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1.
Small ; 15(16): e1900691, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30913380

RESUMEN

Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.


Asunto(s)
Portadores de Fármacos , Fulerenos/química , Gadolinio/química , Imagen por Resonancia Magnética , Animales , Medios de Contraste/química , Preparaciones de Acción Retardada/uso terapéutico , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Microambiente Tumoral
2.
Small ; 15(41): e1903422, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31448577

RESUMEN

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.


Asunto(s)
Gadolinio/química , Imagen por Resonancia Magnética , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Tamaño de la Partícula , Resinas Acrílicas/química , Línea Celular Tumoral , Humanos , Nanopartículas/ultraestructura
3.
Angew Chem Int Ed Engl ; 57(28): 8463-8467, 2018 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-29757483

RESUMEN

The approach of concurrent-to-synchronous chemoradiation has now been advanced by well-designed nanovesicles that permit X-ray irradiation-triggered instant drug release. The nanovesicles consist of Au nanoparticles tethered with irradiation labile linoleic acid hydroperoxide (LAHP) molecules and oxidation-responsive poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) polymers, where DOX were loaded in the inner core of the vesicles (Au-LAHP-vDOX). Upon irradiation, the in situ formation of hydroxyl radicals from LAHP molecules triggers the internal oxidation of PPS from being hydrophobic to hydrophilic, leading to degradation of the vesicles and burst release of cargo drugs. In this manner, synchronous chemoradiation showed impressive anticancer efficacy both in vitro and in a subcutaneous mouse tumor model by one-dose injection and one-time irradiation.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos/efectos de la radiación , Oro/química , Nanopartículas/química , Rayos X , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ácidos Linoleicos/química , Peróxidos Lipídicos/química , Ratones , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Tamaño de la Partícula , Polímeros/química , Tomografía de Emisión de Positrones , Propiedades de Superficie
4.
Angew Chem Int Ed Engl ; 57(43): 14101-14105, 2018 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-30199138

RESUMEN

Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.


Asunto(s)
Glutatión/química , Neoplasias/terapia , Fototerapia/métodos , Polímeros/química , Semiconductores , Nanomedicina Teranóstica , Compuestos de Tungsteno/química , Humanos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Polimerizacion , Espectroscopía Infrarroja Corta , Microambiente Tumoral
5.
J Am Chem Soc ; 139(44): 15940-15949, 2017 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-29019660

RESUMEN

Despite the well-known anticancer activity of mono- and multinuclear platinum complexes, studies of the antitumor performances of platinum-based supramolecular coordination complexes are rare. Herein, we report on the synthesis of a four-armed amphiphilic copolymer, Pt-PAZMB-b-POEGMA, containing a metallacycle M, in which the tetraphenylethene derivative acts as an aggregation-induced emissive fluorescent probe for live cell imaging and the 3,6-bis[trans-Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further self-assembled into nanoparticles of different sizes and vesicles depending upon the experimental conditions. The impacts of the morphology and size of the assemblies on their endocytic pathways, uptake rates, internalization amounts, and cytotoxicities were investigated. The self-assemblies were further employed to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect. Controlled drug release was also realized via amphiphilicity changes and was driven by a glutathione-induced cascade elimination reaction. The DOX-loaded nanoparticles of around 50 nm in size exhibited an excellent antitumor performance as well as a low systemic toxicity, due to an enhanced permeability and retention effect.


Asunto(s)
Antineoplásicos/farmacología , Colorantes Fluorescentes/química , Polímeros/química , Polímeros/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/química , Liberación de Fármacos , Sinergismo Farmacológico , Endocitosis , Glutatión , Células HeLa , Humanos , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/efectos adversos , Nanopartículas/química , Polímeros/administración & dosificación , Polímeros/efectos adversos , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Vet Radiol Ultrasound ; 58(5): 607-612, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28699200

