Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Biomol Struct Dyn ; : 1-9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31872783

RESUMO

Src homology 3 (SH3) domains are small protein modules involved in the regulation of important cellular pathways such as proliferation and migration, which canonically prefer to recognize and interact with proline-rich peptide ligands with class I or class II motif. Previously, we identified two self-binding peptides (SBPs) in human c-Src tyrosine kinase, of which the first SBP (fSBP) segment (248SKPQTQGLAK257) fulfills intramolecular interaction with the kinase SH3 domain to regulate the kinase function. The segment (and its equivalents in other c-Src family members) does not contain canonical class II motif (PxxQxL versus PxxPx+), but can bind to SH3 domain in a routine class II mode. Existing theories such as non-polyproline-II binding conformation, unusual peptide-binding pocket and extensive use of contacts cannot explain this atypical recognition phenomenon. Here, we performed a systematic investigation of SH3-fSBP binding in different conditions, including the segment in full-length kinase or in isolated state, the kinase in different forms and the fSBP residue mutations, by using microsecond molecular dynamics simulations, conformational clustering analyses and binding energetics calculations. We purposed a new mechanism that the protein context is primarily responsible for the atypical intramolecular SH3-fSBP recognition in c-Src kinase, which can promote the tight packing of segment against domain surface, support the segment polyproline-II (PPII) conformation in unbound state, and avoid unfavorable segment interactions with SH3 charged region by forming a C-terminal t-turn. In addition, the only proline residue Pro250 of fSBP segment is also required for the segment recognition by SH3 domain in c-Src kinase context; lack of Pro250 residue the segment exhibits considerable disorder and cannot maintain in PPII helical conformation, thus largely impairing the domain-segment binding capability. Further binding analysis confirms that the isolated fSBP peptide cannot bind effectively to SH3 domain out of kinase context, whereas its mutant version, i.e. fSBP(Q253P/L255R) peptide, which possesses the canonical class II motif, exhibits an increased affinity to the domain.Communicated by Ramaswamy H. Sarma.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31799247

RESUMO

Optical imaging plays an indispensable role in biology and medicine attributing to its noninvasiveness, high spatiotemporal resolution, and high sensitivity. However, as a conventional optical imaging modality, fluorescence imaging confronts issues of shallow imaging depth due to the need for real-time light excitation which produces tissue autofluorescence. By contrast, self-luminescence imaging eliminates the concurrent light excitation, permitting deeper imaging depth and higher signal-to-background ratio (SBR), which has attracted growing attention. Herein, this review summarizes the progress on the development of near-infrared (NIR) emitting self-luminescence agents in deep-tissue optical imaging with highlighting the design principles including molecular- and nano-engineering approaches. Finally, it discusses current challenges and guidelines to develop more effective self-illuminating agents for biomedical diagnosis and treatment.

3.
Bioconjug Chem ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31765561

RESUMO

Inorganic nanoparticles as a versatile nanoplatform have been broadly applied in the diagnosis and treatment of cancers due to their inherent superior physicochemical properties (including magnetic, thermal, optical, and catalytic performance) and excellent functions (e.g., imaging, targeted delivery, and controlled release of drugs) through surface functional modification or ingredient dopant. However, in practical biological applications, inorganic nanomaterials are relatively difficult to degrade and excrete, which induces a long residence time in living organisms and thus may cause adverse effects, such as inflammation and tissue cysts. Therefore, the development of biodegradable inorganic nanomaterials is of great significance for their biomedical application. This Review will focus on the recent advances of degradable inorganic nanoparticles for cancer theranostics with highlight on the degradation mechanism, aiming to offer an in-depth understanding of degradation behavior and related biomedical applications. Finally, key challenges and guidelines will be discussed to explore biodegradable inorganic nanomaterials with minimized toxicity issues, facilitating their potential clinical translation in cancer diagnosis and treatment.

