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1.
Science ; 373(6552): 337-342, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34437153

RESUMO

Piezoelectric biomaterials are intrinsically suitable for coupling mechanical and electrical energy in biological systems to achieve in vivo real-time sensing, actuation, and electricity generation. However, the inability to synthesize and align the piezoelectric phase at a large scale remains a roadblock toward practical applications. We present a wafer-scale approach to creating piezoelectric biomaterial thin films based on γ-glycine crystals. The thin film has a sandwich structure, where a crystalline glycine layer self-assembles and automatically aligns between two polyvinyl alcohol (PVA) thin films. The heterostructured glycine-PVA films exhibit piezoelectric coefficients of 5.3 picocoulombs per newton or 157.5 × 10-3 volt meters per newton and nearly an order of magnitude enhancement of the mechanical flexibility compared with pure glycine crystals. With its natural compatibility and degradability in physiological environments, glycine-PVA films may enable the development of transient implantable electromechanical devices.


Assuntos
Materiais Biocompatíveis/química , Eletricidade , Glicina/química , Álcool de Polivinil/química , Animais , Sobrevivência Celular , Células Cultivadas , Cristalização , Teoria da Densidade Funcional , Elasticidade , Humanos , Ligação de Hidrogênio , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Estresse Mecânico
2.
Nano Lett ; 21(11): 4692-4699, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34029471

RESUMO

Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair 90/86Y, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with 86Y-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 ± 1.7 and 1.5 ± 0.5, respectively), unprecedented for inorganic nanomaterials. 90Y-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Porosidade , Medicina de Precisão , Dióxido de Silício
3.
J Nanobiotechnology ; 19(1): 107, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858424

RESUMO

BACKGROUND: Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials' propensity for liver distribution might enable their use in hepatic ischemia-reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. RESULTS: To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. CONCLUSIONS: The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.


Assuntos
Antioxidantes/metabolismo , Antioxidantes/farmacologia , Complemento C5a/metabolismo , Fígado/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Animais , Cério , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/farmacologia , Isquemia , Fígado/patologia , Camundongos , Nanomedicina , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia
4.
Adv Healthc Mater ; 10(5): e2000690, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32691969

RESUMO

Advances in technology and nanomedicine have led to the development of nanoparticles that can be activated for multimodal imaging of cancer, where a stimulus induces a material modification that enhances image contrast. Multimodal imaging using nanomaterials with this capability can combine the advantages and overcome the limitations of any single imaging modality. When designed with stimuli-responsive abilities, the target-to-background ratio of multimodal imaging nanoprobes increases because specific stimuli in the tumor enhance the signal. Several aspects of the tumor microenvironment can be exploited as an internal stimulus response for multimodal imaging applications, such as the pH gradient, redox processes, overproduction of various enzymes, or combinations of these. In this review, design strategies are discussed and an overview of the recent developments of internally responsive multimodal nanomaterials is provided. Properly implementing this approach improves noninvasive cancer diagnosis and staging as well as provides a method to monitor drug delivery and treatment response.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Imagem Multimodal , Nanomedicina , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
5.
J Nanobiotechnology ; 18(1): 141, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008409

RESUMO

As a main element in the hard metal industry, cobalt is one of the major components of human metal implants. Cobalt-containing implants, especially joint prostheses used for artificial joint replacement, can be corroded due to the complex physiological environment in vivo, producing a large number of nanoscale cobalt particles (Cobalt Nanoparticles, CoNPs). These CoNPs can be first accumulated around the implant to cause adverse local reactions and then enter into the blood vessels followed by reaching the liver, heart, brain, kidney, and other organs through systematic circulation, which leads to multi-system toxicity symptoms. To ensure the long-term existence of cobalt-containing implants in the body, it is urgently required to find out a safe and effective detoxification drug. Herein, we have demonstrated that CoNPs could induce the ferroptosis-like cell death through the enhancement of intracellular reactive oxygen species (ROS) level, cytoplasmic Fe2+ level, lipid peroxidation, and consumption of reduced glutathione (GSH) as well as inhibition of glutathione peroxidase 4 (GPX4) activity. Importantly, α-lipoic acid (ALA), a natural antioxidant with the capability to scavenge free radicals and chelate toxic metals, was found to efficiently alleviate the adverse effects of CoNPs. The present study illustrates a new mechanism of CoNPs mediated by ferroptosis-like cytotoxicity and discloses an effective method for the detoxification of CoNPs by employing the natural antioxidant of ALA, providing a basis for further in vivo detoxification study.

6.
Front Chem ; 8: 804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33094098

RESUMO

Interest in cancer immunotherapy has rapidly risen since it offers many advantages over traditional approaches, such as high efficiency and prevention of metastasis. Efforts have primarily focused on two major strategies for regulating the body's antitumor immune response mechanisms: "enhanced immunotherapy" that aims to amplify the immune activation, and "normalized immunotherapy" that corrects the defective immune mechanism in the tumor immune microenvironments (TIMEs), which returns to the normal immune trajectory. However, due to the complexity and heterogeneity of the TIMEs, and lack of visualization research on the immunotherapy process, cancer immunotherapy has not been widely used in clinical setting. Recently, through the design and modification of nanomaterials, intelligent TIME-responsive nanoplatforms were developed from which encouraging results in many aspects of immunotherapy have been achieved. In this mini review, the status of designed nanomaterials for nanoplatform-based immune regulation of TIMEs has been emphasized, particularly with respect to the aforementioned approaches. It is envisaged that future prospects will focus on a combination of multiple immunotherapies for more efficient cancer inhibition and elimination.

7.
Acc Chem Res ; 53(9): 1869-1880, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32786331

RESUMO

Nanomedicine has benefited from recent advances in chemistry and biomedical engineering to produce nanoscale materials as theranostic agents. Well-designed nanomaterials may present optimal biological properties, influencing circulation, retention, and excretion for imaging and treatment of various diseases. As the understanding of nanomedicine pharmacokinetics expands continuously, efficient renal clearance of nanomedicines can significantly increase the signal-to-background ratio for precision diagnosis and lower potential toxicity for improved treatment. Studies on nanomaterial-kidney interactions have led to many novel findings on the underlying principles of nanomaterial renal clearance, targeting, and accumulation. In return, the optimized nanomedicines confer significant benefits to the detection and treatment of kidney dysfunction.In this Account, we present an overview of recent progress in the development of nanomaterials for kidney theranostics, aiming to speed up translation and expand possible applications. We start by introducing biological structures of the kidney and their influence on renal targeting, retention, and clearance. Several key factors regarding renal accumulation and excretion, including nanomaterial types, sizes, and shapes, surface charges, and chemical modifications, are identified and discussed. Next, we highlight our recent efforts investigating kidney-interacting nanomaterials and introduce representative nanomedicines for imaging and treatment of kidney diseases. Multiple renal-clearable and renal-accumulating nanomedicines were devised for kidney function imaging. By employing renal-clearable nanomedicines, including gold nanoparticles, porphyrin polymers, DNA frameworks, and polyoxometalate clusters, we were able to noninvasively evaluate split renal function in healthy and diseased mice. Further engineering of renal-accumulating nanosystems has shifted attention from renal diagnosis to precision kidney protection. Many biocompatible nanomedicines, such as DNA origami, selenium-doped carbon quantum dots, melanin nanoparticles, and black phosphorus have all played essential roles in diminishing excessive reactive oxygen species for kidney treatment and protection. Finally, we discuss the challenges and perspectives of nanomaterials for renal care, their future clinical translation, and how they may affect the current landscape of clinical practices. We believe that this Account updates our current understanding of nanomaterial-kidney interactions for further design and control of nanomedicines for specific kidney diagnosis and treatment. This timely Account will generate broad interest in integrating nanotechnology and nanomaterial-biological interaction for state-of-the-art theranostics of renal diseases.


Assuntos
Nefropatias/prevenção & controle , Nanomedicina , Nanoestruturas/química , Animais , Materiais Biocompatíveis/química , Meios de Contraste/química , DNA/química , Taxa de Filtração Glomerular , Glucocorticoides/uso terapêutico , Ouro/química , Rim/diagnóstico por imagem , Rim/fisiologia , Nefropatias/diagnóstico por imagem , Nefropatias/tratamento farmacológico , Imageamento por Ressonância Magnética , Nanopartículas Metálicas/química , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
8.
Adv Sci (Weinh) ; 7(13): 2000406, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32670765

RESUMO

Minimizing the interaction of nanomedicines with the mononuclear phagocytic system (MPS) is a critical challenge for their clinical translation. Conjugating polyethylene glycol (PEG) to nanomedicines is regarded as an effective approach to reducing the sequestration of nanomedicines by the MPS. However, recent concerns about the immunogenicity of PEG highlight the demand of alternative low-fouling polymers as innovative coating materials for nanoparticles. Herein, a highly hydrophilic sulfoxide-containing polymer-poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA)-is used for the surface coating of iron oxide nanoparticles (IONPs). It is found that the PMSEA polymer coated IONPs have a more hydrophilic surface than their PEGylated counterparts, and demonstrate remarkably reduced macrophage cellular uptake and much less association with human plasma proteins. In vivo study of biodistribution and pharmacokinetics further reveals a much-extended blood circulation (≈2.5 times longer in terms of elimination half-life t 1/2) and reduced accumulation (approximately two times less) in the organs such as the liver and spleen for IONPs coated by PMSEA than those by PEG. It is envisaged that the highly hydrophilic sulfoxide-containing polymers have huge potential to be employed as an advantageous alternative to PEG for the surface functionalization of a variety of nanoparticles for long circulation and improved delivery.

9.
Small ; 16(23): e1907233, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32406198

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors with extremely poor prognosis due to the later stage diagnosis when surgical resection is no longer applicable. Alternatively, the traditional gene therapy which drives pancreatic cancer cells into an inactive state and inhibiting the proliferation and metastasis, presents potentials to safely inhibit pancreatic cancer progression, but unfortunately has received limited success to date. Here, an efficient gene therapy of pancreatic cancer is shown via a peptide nucleic acid (PNA)-loaded layered double hydroxides (LDHs) nanoplatform. Compared with the traditional DNA- or RNA-based gene therapies, the gene therapy using PNA features great advantages in recognizing and hybridizing with the target mutant sequences to form PNA-DNA hybrids with significantly enhanced stability due to the absence of electrostatic repulsion, and the constrained flexibility of the polyamide backbone. Moreover, ultrasmall LDHs are engineered to load PNA and the obtained PNA-loaded LDH platform (LDHs/PNA) is capable of efficiently and selectively targeting the intranuclear mutant sequences thanks to the proton sponge effect. Treatments with LDHs/PNA demonstrate markedly inhibited growth of pancreatic cancer xenografts via a cancer cell proliferation suppression mechanism. The results demonstrate the great potentials of LDHs/PNA as a highly promising gene therapy agent for PDAC.


Assuntos
Neoplasias Pancreáticas , Ácidos Nucleicos Peptídicos , Terapia Genética , Humanos , Hidróxidos , Neoplasias Pancreáticas/terapia , RNA
10.
Mol Pharm ; 17(5): 1697-1705, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32202792

RESUMO

Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair 86/90Y as a theranostic agent against pancreatic cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of 86Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tromboplastina/antagonistas & inibidores , Radioisótopos de Ítrio/farmacocinética , Animais , Anticorpos Monoclonais/farmacocinética , Linhagem Celular Tumoral , Feminino , Camundongos , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Distribuição Tecidual
11.
Adv Sci (Weinh) ; 7(4): 1902600, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32076591

RESUMO

Intrathecal injection, drugs transporting along perivascular spaces, represents an important route for maintaining blood-brain barrier (BBB) integrity after cerebral ischemia/reperfusion (I/R) injury. However, after being directly injected into cerebrospinal fluid (CSF), the temporal and spatial changes in the distribution of therapeutic protein drugs have remained unknown. Here, with positron emission tomography (PET) imaging, the uptake of 89Zr-agrin is noninvasively and dynamically monitored. These data demonstrate the time-activity curve of drugs in the brain subregions and their spatial distribution in different organs after intrathecal administration. Furthermore, agrin treatment effectively inhibits BBB disruption by reducing the loss of tight-junctional proteins. Importantly, the infarct volume is reduced; the number of apoptotic neurons is decreased; and neurological function is improved in mouse I/R injury models. Thus, intrathecal injection of agrin provides the basis for a new strategy to research and develop protein drugs for reducing the aggravation of I/R injury.

12.
ACS Nano ; 14(1): 1033-1044, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31935064

RESUMO

Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe2O4@MnFe2O4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.


Assuntos
Neoplasias da Mama/terapia , Cobalto/farmacologia , Compostos Férricos/farmacologia , Hipertermia Induzida , Imunoterapia , Compostos de Manganês/farmacologia , Animais , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobalto/química , Feminino , Compostos Férricos/química , Humanos , Fenômenos Magnéticos , Compostos de Manganês/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Tamanho da Partícula , Propriedades de Superfície
13.
Adv Mater ; 32(4): e1904011, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793717

RESUMO

Biodegradable nanoprodrugs, inheriting the antitumor effects of chemotherapy drugs and overcoming the inevitable drawback of side effects on normal tissues, hold promise as next-generation cancer therapy candidates. Biodegradable nanoprodrugs of transferrin-modified MgO2 nanosheets are developed to selectively deliver reactive oxygen species to cancer cells for molecular dynamic therapy strategy. The nanosheets favor the acidic and low catalase activity tumor microenvironment to react with proton and release nontoxic Mg2+ . This reaction simultaneously produces abundant H2 O2 to induce cell death and damage the structure of transferrin to release Fe3+ , which will react with H2 O2 to produce highly toxic ·OH to kill tumor cells.


