDT nanodrug is selectively internalized into cancer cells and it exhibits highly efficient and selective cytotoxicity.
Assuntos
Aptâmeros de Nucleotídeos/química , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Humanos , Ligantes , FotoquimioterapiaRESUMO
Porphyrinic metal-organic framework (MOF) nanoparticles for photodynamic therapy solve the photosensitizer problems of poor solubility, self-quenching and aggregation. However, their low selectivity towards malignant tissues is an obstacle for bioimaging and a bottle-neck to cellular uptake for highly efficient photodynamic therapy of cancer. Here, ZrMOF nanoparticles as quenchers to conjugate DNA aptamers were developed for target-induced bioimaging and photodynamic therapy. A phosphate-terminal aptamer prepared by solid-phase DNA synthesis was anchored on the surface of ZrMOF nanoparticles through strong coordination between phosphate and zirconium. Based on π-π stacking-induced quenching of TAMRA by ZrMOF nanoparticles, target-induced imaging is achieved due to the structural change of the aptamer upon binding with the target. Aptamer-conjugated ZrMOF nanoparticles with target binding ability significantly enhanced the photodynamic therapy effect. Furthermore, phosphate-terminal aptamer conjugation method can be generalized to other types of MOF nanomaterials, such as UiO-66 and HfMOF nanoparticles, which can be potentially used in biochemistry.
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We propose a chelation-assisted assembly of multidentate CNs into metal-organic nanoparticles (MONs). Multidentate CNs functionalized with coordination sites participate equally as organic linkers in MON construction, which is driven by chelation between metal ions and coordination sites. MONs assembled from Au nanoparticles display particle number- and size-dependent optical properties. In addition, the resulting CN-assembled MONs give evidence that assembly was dictated by the multidentate surface ligand rather than the size, shape or material of CNs. With this chelation-assisted strategy, it is possible to control the number of assembled CNs and build the connections between them.