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1.
Nanoscale ; 13(30): 12848-12853, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477769

RESUMO

Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid "origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.


Assuntos
Nanoestruturas , RNA , DNA/genética , Terapia Genética , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , RNA/genética
2.
Nanotechnology ; 32(40)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34153957

RESUMO

In the past few decades, DNA nanotechnology has been developed a lot due to their appealing features such as structural programmability and easy functionalization. In the emerging field of DNA nanotechnology, DNA molecules are regarded not only as biological information carriers but also as building blocks in the assembly of various two-dimensional and three-dimensional nanostructures, serving as outstanding templates for the bottom-up fabrication of plasmonic nanostructures. By arranging nanoparticles with different components and morphologies on the predesigned DNA templates, various static and dynamic plasmonic nanostructures with tailored optical properties have been obtained. In this review, we summarized recent advances in the design and construction of static and dynamic DNA-based plasmonic nanostructures. In addition, we addressed their emerging applications in the fields of optics and biosensors. At the end of this review, the open questions and future directions of DNA-based plasmonic nanostructure are also discussed.

3.
Nat Commun ; 12(1): 2536, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953198

RESUMO

Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Humanos , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Estudos Prospectivos , Taxa de Sobrevida , Tetraspanina 30/metabolismo
4.
Nano Lett ; 21(8): 3573-3580, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33830773

RESUMO

The exploitation of strong light-matter interactions in chiral plasmonic nanocavities may enable exceptional physical phenomena and lead to potential applications in nanophotonics, information communication, etc. Therefore, a deep understanding of strong light-matter interactions in chiral plasmonic-excitonic (plexcitonic) systems constructed by a chiral plasmonic nanocavity and molecular excitons is urgently needed. Herein, we systematically studied the strong light-matter interactions in gold nanorod-based chiral plexcitonic systems assembled on DNA origami. Rabi splitting and anticrossing behavior were observed in circular dichroism spectra, manifesting chiroptical characteristic hybridization. The bisignate line shape of the circular dichroism (CD) signal allows the accurate discrimination of hybrid modes. A large Rabi splitting of ∼205/∼199 meV for left-handed/right-handed plexcitonic nanosystems meets the criterion of strong coupling. Our work deepens the understanding of light-matter interactions in chiral plexcitonic nanosystems and will facilitate the development of chiral quantum optics and chiroptical devices.


Assuntos
Nanopartículas Metálicas , Nanotubos , DNA , Ouro , Fenômenos Físicos
5.
ACS Appl Mater Interfaces ; 13(18): 20974-20981, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33909408

RESUMO

The CRISPR/Cas9 gene-editing system has become a promising strategy for tumor therapy with its powerful oncogene-editing ability. However, the efficient delivery of sgRNA/Cas9 complex into target tumor cells remains a challenge. Herein, we report a facile strategy for the construction of an sgRNA/Cas9 complex co-assembled nanoplatform for targeted gene editing and combined tumor therapy. In our design, the TAT peptide and thiolated DNA linker functionalized gold nanorod can efficiently load the sgRNA/Cas9 complex through the hybridization between the 3' overhang of sgRNA and the DNA linker. Due to the integration of an active cell targeting group (aptamer) and nuclear targeting peptide (TAT), the multifunctional nanoplatform can elicit the targeted cellular internalization and efficient nuclear targeting transportation to realize endogenous RNase H activated gene editing of the tumor-associated gene polo-like kinase 1 (PLK1). With mild photothermal treatment, this sgRNA/Cas9 complex loaded nanoplatform achieved efficient inhibition of tumor cell proliferation. This multifunctional nanocarrier provides a new strategy for the development of combined tumor therapy.


Assuntos
Edição de Genes , Ouro/química , Nanotubos/química , Neoplasias/terapia , Ácidos Nucleicos/química , Sistemas CRISPR-Cas , Proliferação de Células , Terapia Combinada , Humanos , Células MCF-7 , Microscopia Confocal , Neoplasias/patologia
6.
Nat Commun ; 12(1): 358, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441565

RESUMO

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.


Assuntos
Anticoagulantes/administração & dosagem , Aptâmeros de Nucleotídeos/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , DNA/administração & dosagem , Diálise Renal/métodos , Trombose/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/terapia , Animais , Aptâmeros de Nucleotídeos/química , DNA/química , Células HEK293 , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/ultraestrutura
7.
Nat Mater ; 20(3): 421-430, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32895504

RESUMO

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA 'locking strands' outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge.


Assuntos
Vacinas Anticâncer/imunologia , Melanoma Experimental/terapia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Apresentação do Antígeno , Bacteriófago M13/genética , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/genética , Testes Imunológicos de Citotoxicidade , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Concentração de Íons de Hidrogênio , Imunoterapia/métodos , Metástase Linfática/prevenção & controle , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Vacinas de DNA/administração & dosagem
9.
Nat Mater ; 20(3): 395-402, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33257794

RESUMO

Natural oxidases mainly rely on cofactors and well-arranged amino acid residues for catalysing electron-transfer reactions but suffer from non-recovery of their activity upon externally induced protein unfolding. However, it remains unknown whether residues at the active site can catalyse similar reactions in the absence of the cofactor. Here, we describe a series of self-assembling, histidine-rich peptides, as short as a dipeptide, with catalytic function similar to that of haem-dependent peroxidases. The histidine residues of the peptide chains form periodic arrays that are able to catalyse H2O2 reduction reactions efficiently through the formation of reactive ternary complex intermediates. The supramolecular catalyst exhibiting the highest activity could be switched between inactive and active states without loss of activity for ten cycles of heating/cooling or acidification/neutralization treatments, demonstrating the reversible assembly/disassembly of the active residues. These findings may aid the design of advanced biomimetic catalytic materials and provide a model for primitive cofactor-free enzymes.


Assuntos
Materiais Biomiméticos/química , Nanoestruturas/química , Oxirredutases/química , Peptídeos/química , Catálise , Dicroísmo Circular , Coenzimas , Cristalografia por Raios X , Histidina/química , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Peróxido de Hidrogênio/química , Modelos Moleculares , Oxirredução , Oxirredutases/metabolismo , Conformação Proteica , Relação Quantitativa Estrutura-Atividade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
Angew Chem Int Ed Engl ; 60(5): 2594-2598, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33089613

RESUMO

Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.


Assuntos
Terapia Combinada/métodos , DNA/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos
11.
Angew Chem Int Ed Engl ; 60(4): 1853-1860, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33058467

RESUMO

Chemically modified DNA has been widely developed to fabricate various nucleic acid nanostructures for biomedical applications. Herein, we report a facile strategy for construction of branched antisense DNA and small interfering RNA (siRNA) co-assembled nanoplatform for combined gene silencing in vitro and in vivo. In our design, the branched antisense can efficiently capture siRNA with 3' overhangs through DNA-RNA hybridization. After being equipped with an active targeting group and an endosomal escape peptide by host-guest interaction, the tailored nucleic acid nanostructure functions efficiently as both delivery carrier and therapeutic cargo, which is released by endogenous RNase H digestion. The multifunctional nucleic acid nanosystem elicits an efficient inhibition of tumor growth based on the combined gene silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This biocompatible nucleic acid nanoplatform presents a new strategy for the development of gene therapy.


Assuntos
Inativação Gênica , Terapia Genética , Nanopartículas/química , Neoplasias/terapia , RNA Antissenso/química , RNA Interferente Pequeno/química , Animais , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Estudo de Prova de Conceito , Interferência de RNA
12.
Adv Healthc Mater ; 9(19): e2001046, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32864890

RESUMO

During the past decades, nucleic acids have been employed for the construction of versatile nanostructures with well-defined shapes and sizes. Owing to the remarkable programmability, addressability, and biocompatibility, nucleic acid nanostructures are extensively applied in biomedical researches, such as bioimaging, biosensing, and drug delivery. In particular, nucleic acid nanostructures can act as promising candidates for the delivery of gene-related nucleic acid drugs based on the inherent homology. In this review, the recent progress in the design of multifunctional nucleic acid nanocarriers for gene therapy through antisense, RNA interference, gene editing, and gene expression is summarized. Furthermore, the challenges and future opportunities of nucleic acid nanotechnology in biomedical applications will be discussed.


Assuntos
Nanoestruturas , Ácidos Nucleicos , DNA , Sistemas de Liberação de Medicamentos , Terapia Genética , Nanotecnologia
13.
ACS Appl Mater Interfaces ; 12(29): 32461-32467, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32613824

RESUMO

DNA nanostructures have garnered considerable interest as research tools in the field of cell biology and pathology. Herein, we develop an addressable double-bundle DNA tetrahedron with distinct modification sites to load multiple functional components for efficient regulation of gene expression. In our tailored nanoplatform, nucleic acid drugs (antisense for gene therapy) and protein drugs (KillerRed for photodynamic therapy) are precisely organized in the chemically well-defined DNA tetrahedron. With the attachment of active targeting groups, this functional DNA nanocarrier can efficiently penetrate into the cell membrane and subsequently transport drugs to the target subcellular organelles (mitochondrion and nucleus) for inducing synergistic cell behavior regulation to start the endogenous apoptotic process. This tailored DNA nanocarrier provides unprecedented opportunities for intelligent drug delivery and cell biology research.


Assuntos
DNA/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Terapia Genética , Humanos , Nanoestruturas/química , Tamanho da Partícula , Fotoquimioterapia , Propriedades de Superfície
14.
Chem Commun (Camb) ; 56(68): 9894-9897, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32720666

RESUMO

A terminal-closed linear gene with strong exonuclease resistance and serum stability was successfully constructed by polymerase chain reaction (PCR) with an α-l-threose nucleic acid (TNA) loop modified primer pair, which can be used as an efficient gene expression system in eukaryotic cells for gene delivery.


Assuntos
Primers do DNA/química , Ácidos Nucleicos/química , Tetroses/química , Transfecção/métodos , Primers do DNA/metabolismo , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Microscopia de Fluorescência , Plasmídeos/genética , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase
15.
J Am Chem Soc ; 142(27): 11680-11684, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32564606

RESUMO

Shape complementarity is of paramount importance in molecular recognition, but has rarely been adopted in the self-assembly of colloidal particles, especially in the case of nanoparticles of different shapes. Here, we demonstrated a simple, yet powerful strategy for fabricating gold nanoring-based heterogeneous nanostructures (AuNR-HNs) with well-defined geometries and high yield. The assembly of various geometries of AuNR-HNs is modulated by the shape complementarity of plasmonic nanorings and nanospheres. We also present experimental evidence of dark quadrupolar ring mode excitation in AuNR-HNs through single-particle optical measurements. Our strategy will be beneficial in the study of nanoparticle assembly, photonic element interaction, and the development of plasmon-based optical devices.


Assuntos
Ouro/química , Nanosferas/química , Nanoestruturas/química , Tamanho da Partícula , Propriedades de Superfície
16.
Chembiochem ; 21(17): 2408-2418, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32227615

RESUMO

Nanomaterials with enzyme-mimicking behavior (nanozymes) have attracted a lot of research interest recently. In comparison to natural enzymes, nanozymes hold many advantages, such as good stability, ease of production and surface functionalization. As the catalytic mechanism of nanozymes is gradually revealed, the application fields of nanozymes are also broadly explored. Beyond traditional colorimetric detection assays, nanozymes have been found to hold great potential in a variety of biomedical fields, such as tumor theranostics, antibacterial, antioxidation and bioorthogonal reactions. In this review, we summarize nanozymes consisting of different nanomaterials. In addition, we focus on the catalytic performance of nanozymes in biomedical applications. The prospects and challenges in the practical use of nanozymes are discussed at the end of this Minireview.

17.
Adv Mater ; 32(21): e2000294, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32301202

RESUMO

DNA origami has been widely investigated as a template for the organization of various functional elements, leading to potential applications in many fields such as biosensing, nanoelectronics, and nanophotonics. However, the synthesis of inorganic nonmetallic nanomaterials with predesigned patterns using DNA origami templates has seldom been explored. Here, a novel method is reported to site-specifically synthesize silica nanostructures with designed patterns on DNA origami templates. The molecular dynamic simulation confirms that the positively charged silica precursors have a stronger electrostatic affinity to protruding double-stranded DNA (dsDNA) than DNA origami surfaces. The work describes a novel strategy to fabricate silica nanostructures with nanoscale precision. Moreover, the site-specific silicification of DNA nanoarchitectures expands the scope of customized synthesis of inorganic nonmetallic nanomaterials.


Assuntos
DNA/química , Nanoestruturas/química , Nanotecnologia , Dióxido de Silício/química , Técnicas de Química Sintética , Simulação de Dinâmica Molecular , Propriedades de Superfície
18.
J Am Chem Soc ; 141(48): 19032-19037, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31729871

RESUMO

Precisely assembled DNA nanostructures are promising candidates for the delivery of biomolecule-based therapeutics. Herein, we introduce a facile strategy for the construction of a branched DNA-based nanoplatform for codelivery of gene editing (sgRNA/Cas9, targeting DNA in the nucleus) and gene silencing (antisense, targeting mRNA in the cytoplasm) components for synergistic tumor therapy in vitro and in vivo. In our design, the branched DNA structure can efficiently load a sgRNA/Cas9/antisense complex targeting a tumor-associated gene, PLK1, through DNA self-assembly. With the incorporation of an active targeting aptamer and an endosomal escape peptide by host-guest interaction, the biocompatible DNA nanoplatform demonstrates efficient inhibition of tumor growth without apparent systemic toxicity. This multifunctional DNA nanocarrier provides a new strategy for the development of gene therapeutics.


Assuntos
Neoplasias da Mama/terapia , Sistemas CRISPR-Cas , DNA/química , Edição de Genes/métodos , RNA Antissenso/administração & dosagem , RNA Guia/administração & dosagem , Animais , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Feminino , Terapia Genética/métodos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , RNA Antissenso/genética , RNA Antissenso/uso terapêutico , RNA Guia/genética , RNA Guia/uso terapêutico
19.
J Am Chem Soc ; 141(45): 17968-17972, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31660742

RESUMO

The development of facile techniques for precisely patterning complex metal and metal oxide nanostructures is essential for catalytic nanosystems and optical and electronic nanodevices. Herein, we report a general strategy for designing and fabricating metal and metal oxide nanoclusters (MMONs) with arbitrarily prescribed patterns on DNA origami templates. The valuable feature of our approach lies in the site-specific arrangement of thiol groups on DNA origami, which act as reaction centers, initiating in situ MMONs growth. This strategy can be generalized to the patterning of arbitrary geometries and various inorganic materials, which will aid the generation of complex and precisely arranged components for customized functional nanoarchitectures.


Assuntos
DNA/química , Nanopartículas/química , Óxidos/química , Compostos de Sulfidrila/química , Compostos Férricos/química
20.
Angew Chem Int Ed Engl ; 58(40): 14224-14228, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389144

RESUMO

The targeted delivery of chemotherapeutic drugs is a major challenge in the clinical treatment of cancer. Herein, we constructed a multifunctional DNA nanoplatform as a versatile carrier of the highly potent platinum-based DNA intercalator, 56MESS. In our rational design, 56MESS was efficiently loaded into the double-bundle DNA tetrahedron through intercalation with the DNA duplex. With the integration of a nanobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNA nanocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapy without obvious systemic toxicity. This DNA-based platinum-drug delivery system provides a promising strategy for the treatment of tumors.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , DNA/química , Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Compostos Organoplatínicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química
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