Assuntos
Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/uso terapêutico , Peróxido de Hidrogênio/toxicidade , Óxido de Magnésio/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pró-Fármacos/metabolismo , Pró-Fármacos/uso terapêutico , Pró-Fármacos/toxicidade , Espécies Reativas de Oxigênio/uso terapêutico , Espécies Reativas de Oxigênio/toxicidade , Transferrinas/química
14.
J Nanobiotechnology ; 17(1): 123, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847857

RESUMO

BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.


Assuntos
Acrilamidas/síntese química , Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/química , Nanocápsulas/química , Polímeros/síntese química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Camundongos Nus , Imagem Óptica/métodos , Distribuição Tecidual
15.
Adv Mater ; 31(52): e1904894, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31709622

RESUMO

Cerenkov radiation (CR) from radionuclides can act as a built-in light source for cancer theranostics, opening a new horizon in biomedical applications. However, considerably low tumor-targeting efficiency of existing radionuclides and radionuclide-based nanomedicines limits the efficacy of CR-induced theranostics (CRIT). It remains a challenge to precisely and efficiently supply CR energy to the tumor site. Here, a "missile-detonation" strategy is reported, in which a high dose of p-SCN-Bn-deferoxamine-porphyrin-PEG nanocomplex (Df-PPN) is first adminstered as a CR energy receiver/missile to passively target to tumor, and then a low dose of the 89 Zr-labeled Df-PPN is administrated as a CR energy donor/detonator, which can be visualized and quantified by Cerenkov energy transfer imaging, positron-emission tomography, and fluorescence imaging. Based on homologous properties, the colocalization of Df-PPN and 89 Zr-Df-PPN in the tumor site is maximized and efficient CR energy transfer is enabled, which maximizes the tumor-targeted CRIT efficacy in an optimal spatiotemporal setting while also reducing adverse off-target effects from CRIT. This precise and efficient CRIT strategy causes significant tumor vascular damage and inhibited tumor growth.


Assuntos
Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Desferroxamina/química , Transferência de Energia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Neoplasias/irrigação sanguínea , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Estresse Oxidativo/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polietilenoglicóis/química , Porfirinas/química , Tomografia por Emissão de Pósitrons , Radioisótopos/química , Distribuição Tecidual , Transplante Heterólogo , Zircônio/química
16.
Adv Sci (Weinh) ; 6(22): 1901724, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763153

RESUMO

Hydrogen sulfide (H2S) is of vital importance in several biological and physical processes. The significance of H2S-specific detection and monitoring is emphasized by its elevated levels in various diseases such as cancer. Nanotechnology enhances the performance of chemical sensing nanoprobes due to the enhanced efficiency and sensitivity. Recently, extensive research efforts have been dedicated to developing novel smart H2S-triggered/therapeutic system (SHTS) nanoplatforms for H2S-activated sensing, imaging, and therapy. Herein, the latest SHTS-based nanomaterials are summarized and discussed in detail. In addition, therapeutic strategies mediated by endogenous H2S as a trigger or exogenous H2S delivery are also included. A comprehensive understanding of the current status of SHTS-based strategies will greatly facilitate innovation in this field. Lastly, the challenges and key issues related to the design and development of SHTS-based nanomaterials (e.g., morphology, surface modification, therapeutic strategies, appropriate application, and selection of nanomaterials) are outlined.

17.
ACS Nano ; 13(11): 13382-13389, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31603304

RESUMO

Oxidative stress is one of the important mechanisms in cerebral ischemia/reperfusion (I/R) injury. Antioxidants with high brain accumulation are highly desired to help prevent cerebral I/R injury. Herein, intrathecal injection of polyoxometalate (POM) nanoclusters as nano-antioxidants with preferential brain uptake were applied for neuronal protection in cerebral I/R injury. Using powerful positron emission tomography imaging, the uptake of nano-antioxidants in the brain was non-invasively and real-timely monitored. Our results demonstrated that POM nanoclusters rapidly reached the ischemic penumbra after intrathecal injection and effectively scavenged reactive oxygen species (ROS) for inhibiting oxidative stress. The infarct size was reduced, and neurological function was restored in cerebral I/R injury rat models. As a proof-of-concept, the intrathecal injection of nano-antioxidants is an excellent therapeutic strategy to ameliorate cerebral I/R injury.


Assuntos
Antioxidantes/farmacologia , Isquemia Encefálica/tratamento farmacológico , Nanopartículas/química , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Compostos de Tungstênio/farmacologia , Animais , Antioxidantes/administração & dosagem , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Injeções Espinhais , Imageamento por Ressonância Magnética , Nanopartículas/administração & dosagem , Neurônios/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Compostos de Tungstênio/administração & dosagem
18.
Nano Lett ; 19(10): 7334-7341, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518140

RESUMO

Effective therapy for protecting dying neurons against cerebral ischemia-reperfusion injury (IRI) represents a substantial challenge in the treatment of ischemic strokes. Oxidative stress coupled with excessive inflammation is the main culprit for brain IRI that results in neuronal damage and disability. Specifically, complement component 5a (C5a) exacerbates the vicious cycle between oxidative stress and inflammatory responses. Herein, we propose that a framework nucleic acid (FNA) conjugated with anti-C5a aptamers (aC5a) can selectively reduce C5a-mediated neurotoxicity and effectively alleviate oxidative stress in the brain. Intrathecal injection of the aC5a-conjugated FNA (aC5a-FNA) was applied for the treatment of rats with ischemic strokes. Positron emission tomography (PET) imaging was performed to investigate the accumulation of aC5a-FNA in the penumbra and its therapeutic efficacy. Results demonstrated that aC5a-FNA could rapidly penetrate different brain regions after brain IRI. Furthermore, aC5a-FNA effectively protected neurons from brain IRI, as verified by serum tests, tissue staining, biomarker detection, and functional assessment. The protective effect of aC5a-FNA against cerebral IRI in living animals may pave the way for the translation of FNA from bench to bedside and broaden the horizon of FNA in the field of biomedicine.


Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Complemento C5a/antagonistas & inibidores , Ácidos Nucleicos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Aptâmeros de Nucleotídeos/administração & dosagem , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Complemento C5a/imunologia , Injeções Espinhais , Ácidos Nucleicos/administração & dosagem , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia
19.
Adv Mater ; 31(40): e1902956, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418951

RESUMO

The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a "blackbox" by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)-related disease. Ceria nanoparticles (NPs) are selected as a representative nano-antioxidant and the detailed mechanism of preventing IRI is investigated. It is found that ceria NPs effectively alleviate the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines are then significantly reduced and the recruitment and infiltration of neutrophils are minimized, which suppress subsequent inflammatory reaction involved in the liver. The protective effect of nano-antioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.


Assuntos
Cério/química , Cério/farmacologia , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Nanomedicina , Nanopartículas/química , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Cério/farmacocinética , Citocinas/metabolismo , Fígado/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Distribuição Tecidual
20.
Chem Soc Rev ; 48(14): 3683-3704, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31119258

RESUMO

Nanozymes are nanomaterial-based artificial enzymes. By effectively mimicking catalytic sites of natural enzymes or harboring multivalent elements for reactions, nanozyme systems have successfully served as direct surrogates of traditional enzymes for catalysis. With the rapid development and ever-deepening understanding of nanotechnology, nanozymes offer higher catalytic stability, ease of modification and lower manufacturing cost than protein enzymes. Additionally, nanozymes possess inherent nanomaterial properties, providing not only a simple substitute of enzymes but also a multimodal platform interfacing complex biologic environments. Recent extensive research has focused on designing various nanozyme systems that are responsive to one or multiple substrates by tailored means. Catalytic activities of nanozymes can be regulated by pH, H2O2 and glutathione concentrations and levels of oxygenation in different microenvironments. Moreover, nanozymes can be remotely-controlled via different stimuli, including a magnetic field, light, ultrasound, and heat. Collectively, these factors can be adjusted to maximize the diagnostic and therapeutic efficacies of different diseases in biomedical settings. Therefore, by integrating the catalytic property and inherent nanomaterial nature of nanozyme systems, we anticipate that stimuli-responsive nanozymes will open up new horizons for diagnosis, treatment, and theranostics.


Assuntos
Tecnologia Biomédica , Nanoestruturas/química , Animais , Humanos
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