4.
J Am Chem Soc ; 141(27): 10581-10584, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31259544

RESUMO

Real-time multiplex imaging is imperative to biology and diagnosis but remains challenging for optical modality. Herein, a unimolecular chemo-fluoro-luminescent reporter (CFR) is synthesized for duplex imaging of drug-induced hepatotoxicity (DIH), a long-term medical concern. CFR simultaneously detects superoxide anion (O2•-) and caspase-3 (casp3) through respective activation of its independent chemiluminescence and near-infrared fluorescence channels. Such a crosstalk-free duplex imaging capability of CFR enables longitudinal measurement of two correlated biomolecular events (oxidative stress and cellular apoptosis) during the progression of DIH, identifying O2•- as an earlier biomarker for detection of DIH both in vitro and in vivo. Moreover, CFR detects DIH 17.5 h earlier than histological changes. Thus, our study not only develops a sensitive optical reporter for early detection of DIH but also provides a general molecular design strategy for duplex imaging.

5.
Nat Commun ; 10(1): 2064, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048701

RESUMO

Afterglow imaging with long-lasting luminescence after cessation of light excitation provides opportunities for ultrasensitive molecular imaging; however, the lack of biologically compatible afterglow agents has impeded exploitation in clinical settings. This study presents a generic approach to transforming ordinary optical agents (including fluorescent polymers, dyes, and inorganic semiconductors) into afterglow luminescent nanoparticles (ALNPs). This approach integrates a cascade photoreaction into a single-particle entity, enabling ALNPs to chemically store photoenergy and spontaneously decay it in an energy-relay process. Not only can the afterglow profiles of ALNPs be finetuned to afford emission from visible to near-infrared (NIR) region, but also their intensities can be predicted by a mathematical model. The representative NIR ALNPs permit rapid detection of tumors in living mice with a signal-to-background ratio that is more than three orders of magnitude higher than that of NIR fluorescence. The biodegradability of the ALNPs further heightens their potential for ultrasensitive in vivo imaging.


Assuntos
Engenharia Química/métodos , Microscopia Intravital/métodos , Imagem Molecular/métodos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Animais , Linhagem Celular Tumoral/transplante , Estudos de Viabilidade , Feminino , Corantes Fluorescentes/química , Luminescência , Camundongos , Camundongos Nus , Microscopia de Fluorescência/métodos , Nanotecnologia/métodos , Sensibilidade e Especificidade
6.
Mol Omics ; 15(4): 280-295, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31112188

RESUMO

Many cell signaling pathways are orchestrated by the weak, transient, and reversible protein-protein interactions that are mediated by the binding of a short peptide segment in one protein (parent protein) to a globular domain in another (partner protein), known as peptide-mediated interactions (PMIs). Previous studies normally had an implicit hypothesis that a PMI is functionally equivalent or analogous to the protein-peptide interaction (PTI) involved in the PMI system, while ignoring parent context contribution to the peptide binding. Here, we perform a systematic investigation on the reasonability and applicability of the hypothesis at structural, energetic and dynamic levels. It is revealed that the context impacts PMIs primarily through conformational constraint of the peptide segments, which can (i) reduce the peptide flexibility and disorder in an unbound state, (ii) help the peptide conformational selection to fit the active pocket of partner proteins, and (iii) enhance the peptide packing tightness against the partners. Long, unstructured and/or middle-located peptide segments seem to be more vulnerable to their context than short, structured and/or terminal ones. The context is found to moderately or considerably improve both the binding affinity and specificity of PMIs as compared to their PTI counterparts; with the context support a peptide segment can contribute to ∼30-60% total binding energy of the whole PMI system, whereas the contribution is reduced to ∼5-50% when the context constraint is released. In addition, we also observe that peptide selectivity is largely impaired or even reversed upon stripping of their parent context (global selectivity decreases from 34.2 to 1.7-fold), by examining the crystal structures of full-length Src family kinases in an autoinhibitory state. Instead of the direct interaction and desolvation that are primarily concerned in traditional studies, peptide flexibility and the entropy penalty should also play a crucial role in the context effect on PMIs. Overall, we suggest that the context factor should not be ignored in most cases, particularly those with peptide segments that are long, highly disordered, and/or located at the middle region of their parent proteins.

