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1.
ACS Appl Mater Interfaces ; 12(10): 11329-11340, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32072808

RESUMO

Designing a multifunctional theranostic nanoplatform with optional therapeutic strategies is highly desirable to select the most suitable therapeutic manners for the patient's cancer treatment. Among all shapes of silver materials, a silver nanoprism was reported to have great potential in photothermal therapy (PTT) owing to its strong surface plasmon resonance band in the near-infrared region. However, its instability in physicochemical environments and its severe toxicity confined its further application. To overcome this, herein, we demonstrated a silver prism-polydopamine (PDA) hybrid nanoplatform for tumor treatment with three therapeutic strategies. Specifically, the PDA coating endows the silver prism with excellent stability, high photothermal conversion, long-term in vivo biocompatibility, ease of decorating targeting ligands, and drug delivery. Upon near-infrared laser irradiation (808 nm, 1 W/cm2), tumors can be eradicated by the as-prepared nanoparticle through monomodal PTT. Besides, when combined with a chemical drug, this nanoparticle is able to inhibit tumor growth via combined photochemotherapy under a lower laser treatment (0.7 W/cm2). Furthermore, by supplementing with an immune checkpoint blockade, the realized synergistic photochemoimmunotherapy exhibits high efficacy to inhibit tumor relapse and metastasis. Moreover, owing to the high photothermal conversion efficiency and great X-ray attenuation ability of the silver nanoprism, our designed nanoplatform can be used in photoacoustic, computed tomography, and infrared thermal multimodal imaging. Our study provides a multifunctional nanoparticle for tumor theranostics, and this therapeutic strategy-optional nanoplatform shows promise in future biomedicine.

2.
Adv Mater ; 31(46): e1905825, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566283

RESUMO

Synergistic phototherapy has the potential to conquer the extreme heterogeneity and complexity of difficult tumors and result in better cancer treatment outcomes than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). However, the previous approaches to combining PDT and PTT are mainly focused on primary tumor obliteration while neglecting tumor metastasis, which is responsible for about 90% of cancer deaths. It is shown that a combined PDT/PTT approach, based on upconversion-polymer hybrid nanoparticles with surface-loaded chlorin e6 photosensitizer, can enhance primary tumor elimination and elicit antitumor immunity against disseminated tumors. The specifical arrangement of an external upconversion coating over the polymer core ensures adequate photoabsorption by the upconversion nanoparticles for the generation of reactive oxygen species upon single near-infrared light irradiation. Furthermore, it is found that synergistic phototherapy can elicit robust systemic and humoral antitumor immune responses. When combined with immune checkpoint blockades, it can inhibit tumor relapse and metastasis as well as prolong the survival of tumor-bearing mice in two types of tumor metastasis models. This study may establish a new modality for enhancing immunogenic cell death through a synergistic phototherapeutic nanoplatform and extend this strategy to overcome tumor metastasis with an augmented antitumor immune response.

3.
Anal Chem ; 91(2): 1619-1626, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30561989

RESUMO

Cell signaling is a fast, dynamic, and complex process, which controls a variety of critical physiological functions. Methods to investigate such dynamic information, however, suffer from limited throughput in the single-cell level and a lack of precise fluid manipulation. Herein, we present a new strategy, termed dynamic microfluidic cytometry (DMC), for high-throughput probing of G protein-coupled receptor (GPCR) signaling in single-cell resolution (single-cell cellomics analysis) by creatively applied cyclical cell trapping, stimulating, and releasing automatically. Dose-response curves and half-maximal effective concentration (EC50) values for HeLa cells treated with adenosine triphosphate (ATP), histamine (HA), and acetylcholine chloride (ACH) were successfully obtained in the single-cell level. High-throughput single-cell dynamic signaling was further implemented by sequential or simultaneous stimulation, which revealed that different mechanisms were working in triggering intracellular calcium release. In addition, simultaneous stimulation to two different types of cells, HeLa and NIH-3T3 cells, was also successfully realized, which was crucial for online comparison of dynamic signaling of different types of cells. We believe that the proposed DMC provides a versatile means for high-throughput probing single-cell dynamic signaling, which is potentially useful in chemical biology, cell biology, and pharmacology.

4.
Anal Chem ; 89(22): 12039-12044, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29072078

RESUMO

The circulating tumor cells (CTCs) in the blood allow the noninvasive analysis of metastatic mechanisms, cancer diagnosis, prognosis, disease monitoring, and precise therapy through "liquid biopsies". However, there is no integrated and robust multifunctional microchip, which not only could highly efficient capture CTCs, but also fast release and lyse cells on one single chip without using other biochemical agents for downstream biomedical analysis. In this work, we integrated the three functions in one electrochemical microchip (echip) by intentionally designing a cactus-like, topologically structured conductive array consisted of a PDMS micropillar-array core and an electroconductive gold coating layer with hierarchical structure. The echip presented a capture efficiency of 85-100% for different cell lines in both buffer solution and whole blood. Moreover, the validity of the echip was further evaluated by using non-small-cell lung cancer patient samples. The electrochemical released cells or lysed-cell solutions could be obtained within 10 min and have been successfully used for mutant detection by DNA sequencing or RT-PCR. The fast release at a relative low voltage (-1.2 V) was originating from an electrochemical cleavage of the Au-S bonds that immobilized antibody on the chip. The electrochemical lysis took place at a high voltage (20 V) with an admirable performance. Thus, the highly integrated multifunctional echip was well demonstrated and promised a significant application in the clinical field.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Técnicas Eletroquímicas , Neoplasias Pulmonares/patologia , Análise em Microsséries , Células Neoplásicas Circulantes/patologia , Humanos , Tamanho da Partícula , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Propriedades de Superfície , Células Tumorais Cultivadas
5.
Anal Chem ; 89(17): 9209-9217, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28791865

