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1.
J Am Chem Soc ; 142(1): 382-391, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31801020

RESUMO

The inner region of solid tumors is found to be high-pressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor bulk. By using an apoptotic body (AB) as the carrier, we develop an effective and universal intratumoral nanomedicine delivery system for the long-lasting remission of tumors. Our results show that the AB-encapsulated nanomedicine (using CpG immunoadjuvant-modified gold-silver nanorods as a model), after intravenous injection, can be specifically phagocytosed by inflammatory Ly-6C+ monocytes, which then actively infiltrate the tumor center via their natural tumor-homing tendency. With the integration of AB-facilitated intratumoral accumulation, the nanorod-based photothermal effect, and CpG-promoted immunostimulation, this cell-mediated delivery system can not only efficiently ablate primary tumors but also elicit a potent immunity to prevent tumors from metastasizing and recurring.

2.
Polymers (Basel) ; 11(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703463

RESUMO

Soy protein isolate (SPI) has attracted considerable attention in the field of packaging technology due to its easy processability, biodegradability, and good film-forming characteristics. However, SPI-based films often suffer from inferior mechanical properties and high moisture sensitivity, thus restricting their practical application. In the present study, herein, a biobased nanocomposite film was developed by cross-linking SPI matrix from the synergistic reinforcement of cellulose nanofibers (CNF) and nano-silica (NS) particles. First, we functionalized the CNF with NS using a silane agent (KH560) as an efficient platform to enhance the interfacial interaction between SPI and CNF/NS, resulting from the epoxy-dominated cross-linking reaction. The chemical structure, thermal stability, and morphology of the resultant nanocomposite films were comprehensively investigated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). These results supported successful surface modification and indicated that the surface-tailored CNF/NS nanohybrid possesses excellent adhesion with SPI matrix through covalent and hydrogen-bonding interactions. The integration of CNF/NS into SPI resulted in nanocomposite films with an improved tensile strength (6.65 MPa), representing a 90.54% increase compared with the pristine SPI film. Moreover, the resulting composites had a significantly decreased water vapor permeation and a higher water contact angle (91.75°) than that of the unmodified film. The proposed strategy of synergistic reinforcements in the biobased composites may be a promising and green approach to address the critical limitations of plant protein-based materials in practical applications.

3.
J Am Chem Soc ; 141(46): 18421-18427, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31584808

RESUMO

Aptamers and antibodies, as molecular recognition probes, play critical roles in cancer diagnosis and therapy. However, their recognition ability is based on target overexpression in disease cells, not target exclusivity, which can cause on-target off-tumor effects. To address the limitation, we herein report a novel strategy to develop a conditional aptamer conjugate which recognizes its cell surface target, but only after selective activation, as determined by characteristics of the disease microenvironment, which, in our model, involve tumor hypoxia. This conditional aptamer is the result of conjugating the aptamer with PEG5000-azobenzene-NHS, which is responsive to hypoxia, here acting as a caging moiety of conditional recognition. More specifically, the caging moiety is unresponsive in the intact conjugate and prevents target recognition. However, in the presence of sodium dithionite or hypoxia (<0.1% O2) or in the tumor microenvironment, the caging moiety responds by allowing conditional recognition of the cell-surface target, thereby reducing the chance of on-target off-tumor effects. It is also confirmed that the strategy can be used for developing a conditional antibody. Therefore, this study demonstrates an efficient strategy by which to develop aptamer/antibody-based diagnostic probes and therapeutic drugs for cancers with a unique hypoxic microenvironment.

4.
Chemistry ; 25(8): 1895-1900, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30681205

RESUMO

A series of physiological barriers have impeded nanoparticle-based drug formulations (NDFs) from reaching their targeted sites and achieving therapeutic outcomes. In this study, we develop size-controllable stealth doxorubicin-loaded nanodrug coated with CD47 peptides (DOX/sNDF-CD47) based on supramolecular chemistry to overcome multiple biological barriers. The smart DOX/sNDF-CD47 can efficiently decrease sequestration by macrophages and disassemble into poly(amidoamine) dendrimers with nuclear localization sequences (DOX/PAMAM-NLS) in the presence of matrix metalloproteinase-2 (MMP-2). Such structure transformation endows DOX/sNDF-CD47 with the ability of deep penetration in multicellular tumor spheroid, lysosomal escape, and nucleus localization, resulting in excellent cytotoxicity and drug resistance combating. In vivo experiments further confirmed that DOX/sNDF-CD47 has good tumor-targeting ability and can significantly improve therapeutic efficacy of DOX on xenograft tumor model. The ability to overcome multiple biological barriers makes sNDF-CD47 a promising NDFs to treat cancer expressing MMP-2 and combating drug resistance.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos , Resistência a Medicamentos/efeitos dos fármacos , Metaloproteinase 2 da Matriz , Nanopartículas , Animais , Antineoplásicos/uso terapêutico , Dendrímeros , Doxorrubicina/uso terapêutico , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Tecidual
5.
J Am Chem Soc ; 139(27): 9128-9131, 2017 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-28635257