7.
Nat Mater ; 18(10): 1133-1143, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31133729

RESUMO

Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-ß-D-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.

8.
J Theor Biol ; 469: 25-34, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30802465

RESUMO

Self-binding peptide (SBP) represents a novel biomolecular phenomenon spanning between folding and binding. It is a structurally independent, short peptide segment within a monomeric protein and fulfills biological function by dynamically binding to/unbinding from its target domain in the same monomer. Here, four representative SBP systems, including mouse proto-oncogene Vav, human retinoic acid receptor RARγ, fruit fly scaffold module INAD and crypto 14-3-3 protein Cp14b, are investigated systematically by using atomistic molecular dynamics (MD) simulations and post binding energetics analyses. The native bound structure, artificial unbound state and isolated peptide segment of SBP moieties in the four systems were constructed, analyzed and compared in detail. It is revealed that the SBP interaction with their targets is almost a binding phenomenon at single-molecule level, but presence of a polypeptide linker between the SBP and target can promote the binding efficiency since the linker restriction largely increases the probability of SBP-target encounters in a statistical physics point of view. In this respect, unlike classical peptide-mediated interactions where the intrinsically disordered peptides are folded into an ordered structure upon binding to their protein partners (folding-upon-binding), we herein propose SBPs as a new and reversed biological event that is naturally a folding phenomenon but exhibits a typical binding behavior (binding-upon-folding).

9.
Curr Drug Metab ; 20(3): 170-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30317994

RESUMO

BACKGROUND: Protein-peptide recognition plays an essential role in the orchestration and regulation of cell signaling networks, which is estimated to be responsible for up to 40% of biological interaction events in the human interactome and has recently been recognized as a new and attractive druggable target for drug development and disease intervention. METHODS: We present a systematic review on the application of machine learning techniques in the quantitative modeling and prediction of protein-peptide binding affinity, particularly focusing on its implications for therapeutic peptide design. We also briefly introduce the physical quantities used to characterize protein-peptide affinity and attempt to extend the content of generalized machine learning methods. RESULTS: Existing issues and future perspective on the statistical modeling and regression prediction of protein- peptide binding affinity are discussed. CONCLUSION: There is still a long way to go before establishment of general, reliable and efficient machine leaningbased protein-peptide affinity predictors.


Assuntos
Aprendizado de Máquina , Peptídeos/metabolismo , Proteínas/metabolismo , Desenho de Drogas , Humanos , Modelos Moleculares , Peptídeos/uso terapêutico , Ligação Proteica
10.
Chem Sci ; 9(30): 6340-6347, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30310562

RESUMO

Development of molecular probes for the detection of reactive oxygen and nitrogen species (RONS) is important for the pathology and diagnosis of diseases. Although an abnormally high RONS level has been identified in keloids - a benign dermal tumour developed after lesion, the ability of employing RONS probes for keloid detection has not yet been exploited. Herein, we report two near-infrared (NIR) fluorescent probes (CyTF and CyBA) that can specifically distinguish keloid fibroblasts from normal dermal fibroblasts. Both CyTF and CyBA show a 15-fold NIR fluorescence enhancement at 717 nm upon reaction with RONS. However, because CyTF has higher specificity towards ONOO- than CyBA, CyTF can detect stimulated fibroblasts in a more sensitive way, showing 3.76 and 2.26-fold fluorescence increments in TGF-ß1 stimulated dermal fibroblasts and keloid fibroblasts, respectively. Furthermore, CyTF permits specific detection of implanted keloid fibroblasts in a xenograft live mouse model. Our work thus developed a new optical imaging approach that has the potential for early diagnosis and drug screening of keloids.