RESUMEN

Insulinoma is a functional, insulin-secreting tumor, arising from the beta islet cells of the pancreas. It is one of the most common neoplasms in ferrets and has been associated with clinical signs of hypoglycemia, such as ptyalism, pawing at the mouth, seizures, lethargy, and coma. The ultrasonographic features of insulinoma in ferrets have not been previously reported. The purpose of this retrospective case series study was to describe the ultrasonographic features of confirmed insulinoma in a group of ferrets. Inclusion criteria were abdominal ultrasound examination and histological confirmed insulinoma by surgical biopsy. Six ferrets met the inclusion criteria, all of which had multiple hypoglycemic episodes. Ultrasonographic images were reviewed and the characteristics of the pancreatic nodules were recorded. Twenty-eight pancreatic nodules were observed in the six ferrets and were primarily hypoechoic (89.3%, 25/28) and homogenous (46.4%, 13/28) with a smooth margin (78.6%, 22/28). The distribution of the pancreatic nodules was 46.4% in the left lobe, 50% in the right lobe, and 3.6% in the body of the pancreas. The sizes of the pancreatic nodules varied from 1.5 × 1.5 to 4.1 × 5.6 mm. All of the pancreatic nodules removed from surgery were histopathologically confirmed as insulinoma. The findings indicated that insulinoma in ferrets could be detected through ultrasonography, which may facilitate diagnosis and preoperative surgical planning.


Asunto(s)
Hurones , Insulinoma/veterinaria , Neoplasias Pancreáticas/veterinaria , Animales , Femenino , Insulinoma/diagnóstico por imagen , Masculino , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Retrospectivos
7.
Angew Chem Int Ed Engl ; 56(28): 8110-8114, 2017 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-28557263

RESUMEN

Janus nanoparticles (JNPs) offer unique features, including the precisely controlled distribution of compositions, surface charges, dipole moments, modular and combined functionalities, which enable excellent applications that are unavailable to their symmetrical counterparts. Assemblies of NPs exhibit coupled optical, electronic and magnetic properties that are different from single NPs. Herein, we report a new class of double-layered plasmonic-magnetic vesicle assembled from Janus amphiphilic Au-Fe3 O4 NPs grafted with polymer brushes of different hydrophilicity on Au and Fe3 O4 surfaces separately. Like liposomes, the vesicle shell is composed of two layers of Au-Fe3 O4 NPs in opposite direction, and the orientation of Au or Fe3 O4 in the shell can be well controlled by exploiting the amphiphilic property of the two types of polymers.


Asunto(s)
Compuestos Férricos/química , Oro/química , Magnetismo , Nanopartículas del Metal/química , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Polímeros/química , Espectroscopía de Protones por Resonancia Magnética , Espectrometría Raman , Resonancia por Plasmón de Superficie , Propiedades de Superficie , Termodinámica
8.
Angew Chem Int Ed Engl ; 55(49): 15297-15300, 2016 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-27862808

RESUMEN

Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T2 ) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2-3 times in the PA and MR imaging, compared with control groups without a magnetic field.


Asunto(s)
Oro/química , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Neoplasias/diagnóstico por imagen , Animales , Humanos , Campos Magnéticos , Tamaño de la Partícula , Procesos Fotoquímicos , Polietilenglicoles/química , Poliestirenos/química
9.
Cell Transplant ; 32: 9636897221148775, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36661068

RESUMEN

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease associated with impaired organ functions that can seriously affect the daily life of patients. Recent SLE therapies frequently elicit adverse reactions and side effects in patients, and clinical heterogeneity is considerable. Mesenchymal stromal cells (MSCs) have anti-inflammatory, tissue repair, and immunomodulatory properties. Their ability to treat autoimmune diseases largely depends on secreted extracellular vesicles, especially exosomes. The effects of exosomes and microRNAs (miRNAs) on SLE have recently attracted interest. This review summarizes the applications of MSCs derived from bone marrow, adipocyte tissue, umbilical cord, synovial membrane, and gingival tissue, as well as exosomes to treating SLE and the key roles of miRNAs. The efficacy of MSCs infusion in SLE patients with impaired autologous MSCs are reviewed, and the potential of exosomes and their contents as drug delivery vectors for treating SLE and other autoimmune diseases in the future are briefly described.


Asunto(s)
Exosomas , Lupus Eritematoso Sistémico , Células Madre Mesenquimatosas , MicroARNs , Humanos , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Exosomas/genética , Exosomas/inmunología , Vesículas Extracelulares/genética , Vesículas Extracelulares/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/terapia , MicroARNs/genética , MicroARNs/inmunología , Células Madre Mesenquimatosas/inmunología
10.
Materials (Basel) ; 16(13)2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37445119

RESUMEN

Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery.

11.
Adv Healthc Mater ; 12(31): e2302314, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37714523

RESUMEN

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug-loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively-charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long-term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)-loaded cationic liposomes-integrated MNs show better therapeutic outcomes than dex-loaded anionic liposomes-integrated MNs in a psoriasis-like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation.


Asunto(s)
Liposomas , Psoriasis , Animales , Piel/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Administración Cutánea , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Agujas
12.
J Am Chem Soc ; 134(8): 3639-42, 2012 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-22320198

RESUMEN

Asymmetric multicomponent nanoparticles (AMNPs) offer new opportunities for new-generation materials with improved or new synergetic properties not found in their individual components. There is, however, an urgent need for a synthetic strategy capable of preparing hybrid AMNPs with fine-tuned structural and compositional complexities. Herein, we report a new paradigm for the controllable synthesis of polymer/metal AMNPs with well-controlled size, shape, composition, and morphology by utilizing interfacial polymerization. The hybrid AMNPs display a new level of structural-architectural sophistication, such as controlled domain size and the number of each component of AMNPs. The approach is simple, versatile, cost-effective, and scalable for synthesizing large quantities of AMNPs. Our method may pave a new route to the design and synthesis of advanced breeds of building blocks for functional materials and devices.


Asunto(s)
Nanopartículas/química , Compuestos Organometálicos/síntesis química , Oro/química , Compuestos Organometálicos/química , Tamaño de la Partícula , Polímeros/química , Propiedades de Superficie
13.
Nanoscale ; 12(28): 14957-14975, 2020 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-32648868

RESUMEN

Magnetic iron oxide nanoparticles (IONPs) have wide applications in magnetic resonance imaging (MRI), biomedicine, drug delivery, hyperthermia therapy, catalysis, magnetic separation, and others. However, these applications are usually limited by irreversible agglomeration of IONPs in aqueous media because of their dipole-dipole interactions, and their poor stability. A protecting polymeric shell provides IONPs with not only enhanced long-term stability, but also the functionality of polymer shells. Therefore, polymer-grafted IONPs have recently attracted much attention of scientists. In this tutorial review, we will present the current strategies for grafting polymers onto the surface of IONPs, basically including "grafting from" and "grafting to" methods. Available functional groups and chemical reactions, which could be employed to bind polymers onto the IONP surface, are comprehensively summarized. Moreover, the applications of polymer-grafted IONPs will be briefly discussed. Finally, future challenges and perspectives in the synthesis and application of polymer-grafted IONPs will also be discussed.


Asunto(s)
Nanopartículas , Polímeros , Sistemas de Liberación de Medicamentos , Compuestos Férricos , Nanopartículas Magnéticas de Óxido de Hierro , Magnetismo
14.
Int J Pharm ; 588: 119797, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32828977

RESUMEN

Photodynamic antimicrobial chemotherapy (PACT) has advantages of strong targeting, low resistance to drugs. Electrospinning nanofibers is favorable for wound healing. The combination of PACT and electrospinning nanofibers is appropriate for wound healing, especially infected wound. In our study, indocyanine green (ICG) as photosensitizer had obvious inhibition effects on two antibiotic-resistant bacteria, Methicillin-resistant Staphylococcus aureus (MRSA) and Meropenem-resistant Pseudomonas aeruginosa (MRPA). The optimized electrospinning solution consisted of 2% (w/v) chitosan and 7% (w/v) PVA. The nanofibers observed by scanning electron microscope showed a three-dimensional cross-network with smooth surface, the water absorption ratio of the nanofibers was up to 210%. Fourier transform infrared spectrum and X-ray diffraction showed that the intermolecular hydrogen bonding happened between chitosan and PVA in electrospinning process, which was favorable for the formation of nanofibers. ICG released rapidly from the surface of the nanofibers first and then released continuously. The photodynamic nanofibers could inhibit the bacteria and decreased the F4/80 expression of MRSA-infected rats. The improved effects of wound healing were evaluated with the morphology, wound healing radio, the increased expression of cluster of differentiation 31 (CD31), the decreased level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The photosensitizer-loaded electrospinning nanofibers provide a novel promising option for treatment of infected wound.