RESUMO

Aptamers are powerful candidates for molecular imaging and targeted therapy of cancer based on such appealing features as high binding affinity, high specificity, site-specific modification and rapid tumor penetration. However, aptamers are susceptible to plasma exonucleases in vivo. This seriously affects their in vivo applications. To overcome this key limitation, we herein report the design and development of circular bivalent aptamers. Systematic studies reveal that cyclization of aptamers can improve thermal stability, nuclease resistance and binding affinity. In vivo fluorescence imaging further validates the efficient accumulation and retention of circular bivalent aptamers in tumors compared to "mono-aptamers". Therefore, this study provides a simple and efficient strategy to boost in vivo aptamer applications in cancer diagnosis and therapy.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias/diagnóstico por imagem , Aptâmeros de Nucleotídeos/síntese química , Ciclização , Humanos , Imagem Óptica , Temperatura
6.
Biosens Bioelectron ; 92: 40-46, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28187297

RESUMO

A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets.


Assuntos
Adenosina/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Cocaína/análise , Inibidores da Captação de Dopamina/análise , Corantes Fluorescentes/química , Imidas/química , Perileno/análogos & derivados , Adenosina/sangue , Carbocianinas/química , Cocaína/sangue , Inibidores da Captação de Dopamina/sangue , Humanos , Limite de Detecção , Perileno/química , Espectrometria de Fluorescência/métodos
7.
Biosens Bioelectron ; 89(Pt 1): 201-211, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27020066

RESUMO

In clinical diagnostics, as well as food and environmental safety practices, biosensors are powerful tools for monitoring biological or biochemical processes. Two-dimensional (2D) transition metal nanomaterials, including transition metal chalcogenides (TMCs) and transition metal oxides (TMOs), are receiving growing interest for their use in biosensing applications based on such unique properties as high surface area and fluorescence quenching abilities. Meanwhile, nucleic acid probes based on Watson-Crick base-pairing rules are also being widely applied in biosensing based on their excellent recognition capability. In particular, the emergence of functional nucleic acids in the 1980s, especially aptamers, has substantially extended the recognition capability of nucleic acids to various targets, ranging from small organic molecules and metal ions to proteins and cells. Based on π-π stacking interaction between transition metal nanosheets and nucleic acids, biosensing systems can be easily assembled. Therefore, the combination of 2D transition metal nanomaterials and nucleic acids brings intriguing opportunities in bioanalysis and biomedicine. In this review, we summarize recent advances of nucleic acid-functionalized transition metal nanosheets in biosensing applications. The structure and properties of 2D transition metal nanomaterials are first discussed, emphasizing the interaction between transition metal nanosheets and nucleic acids. Then, the applications of nucleic acid-functionalized transition metal nanosheet-based biosensors are discussed in the context of different signal transducing mechanisms, including optical and electrochemical approaches. Finally, we provide our perspectives on the current challenges and opportunities in this promising field.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Metais/química , Nanoestruturas/química , Ácidos Nucleicos/química , Animais , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Humanos , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Elementos de Transição/química
8.
Chem Soc Rev ; 45(9): 2583-602, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-26954935

RESUMO

The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson-Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , DNA/química , DNA/metabolismo , Imagem Molecular/métodos , Nanotecnologia/métodos , Neoplasias/terapia , Animais , Humanos , Neoplasias/patologia
9.
Chem Soc Rev ; 45(5): 1410-31, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26758955

RESUMO

Hydrogels are crosslinked hydrophilic polymers that can absorb a large amount of water. By their hydrophilic, biocompatible and highly tunable nature, hydrogels can be tailored for applications in bioanalysis and biomedicine. Of particular interest are DNA-based hydrogels owing to the unique features of nucleic acids. Since the discovery of the DNA double helical structure, interest in DNA has expanded beyond its genetic role to applications in nanotechnology and materials science. In particular, DNA-based hydrogels present such remarkable features as stability, flexibility, precise programmability, stimuli-responsive DNA conformations, facile synthesis and modification. Moreover, functional nucleic acids (FNAs) have allowed the construction of hydrogels based on aptamers, DNAzymes, i-motif nanostructures, siRNAs and CpG oligodeoxynucleotides to provide additional molecular recognition, catalytic activities and therapeutic potential, making them key players in biological analysis and biomedical applications. To date, a variety of applications have been demonstrated with FNA-based hydrogels, including biosensing, environmental analysis, controlled drug release, cell adhesion and targeted cancer therapy. In this review, we focus on advances in the development of FNA-based hydrogels, which have fully incorporated both the unique features of FNAs and DNA-based hydrogels. We first introduce different strategies for constructing DNA-based hydrogels. Subsequently, various types of FNAs and the most recent developments of FNA-based hydrogels for bioanalytical and biomedical applications are described with some selected examples. Finally, the review provides an insight into the remaining challenges and future perspectives of FNA-based hydrogels.


Assuntos
Pesquisa Biomédica , Técnicas Biossensoriais , DNA/química , Hidrogéis/química , Animais , Humanos
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