11.
Adv Mater ; 30(49): e1801778, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30058244

RESUMO

Optical imaging has played a pivotal role in biology and medicine, but it faces challenges of relatively low tissue penetration and poor signal-to-background ratio due to light scattering and tissue autofluorescence. To overcome these issues, second near-infrared fluorescence, self-luminescence, and photoacoustic imaging have recently emerged, which utilize an optical region with reduced light-tissue interactions, eliminate real-time light excitation, and detect acoustic signals with negligible attenuation, respectively. Because there are only a few endogenous molecules absorbing or emitting above the visible region, development of contrast agents is essential for those deep-tissue optical imaging modalities. Organic semiconducting agents with π-conjugated frameworks can be synthesized to meet different optical imaging requirements due to their easy chemical modification and legible structure-property relation. Herein, the deep-tissue optical imaging applications of organic semiconducting agents including small-molecule agents and nanoparticle derivatives are summarized. In particular, the molecular engineering and nanoformulation approaches to further improve the tissue penetration and detection sensitivity of these optical imaging modalities are highlighted. Finally, current challenges and potential opportunities in this emerging subfield of biomedical imaging are discussed.


Assuntos
Fluorescência , Raios Infravermelhos , Imagem Molecular/instrumentação , Compostos Orgânicos , Técnicas Fotoacústicas/instrumentação , Semicondutores , Animais , Humanos , Compostos Orgânicos/metabolismo , Compostos Orgânicos/farmacocinética
12.
Angew Chem Int Ed Engl ; 57(26): 7804-7808, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29665259

RESUMO

Theranostics provides opportunities for precision cancer therapy. However, theranostic probes that simultaneously turn on their diagnostic signal and pharmacological action only in respond to a targeted biomarker have been less exploited. We herein report the synthesis of a macrotheranostic probe that specifically activates its near-infrared fluorescence (NIRF), photoacoustic (PA), and photothermal signals in the presence of a cancer-overexpressed enzyme for imaging-guided cancer therapy. Superior to the small-molecule counterpart probe, the macrotheranostic probe has ideal biodistribution and renal clearance, permitting passive targeting of tumors, in situ activation of multimodal signals, and effective photothermal ablation. Our study thus provides a macromolecular approach towards activatable multimodal phototheranostics.


Assuntos
Diagnóstico por Imagem , Sondas Moleculares/síntese química , Técnicas Fotoacústicas , Fototerapia/métodos , Temperatura Ambiente , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Fluorescência , Xenoenxertos , Humanos , Camundongos , Sondas Moleculares/farmacocinética , Espectrometria de Fluorescência , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
13.
Adv Mater ; 30(21): e1801331, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29611257

RESUMO

Detection of metastatic tumor tissues is crucial for cancer therapy; however, fluorescence agents that allow to do share the disadvantage of low signal-to-background ratio due to tissue autofluorescence. The development of amphiphilic poly(p-phenylenevinylene) derivatives that can self-assemble into the nanoagent (SPPVN) in biological solutions and emit near-infrared afterglow luminescence after cessation of light irradiation for ultrasensitive imaging of metastatic tumors in living mice is herein reported. As compared with the counterpart nanoparticle (PPVP) prepared from the hydrophobic PPV derivate, SPPVN has smaller size, higher energy transfer efficiency, and brighter afterglow luminescence. Moreover, due to the higher PEG density of SPPVN relative to PPVP poly(ethylene glycol), SPPVN has a better accumulation in tumor. Such a high sensitivity and ideal biodistribution allow SPPVN to rapidly detect xenograft tumors with the size as small as 1 mm3 and tiny peritoneal metastatic tumors that are almost invisible to naked eye, which is not possible for PPVP. Moreover, the oxygen-sensitive afterglow makes SPPVN potentially useful for in vivo imaging of oxygen levels. By virtue of enzymatic biodegradability and ideal in vivo clearance, these organic agents can serve as a platform for the construction of advanced afterglow imaging tools.