RESUMO

Cellular environments are inherently dynamic and generally involve complex, temporally varying signals. Reconstruction of these environments with high spatial and temporal fidelity and simultaneous imaging of intracellular dynamics in live cells remains a major challenge. In this paper, a microfluidic chemical function generator (µCFG) was proposed for probing cell dynamic signaling with high temporal resolution. By combining a hydrodynamic gating module with a chaotic advection mixing module, the µCFG was able to generate a variety of chemical waveforms, such as digital pulsatile chemical waveforms with a frequency higher than 10 Hz and analog chemical waveforms with a frequency higher than 0.2 Hz. The shape, frequency, amplitude, and duty cycle of the waveforms could be also conveniently modulated. To demonstrate the capability of µCFG of probing fast biological processes and elucidate signal transduction pathways in complex signaling networks, a variety of temporal responses of Ca2+ signaling to ATP-induced activation of the P2Y receptor, a prototypical G-protein coupled receptor (GPCR), were investigated in live cells by precisely and dynamically controlling their microenvironment.


Assuntos
Sinalização do Cálcio/fisiologia , Comunicação Celular/fisiologia , Fibroblastos/fisiologia , Dispositivos Lab-On-A-Chip , Animais , Camundongos , Células NIH 3T3
6.
Anal Chem ; 89(6): 3716-3723, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28211674

RESUMO

Digital loop-mediated isothermal amplification (dLAMP) is an attractive approach for absolute quantification of nucleic acids with high sensitivity and selectivity. Theoretical and numerical analysis of dLAMP provides necessary guidance for the design and analysis of dLAMP devices. In this work, a mathematical model was proposed on the basis of the Monte Carlo method and the theories of Poisson statistics and chemometrics. To examine the established model, we fabricated a spiral chip with 1200 uniform and discrete reaction chambers (9.6 nL) for absolute quantification of pathogenic DNA samples by dLAMP. Under the optimized conditions, dLAMP analysis on the spiral chip realized quantification of nucleic acids spanning over 4 orders of magnitude in concentration with sensitivity as low as 8.7 × 10-2 copies/µL in 40 min. The experimental results were consistent with the proposed mathematical model, which could provide useful guideline for future development of dLAMP devices.


Assuntos
DNA/análise , Modelos Estatísticos , Técnicas de Amplificação de Ácido Nucleico , DNA/genética , Método de Monte Carlo , Imagem Óptica , Reação em Cadeia da Polimerase em Tempo Real
7.
ACS Appl Mater Interfaces ; 8(49): 33457-33463, 2016 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960420

RESUMO

The circulating tumor cells (CTCs), originating from the primary tumor, play a vital role in cancer diagnosis, prognosis, disease monitoring, and precise therapy. However, the CTCs are extremely rare in the peripheral bloodstream and hard to be isolated. To overcome current limitations associated with CTC capture and analysis, the strategy incorporating nanostructures with microfluidic devices receives wide attention. Here, we demonstrated a three-dimensional microfluidic device (Rm-chip) for capturing cancer cells with high efficiency by integrating a novel hierarchical structure, the "Rhipsalis (Cactaceae)"-like micropillar array, into the Rm-chip. The PDMS micropillar array was fabricated by soft-lithography and rapid prototyping method, which was then conformally plated with a thin gold layer through electroless plating. EpCAM antibody was modified onto the surface of the micropillars through the thiol-oligonucleotide linkers in order to release captured cancer cells by DNase I treatment. The antibody-functionalized device achieved an average capture efficiency of 88% in PBS and 83.7% in whole blood samples. We believe the Rm-chip provided a convenient, economical, and versatile approach for cell analysis with wide potential applications.


Assuntos
Microfluídica , Cactaceae , Linhagem Celular Tumoral , Separação Celular , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Células Neoplásicas Circulantes
8.
Adv Mater ; 28(18): 3543-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26991071

RESUMO

Heterogeneous 3D cell microenvironment arrays are rapidly assembled by combining surface-wettability-guided assembly and microdroplet-array-based operations. This approach enables precise control over individual shapes, sizes, chemical concentrations, cell density, and 3D spatial distribution of multiple components. This technique provides a cost-effective solution to meet the increasing demand of stem cell research, tissue engineering, and drug screening.


Assuntos
Microambiente Celular , Engenharia Tecidual
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