Asunto(s)
Quitosano , Staphylococcus aureus Resistente a Meticilina , Nanofibras , Animales , Antibacterianos , Bacterias , Verde de Indocianina , Alcohol Polivinílico , Ratas , Cicatrización de Heridas
15.
Int J Pharm ; 583: 119384, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32371003

RESUMEN

The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188. Its characteristics were evaluated, including rheological properties, drug release in vitro, and mucosal irritation. The pharmacodynamics and brain-targeting effects were also studied. The highly viscous ISGs remained in the nasal cavity for a long time with the sustained release of TET and no obvious ciliary toxicity. Intranasal temperature-sensitive TET ISGs markedly improved the spatial memory and spontaneous exploratory behavior induced by microwave with the Morris water maze (MWM) and the open field test (OFT) compared to the model. The ISGs alleviated the microwave-induced brain damage and inhibited the certain mRNA expressions of calcium channels in the brain. Intranasal temperature-sensitive TET ISGs was rapidly absorbed with a shorter Tmax (4.8 h) compared to that of oral TET (8.4 h). The brain targeting index of intranasal temperature-sensitive TET ISGs was as 2.26 times as that of the oral TET. Intranasal temperature-sensitive TET ISGs are a promising brain-targeted medication for the treatment of microwave-induced brain injury.


Asunto(s)
Bencilisoquinolinas/administración & dosificación , Lesiones Encefálicas/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Canales de Calcio/efectos de los fármacos , Poloxámero/química , Polímeros de Estímulo Receptivo/química , Temperatura , Administración Intranasal , Administración Oral , Animales , Conducta Animal/efectos de los fármacos , Bencilisoquinolinas/química , Bencilisoquinolinas/metabolismo , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Lesiones Encefálicas/etiología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/psicología , Bloqueadores de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/metabolismo , Canales de Calcio/genética , Canales de Calcio/metabolismo , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Composición de Medicamentos , Liberación de Fármacos , Hidrogeles , Masculino , Microondas , Ratas Wistar , Distribución Tisular , Viscosidad
16.
Adv Mater ; 32(11): e1907365, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32022975

RESUMEN

Tumor-lymph node (LN) metastasis is the dominant prognostic factor for tumor staging and therapeutic decision-making. However, concurrently visualizing metastasis and performing imaging-guided lymph node surgery is challenging. Here, a multiplexed-near-infrared-II (NIR-II) in vivo imaging system using nonoverlapping NIR-II probes with markedly suppressed photon scattering and zero-autofluorescence is reported, which enables visualization of the metastatic tumor and the tumor metastatic proximal LNs resection. A bright and tumor-seeking donor-acceptor-donor (D-A-D) dye, IR-FD, is screened for primary/metastatic tumor imaging in the NIR-IIa (1100-1300 nm) window. This optimized D-A-D dye exhibits greatly improved quantum yield of organic D-A-D fluorophores in aqueous solutions (≈6.0%) and good in vivo performance. Ultrabright PbS/CdS core/shell quantum dots (QDs) with dense polymer coating are used to visualize cancer-invaded sentinel LNs in the NIR-IIb (>1500 nm) window. Compared to clinically used indocyanine green, the QDs show superior brightness and photostability (no obvious bleaching even after continuous laser irradiation for 5 h); thus, only a picomolar dose is required for sentinel LNs detection. This combination of dual-NIR-II image-guided surgery can be performed under bright light, adding to its convenience and appeal in clinical use.


Asunto(s)
Colorantes Fluorescentes/química , Metástasis Linfática/diagnóstico por imagen , Imagen Óptica/métodos , Puntos Cuánticos/química , Ganglio Linfático Centinela/diagnóstico por imagen , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Compuestos de Cadmio/química , Línea Celular Tumoral , Femenino , Plomo/química , Metástasis Linfática/terapia , Ratones , Polímeros/química , Compuestos de Selenio/química , Ganglio Linfático Centinela/cirugía , Espectroscopía Infrarroja Corta/métodos , Cirugía Asistida por Computador/métodos
17.
Biomaterials ; 223: 119460, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31513993

RESUMEN

This article describes a nanoplatform based on matrix metalloproteinase (MMP)-responsive gold nanoparticles (AuNPs) for tumor-targeted photoacoustic (PA) imaging-guided photothermal therapy and drug delivery. AuNPs were grafted with complementary DNA strands, tethered with doxorubicin and coated with poly(ethylene glycol) via a thermal-labile linker and a MMP-cleavable peptide, respectively. The nanoprobes remained well-isolated in healthy tissues, but formed aggregates rapidly under MMP-abundant conditions. The DNA hybridization-induced assembly of the nanoprobes led to prolonged tumor retention and strong near-infrared (NIR) absorption, which is beneficial to deep-tissue imaging and therapy. Compared with MMP-inert nanoprobes, our platform demonstrated significantly enhanced efficiency in PA imaging and photothermal conversion upon NIR irradiation. Meanwhile, doxorubicin could be released rapidly in response to the localized elevation of temperature, leading to synergistic chemo-photothermal therapy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to tumors with high specificity, safety, and universality.


Asunto(s)
Oro/química , Metaloproteinasas de la Matriz/química , Nanopartículas del Metal/química , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animales , Línea Celular Tumoral , Medios de Cultivo , ADN/química , Doxorrubicina/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Hipertermia Inducida , Ratones , Nanopartículas/química , Trasplante de Neoplasias , Polietilenglicoles/química , Espectroscopía Infrarroja Corta , Nanomedicina Teranóstica
18.
Nat Commun ; 10(1): 1241, 2019 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-30886142

RESUMEN

The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate •OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of •OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.


Asunto(s)
Antineoplásicos/administración & dosificación , Quimioradioterapia/métodos , Portadores de Fármacos/síntesis química , Liberación de Fármacos/efectos de la radiación , Neoplasias/terapia , Animales , Monóxido de Carbono/química , Femenino , Células Hep G2 , Humanos , Radical Hidroxilo/química , Radical Hidroxilo/efectos de la radiación , Compuestos de Hierro/administración & dosificación , Ratones , Ratones Desnudos , Nanopartículas/química , Compuestos de Organosilicio/síntesis química , Tamaño de la Partícula , Polietilenglicoles/química , Porosidad , Células RAW 264.7 , Resultado del Tratamiento , Rayos X , Ensayos Antitumor por Modelo de Xenoinjerto , terc-Butilhidroperóxido/administración & dosificación , terc-Butilhidroperóxido/efectos de la radiación
19.
Theranostics ; 9(24): 7200-7209, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695762

RESUMEN

Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death. Methods: A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO2 NPs) was presented, which simultaneously delivered exogenous H2O2 and Zn2+ capable of amplifying endogenous ROS production for synergistic cancer therapy. Results: After internalization into tumor cells, ZnO2 NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H2O2 and Zn2+. Intriguingly, Zn2+ could increase the production of mitochondrial O2·- and H2O2 by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H2O2 to promote cancer cell killing. Furthermore, ZnO2 NPs were doped with manganese via cation exchange, making them an activatable magnetic resonance imaging contrast agent. Conclusion: This study establishes a ZnO2-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.


Asunto(s)
Nanopartículas/química , Neoplasias/terapia , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Óxido de Zinc/farmacología , Zinc/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dispersión Dinámica de Luz , Humanos , Concentración de Iones de Hidrógeno , Manganeso/química , Ratones , Nanopartículas/ultraestructura , Povidona , Espectrometría Raman
20.
ACS Appl Mater Interfaces ; 10(34): 28382-28389, 2018 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-30085649

RESUMEN

Accurate diagnosis of tumor is promising to guide photothermal therapy (PTT) for efficacious tumor ablation with minimal damage to healthy tissues. Here, we report an activatable dual-modal imaging agent, which is based on PEGylated-gadolinium metallofullerene-polypyrrole nanoparticle (PEG-GMF-PPy NP) for imaging-guided PTT. A contrast agent (gadolinium metallofullerene, GMF) with excellent magnetic resonance imaging (MRI) performance and an ultra-pH-responsive polymer (PEG-PC7A) are successively modified to the surface of photothermal agent (PPy NP). The prepared PEG-GMF-PPy NPs show strong absorption in the near-infrared (NIR) region, so they can be utilized for photoacoustic imaging. Furthermore, in a tumor extracellular environment, the PEG-GMF-PPy NPs can achieve pH-enhanced MRI because of the hydrophobic-to-hydrophilic conversion of the PC7A. Upon accurate diagnosis-guided NIR laser irradiation, excellent tumor ablation effect is achieved. The results suggest that the PEG-GMF-PPy NPs are promising agents for activatable imaging-guided PTT.


Asunto(s)
Nanopartículas , Gadolinio , Fototerapia , Polímeros , Pirroles
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