Assuntos
Nanopartículas , Animais , Luminescência , Camundongos , Neoplasias , Polímeros , Distribuição Tecidual
14.
Angew Chem Int Ed Engl ; 57(15): 3995-3998, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29417709

RESUMO

Regulation of enzyme activity is fundamentally challenging but practically meaningful for biology and medicine. However, noninvasive remote control of enzyme activity in living systems has been rarely demonstrated and exploited for therapy. Herein, we synthesize a semiconducting polymer nanoenzyme with photothermic activity for enhanced cancer therapy. Upon near-infrared (NIR) light irradiation, the activity of the nanoenzyme can be enhanced by 3.5-fold to efficiently digest collagen in the tumor extracellular matrix (ECM), leading to enhanced nanoparticle accumulation in tumors and consequently improved photothermal therapy (PTT). This study thus provides a promising strategy to remotely regulate enzyme activity for cancer therapy.


Assuntos
Raios Infravermelhos , Nanopartículas/química , Polímeros/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , Camundongos , Microscopia Confocal , Nanopartículas/uso terapêutico , Neoplasias/terapia , Imagem Óptica , Fototerapia , Semicondutores , Transplante Heterólogo
15.
Angew Chem Int Ed Engl ; 57(5): 1256-1260, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29316083

RESUMO

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.


Assuntos
Corantes Fluorescentes/química , Queloide/patologia , Linhagem Celular , Gelatinases/genética , Gelatinases/metabolismo , Humanos , Técnicas In Vitro , Queloide/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microscopia de Fluorescência , Modelos Biológicos , Peptídeos/química , Peptídeos/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Pele/metabolismo , Pele/patologia , Espectroscopia de Luz Próxima ao Infravermelho , Especificidade por Substrato
16.
ACS Appl Mater Interfaces ; 9(50): 44199-44213, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29185333

RESUMO

A simple in situ self-assembly selective synthetic strategy for one-step controllable formation of various three-dimensional (3D) hierarchical Co3O4 micro/nanomaterials with peculiar morphologies, uniform size, and high quality is successfully developed. The morphological control and related impact factors are investigated and clarified in detail. The results further clarify the corresponding mechanisms on the reaction process, product generation, and calcining process as well as the formation of specific morphologies. Furthermore, the superior catalytic properties of these materials are confirmed by two typical Co-based energy applications on the decomposition of an important solid rocket propellant, ammonium perchlorate (AP), and dye-sensitized solar cells (DSSCs). The addition of Co3O4 materials to AP obviously decreases the decomposition temperatures by about 118-140 °C and increases the exothermic heat to a great extent. As the substituted counter electrodes of DSSCs, the 3D hierarchical Co3O4 materials exhibit attractive photovoltaic performances. These findings provide a facile and effective way for designing new types of 3D hierarchical materials toward high catalytic activity for energy devices.

17.
Nat Biotechnol ; 35(11): 1102-1110, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29035373

RESUMO

Afterglow optical agents, which emit light long after cessation of excitation, hold promise for ultrasensitive in vivo imaging because they eliminate tissue autofluorescence. However, afterglow imaging has been limited by its reliance on inorganic nanoparticles with relatively low brightness and short-near-infrared (NIR) emission. Here we present semiconducting polymer nanoparticles (SPNs) <40 nm in diameter that store photon energy via chemical defects and emit long-NIR afterglow luminescence at 780 nm with a half-life of ∼6 min. In vivo, the afterglow intensity of SPNs is more than 100-fold brighter than that of inorganic afterglow agents, and the signal is detectable through the body of a live mouse. High-contrast lymph node and tumor imaging in living mice is demonstrated with a signal-to-background ratio up to 127-times higher than that obtained by NIR fluorescence imaging. Moreover, we developed an afterglow probe, activated only in the presence of biothiols, for early detection of drug-induced hepatotoxicity in living mice.


Assuntos
Plásticos Biodegradáveis , Luz , Polímeros , Pontos Quânticos/química , Animais , Diagnóstico por Imagem , Células HeLa , Humanos , Substâncias Luminescentes , Camundongos , Camundongos Nus , Neoplasias Experimentais
18.
ACS Nano ; 11(9): 8998-9009, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28841279

RESUMO

Development of optical nanotheranostics for the capability of photodynamic therapy (PDT) provides opportunities for advanced cancer therapy. However, most nanotheranostic systems fail to regulate their generation levels of reactive oxygen species (ROS) according to the disease microenvironment, which can potentially limit their therapeutic selectivity and increase the risk of damage to normal tissues. We herein report the development of hybrid semiconducting polymer nanoparticles (SPNs) with self-regulated near-infrared (NIR) photodynamic properties for optimized cancer therapy. The SPNs comprise a binary component nanostructure: a NIR-absorbing semiconducting polymer acts as the NIR fluorescent PDT agent, while nanoceria serves as the smart intraparticle regular to decrease and increase ROS generation at physiologically neutral and pathologically acidic environments, respectively. As compared with nondoped SPNs, the NIR fluorescence imaging ability of nanoceria-doped SPNs is similar due to the optically inactive nature of nanoceria; however, the self-regulated photodynamic properties of nanoceria-doped SPN not only result in dramatically reduced nonspecific damage to normal tissue under NIR laser irradiation but also lead to significantly enhanced photodynamic efficacy for cancer therapy in a murine mouse model. This study thus provides a simple yet effective hybrid approach to modulate the phototherapeutic performance of organic photosensitizers.


Assuntos
Cério/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Pontos Quânticos/uso terapêutico , Animais , Cério/química , Corantes Fluorescentes/química , Depuradores de Radicais Livres/química , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Polímeros/química , Pontos Quânticos/química , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica/métodos
19.
Bioconjug Chem ; 27(12): 2808-2823, 2016 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-27998078

RESUMO

Photoacoustic (PA) imaging as a new hybrid imaging modality holds great promise for real-time in vivo monitoring of biological processes with deep tissue penetration and high spatial resolution. To endow PA imaging with the ability to provide real-time molecular information at disease sites, molecular probes that can change their PA signals responding to the target or event of interest have to be developed. This review focuses on the recent development of smart activatable PA probes for molecular imaging. A brief summary of PA imaging agents is given first, followed by the detailed discussion of the contemporary design approaches toward activatable PA probes for different imaging applications. At last, the current challenges are highlighted.


Assuntos
Imagem Molecular/métodos , Técnicas Fotoacústicas/métodos , Animais , Enzimas/química , Furina/química , Humanos , Concentração de Íons de Hidrogênio , Metaloproteinases da Matriz/química , Metais/química , Sondas Moleculares/química , Sondas Moleculares/classificação , Espécies Reativas de Oxigênio , Temperatura Ambiente
20.
ACS Nano ; 10(6): 6400-9, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27299477

RESUMO

Detection of reactive oxygen species (ROS), a hallmark of many pathological processes, is imperative to understanding, detection and treatment of many life-threatening diseases. However, methods capable of real-time in situ imaging of ROS in living animals are still very limited. We herein report the development and optimization of chemiluminescent semiconducting polymer nanoparticles (SPNs) for ultrasensitive in vivo imaging of hydrogen peroxide (H2O2). The chemiluminescence is amplified by adjusting the energy levels between the luminescence reporter and the chemiluminescence substrate to facilitate intermolecular electron transfer in the process of H2O2-activated luminescence. The optimized SPN can emit chemiluminescence with the quantum yield up to 2.30 × 10(-2) einsteins/mol and detect H2O2 down to 5 nM, which substantially outperforms the previous probes. Further doping of this SPN with a naphthalocyanine dye creates intraparticle chemiluminescence resonance energy transfer (CRET), leading to the near-infrared (NIR) luminescence responding to H2O2. By virtue of high brightness and ideal NIR optical window, SPN-NIR permits ultrasensitive imaging of H2O2 in the mouse models of peritonitis and neuroinflammation with the minute administration quantity. Thus, this study not only provides a category of optical probes that eliminates the need of external light excitation for imaging of H2O2, but also reveals the underlying principle to enhance the brightness of chemiluminescence systems.


Assuntos
Luminescência , Nanopartículas , Polímeros , Espécies Reativas de Oxigênio , Animais , Peróxido de Hidrogênio , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA