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1.
J Am Chem Soc ; 143(19): 7541-7552, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33973784

RESUMO

Phototheranostics constitute an emerging cancer treatment wherein the core diagnostic and therapeutic functions are integrated into a single photosensitizer (PS). Achieving the full potential of this modality requires being able to tune the photosensitizing properties of the PS in question. Structural modification of the organic framework represents a time-honored strategy for tuning the photophysical features of a given PS system. Here we report an easy-to-implement metal selection approach that allows for fine-tuning of excited-state energy dissipation and phototheranostics functions as exemplified by a set of lanthanide (Ln = Gd, Yb, Er) carbazole-containing porphyrinoid complexes. Femto- and nanosecond time-resolved spectroscopic studies, in conjunction with density functional theory calculations, revealed that the energy dissipation pathways for this set of PSs are highly dependent on the energy gap between the lowest triplet excited state of the ligand and the excited states of the coordinated Ln ions. The Yb complex displayed a balance of deactivation mechanisms that made it attractive as a potential combined photoacoustic imaging and photothermal/photodynamic therapy agent. It was encapsulated into mesoporous silica nanoparticles (MSN) to provide a biocompatible construct, YbL@MSN, which displays a high photothermal conversion efficiency (η = 45%) and a decent singlet oxygen quantum yield (ΦΔ = 31%). Mouse model studies revealed that YbL@MSN allows for both photoacoustic imaging and synergistic photothermal- and photodynamic-therapy-based tumor reduction in vivo. Our results lead us to suggest that metal selection represents a promising approach to fine-tuning the excited state properties and functional features of phototheranostics.


Assuntos
Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Nanomedicina Teranóstica , Animais , Elementos da Série dos Lantanídeos/química , Camundongos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química
2.
Mikrochim Acta ; 188(7): 236, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34165637

RESUMO

A turn-on/off ratiometric fluorescence detection platform based on multifunctional lanthanide metal-organic framework (Ln-MOF) and an enzymatic cascade reaction is proposed for alkaline phosphatase (ALP) activity assay. L-phosphotyrosine is hydrolyzed to levodopa (L-dopa) by two steps of enzymatic reaction. L-dopa further reacts with naphthoresorcinol to produce carboxyazamonardine with strong emission at 490 nm. In this process, multifunctional Ln-MOF (Cu@Eu-BTC, BTC is the 1,3,5-benzenetricarboxylic acid) acts not only as a nanozyme to catalyze the fluorogenic reaction between L-dopa and naphthoresorcinol but also as a fluorescence internal standard. The emission of Cu@Eu-BTC at 620 nm is quenched by phosphate anions, and the dual-response ratiometric fluorescence (F490/F620) can be achieved. A good linear relationship was obtained between Δ(F490/F620) and ALP activity in the range 0.3-24 U L-1 with the detection limit of 0.02 U L-1. In addition, a portable assay tube was designed for visual and point-of-care testing of ALP activity by color variation (ratiometric chromaticity). Both the ratiometric fluorescence detection and the visual detection methods were successfully applied to monitor ALP activity in human serum samples with recovery between 95.5%-109.0% and 94.0%-110.1%, and relative standard deviation less than 8.1% and 9.5%, respectively. As far as we know, this is the first report of ALP activity assay assisted by multifunctional Ln-MOF.Graphical abstract.


Assuntos
Fosfatase Alcalina/metabolismo , Elementos da Série dos Lantanídeos/uso terapêutico , Estruturas Metalorgânicas/química , Fluorescência , Humanos , Elementos da Série dos Lantanídeos/farmacologia
3.
Nano Lett ; 19(11): 8234-8244, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31576757

RESUMO

Photosensitizers (PSs) that are directly responsive to X-ray for radiodynamic therapy (RDT) with desirable imaging abilities have great potential applications in cancer therapy. Herein, the cerium (Ce)-doped NaCeF4:Gd,Tb scintillating nanoparticle (ScNP or scintillator) is first reported. Due to the sensitization effect of the Ce ions, Tb ions can emit fluorescence under X-ray irradiation to trigger X-ray excited fluorescence (XEF). Moreover, Ce and Tb ions can absorb the energy of secondary electrons generated by X-ray to produce reactive oxide species (ROS) for RDT. With the intrinsic absorption of X-ray by lanthanide elements, the NaCeF4:Gd,Tb ScNPs also act as a computed tomography (CT) imaging contrast agent and radiosensitizers for radiotherapy (RT) sensitization synchronously. Most importantly, the transverse relaxation time of Gd3+ ions is shortened due to the doping of Ce and Tb ions, leading to the excellent performance of our ScNPs in T2-weighted MR imaging for the first time. Both in vitro and in vivo studies verify that our synthesized ScNPs have good performance in XEF, CT, and T2-weighted MR imaging, and a synchronous RT/RDT is achieved with significant suppression on tumor progression under X-ray irradiation. Importantly, no systemic toxicity is observed after intravenous injection of ScNPs. Our work highlights that ScNPs have potential in multimodal imaging-guided RT/RDT of deep tumors.


Assuntos
Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Células A549 , Animais , Cério/uso terapêutico , Meios de Contraste/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Imagem Óptica , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Tomografia Computadorizada por Raios X , Terapia por Raios X
4.
Nano Lett ; 19(11): 7918-7926, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31645103

RESUMO

Intracellular protein-protein interactions (PPIs) are a vital and yet underexploited class of therapeutic targets for their crucial roles in cellular processes and involvement in disease initiation and progression. Although some successful chemistry and nanotechnologies have been introduced into peptide PPI modulators to allow cell and tissue permeability, significant challenges remain with regard to the efficient and precise modulation of PPIs within specific cells of diseased tissues, such as solid tumors. Herein, an intratumoral transformable hierarchical framework, termed iPLF, was fabricated via a two-step self-assembly between peptides and lanthanide-doped nanocrystals. In this proof-of-concept study, using NanoEL effect, TME response, and tumor marker targeting, iPLF in vivo delivered the p53-MDM2 modulator DPMI into tumor cells and ß-catenin-Bcl9 modulator Bcl9p into tumor stem cells. This crafted programmed nanomedicine with triple-stage delivery and responsiveness accurately modulated the specific intracellular protein-protein interactions, resulting in the suppression of tumor growth and metastasis in vivo, while maintaining a highly favorable safety profile. iPLF reached the goal of accurate, potent, and hazard-free intracellular PPI modulation, thereby providing a means to improve current knowledge of PPI networks and a novel therapeutic strategy for a great variety of diseases.


Assuntos
Antineoplásicos/farmacologia , Elementos da Série dos Lantanídeos/farmacologia , Neoplasias/tratamento farmacológico , Peptídeos/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Preparações de Ação Retardada/química , Desenho de Fármacos , Células HCT116 , Humanos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Camundongos , Nanomedicina , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia , Peptídeos/química , Peptídeos/uso terapêutico , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
5.
Bioconjug Chem ; 29(4): 928-938, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29466856

RESUMO

Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period.


Assuntos
Hipóxia/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Compostos de Manganês/uso terapêutico , Melanoma/tratamento farmacológico , Nanopartículas/uso terapêutico , Óxidos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Ácido Hialurônico/química , Ácido Hialurônico/uso terapêutico , Hipóxia/metabolismo , Hipóxia/patologia , Raios Infravermelhos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Macrófagos/metabolismo , Macrófagos/patologia , Compostos de Manganês/química , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Nanopartículas/química , Óxidos/química , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Células RAW 264.7
6.
Chemistry ; 24(13): 3127-3131, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29243854

RESUMO

The geometric features of two pyclen-based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. The ligand containing two acetate groups and a picolinate arm arranged in a symmetrical fashion (L1) forms a Gd3+ complex being two orders of magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences a much faster dissociation following the acid-catalyzed mechanism than GdL2. On the contrary, GdL1 exhibits a lower exchange rate of the coordinated water molecule compared to GdL2. These very different properties are related to different strengths of the Gd-ligand bonds associated to steric effects, which hinder the coordination of a water molecule in GdL2 and the binding of acetate groups in GdL1.


Assuntos
Elementos da Série dos Lantanídeos/uso terapêutico , Catálise , Meios de Contraste/química , Gadolínio/química , Gadolínio/uso terapêutico , Cinética , Elementos da Série dos Lantanídeos/química , Ligantes , Espectroscopia de Ressonância Magnética , Ácidos Picolínicos/química , Termodinâmica , Água/química
7.
J Labelled Comp Radiopharm ; 61(7): 522-532, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29431234

RESUMO

Since the inception of radiation synovectomy, a host of radioactive colloids and microparticles incorporating suitable therapeutic radionuclides have been proposed for the treatment of arthritis. The present article reports the synthesis and evaluation of barium titanate microparticles as an innovative and effective carrier platform for lanthanide radionuclides in the preparation of therapeutic agents for treatment of arthritis. The material was synthesized by mechanochemical route and characterized by X-ray diffraction, scanning electron microscopy, surface area, and particle size distribution analyses. Loading of lanthanide radionuclides (166 Ho, 153 Sm, 177 Lu, and 169 Er) on the microparticles was achieved in high yield (> 95%) resulting in the formulation of loaded particulates with excellent radiochemical purities (> 99%). Radiolanthanide-loaded microparticles exhibited excellent in vitro stability in human serum. In vitro diethylene triamine pentaacetic acid challenge study indicated fairly strong chemical association of lanthanides with barium titanate microparticles. Long-term biodistribution studies carried out after administration of 177 Lu-loaded microparticles into one of the knee joints of normal Wistar rats revealed near-complete retention of the formulation (> 96% of the administered radioactivity) within the joint cavity even 14 days post-administration. The excellent localization of the loaded microparticles was further confirmed by sequential whole-body radio-luminescence imaging studies carried out using 166 Ho-loaded microparticles.


Assuntos
Artrite/radioterapia , Compostos de Bário/química , Portadores de Fármacos/química , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Microesferas , Titânio/química , Animais , Compostos de Bário/farmacocinética , Fenômenos Químicos , Portadores de Fármacos/farmacocinética , Estabilidade de Medicamentos , Radioquímica , Radioisótopos , Ratos , Ratos Wistar , Distribuição Tecidual , Titânio/farmacocinética
8.
Bioconjug Chem ; 26(2): 166-75, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25254658

RESUMO

Lanthanide-doped photon upconverting nanomaterials are emerging as a new class of imaging contrast agents, providing numerous unprecedented possibilities in the realm of biomedical imaging. Because of their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are able to produce assets of low imaging background, large anti-Stokes shift, as well as high optical penetration depth of light for deep tissue optical imaging or light-activated drug release and therapy. The aim of this review is to line up some issues associated with conventional fluorescent probes, and to address the recent advances of upconverting nanoparticles (UCNPs) as a solution to multiscale biological imaging applications.


Assuntos
Corantes Fluorescentes , Elementos da Série dos Lantanídeos , Nanopartículas , Neoplasias/diagnóstico , Imagem Óptica/métodos , Animais , Corantes Fluorescentes/análise , Corantes Fluorescentes/uso terapêutico , Humanos , Elementos da Série dos Lantanídeos/análise , Elementos da Série dos Lantanídeos/uso terapêutico , Nanopartículas/análise , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos
9.
Angew Chem Int Ed Engl ; 54(27): 7915-9, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26013002

RESUMO

Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great promise in versatile bioapplications. For the first time, organosilica-shelled ß-NaLuF4:Gd/Yb/Er nanoprobes with a rattle structure have been designed for dual-modal imaging and photodynamic therapy (PDT). Benefiting from the unique rattle structure and aromatic framework, these nanoprobes are endowed with a high loading capacity and the disaggregation effect of photosensitizers. After loading of ß-carboxyphthalocyanine zinc or rose Bengal into the nanoprobes, we achieved higher energy transfer efficiency from UCNPs to photosensitizers as compared to those with conventional core-shell structure or with pure-silica shell, which facilitates a large production of singlet oxygen and thus an enhanced PDT efficacy. We demonstrated the use of these nanoprobes in proof-of-concept X-ray computed tomography (CT) and UC imaging, thus revealing the great potential of this multifunctional material as an excellent nanoplatform for cancer theranostics.


Assuntos
Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Técnicas Biossensoriais , Linhagem Celular Tumoral , Humanos , Elementos da Série dos Lantanídeos/química , Luminescência , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Nanopartículas/química , Imagem Óptica , Compostos de Organossilício/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
10.
Adv Healthc Mater ; 12(31): e2302276, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37717206

RESUMO

Ischemic stroke (IS) is one of the most dangerous medical conditions resulting in high mortality and morbidity. The increased brain temperature after IS is closely related to prognosis, making it highly significant for the early diagnosis and the progression evaluation of IS. Herein, a temperature-responsive near infrared (NIR) emissive lanthanide luminescence nanoparticle is developed for the early diagnosis and brain temperature detection of IS. After intravenous injection, the nanoparticles can pass through the damaged blood-brain barrier of the ischemic region, allowing the extravasation and enrichment of nanoparticles into the ischemic brain tissue. The NIR luminescence signals of the nanoparticles are used not only to judge the location and severity of the cerebral ischemic injury but also to report the brain temperature variation in the ischemic area through a visualized way. The results show that the designed nanoparticles can be used for the early diagnosis of ischemic stroke and minimally invasive temperature detection of cerebral ischemic tissues in transient middle cerebral artery occlusion mice model, which is expected to make the clinical diagnosis of ischemic stroke more rapid and convenient, more accurately evaluate the state of brain injury in stroke patients and also guide stroke hypothermia treatment.


Assuntos
AVC Isquêmico , Elementos da Série dos Lantanídeos , Nanopartículas , Acidente Vascular Cerebral , Camundongos , Animais , Humanos , Elementos da Série dos Lantanídeos/uso terapêutico , Luminescência , Temperatura , Encéfalo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Diagnóstico Precoce
11.
Chemistry ; 18(26): 8004-7, 2012 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-22648988

RESUMO

Size control: Particles designed for imaging and therapy need to be size tunable to ensure their optimal performance. A highly reproducible procedure for the preparation of uniform, spherical, lanthanide-based nanoparticles (NPs) was developed. The size of the particles can be predefined to an accuracy of up to a few nanometers by microwave-generated temperature control and the choice of aging time (see figure).


Assuntos
Elementos da Série dos Lantanídeos , Micro-Ondas , Nanopartículas/química , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Modelos Químicos , Tamanho da Partícula
13.
J Mater Chem B ; 10(46): 9535-9564, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36385652

RESUMO

Metal-organic frameworks (MOFs) have attracted considerable attention as emerging nanomaterials. Based on their tunable size, high porosity, and large specific surface area, MOFs have a wide range of applications in the fields of chemistry, energy, and biomedicine. However, the MOF materials obtained from lanthanides with a unique electronic configuration as inorganic building units have unique properties such as optics, magnetism, and radioactivity. In this study, various synthetic methods for preparing MOF materials using lanthanides as inorganic building units are described. Combined with the characteristics of lanthanides, their application prospects of lanthanide-based MOFs in tumor diagnosis and treatment are emphasized. The authors hope to provide methodological reference for the construction of MOF materials of rare-earth elements, and to provide ideas and inspiration for their practical applications in the field of biomedicine.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Estruturas Metalorgânicas/uso terapêutico , Elementos da Série dos Lantanídeos/uso terapêutico , Eletrônica , Nanoestruturas/uso terapêutico , Porosidade , Neoplasias/diagnóstico , Neoplasias/terapia
14.
J Mater Chem B ; 10(23): 4501-4508, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35615958

RESUMO

Peroxynitrite anion (ONOO-), a product derived from reaction between reactive oxygen species (ROS) and nitric oxide (NO), is considered to be a more toxic reactive species than most ROS for cancer photodynamic therapy (PDT). To promote the PDT effect, a viable method is to develop rational strategies for efficient ONOO- generation at targeted tumor sites. Herein, a heterostructure nanocomposite containing ZnO-coated lanthanide nanoparticles (LnNPs) is reported for ONOO--based PDT. In this nanocomposite, Nd3+-doped LnNPs are employed to realize efficient NIR-light-triggered ROS generation by activating the triplet state of chlorin-e6 (Ce6) photosensitizers via a direct lanthanide-to-triplet sensitization mechanism. Meanwhile, ZnO in the composite catalyzes the decomposition of S-nitrosoglutathione (GSNO) to generate NO in the tumor microenvironment. The coupled system allows the combination of photo-induced ROS and NO to produce ONOO-, leading to drastically promoted cancer cell apoptosis and tumor growth inhibition. This study establishes a new apoptosis-inducing PDT agent, which is potentially active in drug resistant malignancies.


Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas Metálicas , Neoplasias , Fotoquimioterapia , Óxido de Zinco , Ânions/uso terapêutico , Humanos , Elementos da Série dos Lantanídeos/farmacologia , Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Ácido Peroxinitroso , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Microambiente Tumoral
15.
Bioconjug Chem ; 22(12): 2444-52, 2011 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-22053899

RESUMO

The therapeutic efficacies of radiolabeled biotin, pretargeted by monoclonal antibody (mAb)-streptavidin fusion protein CC49 scFvSA, were compared to those of radiolabeled mAb CC49, using the three radiolanthanides in an animal model of human colon cancer. The purpose of the present study was to compare antibody pretargeting to conventional radioimmunotherapy using (149)Pm, (166)Ho, or (177)Lu. Nude mice bearing LS174T colon tumors were injected sequentially with CC49 scFvSA, the blood clearing agent biotin-GalNAc(16), and (149)Pm-, (166)Ho-, or (177)Lu-DOTA-biotin. Tumor-bearing mice were alternatively administered (149)Pm-, (166)Ho-, or (177)Lu-MeO-DOTA-CC49. Therapy with pretargeted (149)Pm-,(166)Ho-, and (177)Lu-DOTA-biotin increased the median time of progression to a 1 g tumor to 50, 41, and 50 days post-treatment, respectively. Therapy with (149)Pm-,(166)Ho-, and (177)Lu-MeO-DOTA-CC49 increased the median time to progression to 53, 24, and 67 days post-treatment, respectively. In contrast, saline controls showed a median time to progression of 13 days postinjection. Treatment with pretargeted (149)Pm-, (166)Ho-, and (177)Lu-biotin or (149)Pm-, (166)Ho-, and (177)Lu-CC49 increased tumor doubling time to 18-36 days, compared to 3 days for saline controls. Among treated mice, 23% survived >84 days post-therapy, and 11% survived 6 months, but controls survived <29 days. Long-term survivors showed tumor growth inhibition or partial regression, extensive necrosis in residual masses, and no evidence of nontarget tissue toxicity at necropsy. Both pretargeted and conventional RIT demonstrated considerable efficacy in an extremely aggressive animal model of cancer. Our results identified (177)Lu as an optimal radiolanthanide for future evaluation of these agents in toxicity and multiple-dose therapy studies.


Assuntos
Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/radioterapia , Sistemas de Liberação de Medicamentos , Elementos da Série dos Lantanídeos/uso terapêutico , Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Estreptavidina/uso terapêutico , Animais , Biotina/análogos & derivados , Biotina/química , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Feminino , Humanos , Camundongos , Camundongos Nus , Compostos Organometálicos/química , Proteínas Recombinantes de Fusão/uso terapêutico
16.
Nanomedicine (Lond) ; 16(24): 2207-2242, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34533048

RESUMO

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.


Assuntos
Elementos da Série dos Lantanídeos , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Raios Infravermelhos , Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias/tratamento farmacológico
17.
Nanoscale ; 12(3): 1339-1348, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31859321

RESUMO

Lanthanides and actinides are used in a wide variety of applications, from energy production to life sciences. To address toxicity issues due to the chemical, and often radiological, properties of these elements, methods to quantify and recover them from industrial waste are necessary. When used in biomedicine, lanthanides and actinides are incorporated in compounds that show promising therapeutic and/or bioimaging properties, but lack robust strategies to target cancer and other pathologies. Furthermore, current decorporation protocols to respond to accidental actinide exposure rely on intravenous injections of soluble chelating agents, which are inefficient for treatment of inhaled radionuclides trapped in lungs. In recent years, nanoparticles have emerged as powerful tools in both industry and clinical settings. Because some inorganic nanoparticles are sensitive to external stimuli, such as light and magnetic fields, they can be used as building blocks for sensitive bioassays and separation techniques. In addition, nanoparticles can be functionalized with multiple ligands and act as carriers for selective delivery of therapeutic and contrast agents. This review summarizes and discusses recent progress on the use of nanoparticles in lanthanide and actinide chemistry. We examine different types of nanoparticles based on composition, functionalization, and properties, and we critically analyze their performance in a comparative mode. Our focus is two-pronged, including the nanoparticles free of lanthanides and actinides that are used for the detection, separation, or decorporation of f-block elements, as well as the nanoparticles that enhance the inherent properties of lanthanides and actinides for therapeutics, imaging and catalysis.


Assuntos
Elementos da Série Actinoide , Elementos da Série dos Lantanídeos , Nanopartículas Metálicas , Elementos da Série Actinoide/química , Elementos da Série Actinoide/uso terapêutico , Animais , Humanos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/uso terapêutico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico
18.
J Mater Chem B ; 8(45): 10257-10270, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33084729

RESUMO

The near-infrared II (NIR-II) light (1000-1700 nm) possesses deep penetration capability and high signal-to-noise ratios due to the advances of low autofluorescence and scattering in biological tissues. Differing from the traditional NIR-II-emitting nanoprobes such as carbon nanotubes (CNT), organic dyes, quantum dots (QDs), and polymer dots (PDs), lanthanide-doped NPs feature the characteristic of excellent photo-and-chemical stability, sharp emission peaks, longer lifetime, and larger anti-Stokes shift. These merits have impelled the development of NIR-II-emitting lanthanide NPs in biomedical applications at a terrific speed. In this mini-review, we discuss how to design efficient NIR-II-emitting lanthanide NPs and summarize their recent progress in bioimaging, therapy, and biosensing. Moreover, the limitations and future opportunities of NIR-II-emitting lanthanide NPs are also discussed.


Assuntos
Elementos da Série dos Lantanídeos/química , Substâncias Luminescentes/química , Nanopartículas/química , Imagem Óptica/métodos , Animais , Técnicas Biossensoriais/métodos , Humanos , Raios Infravermelhos , Elementos da Série dos Lantanídeos/uso terapêutico , Substâncias Luminescentes/uso terapêutico , Medições Luminescentes/métodos , Nanomedicina/métodos , Nanopartículas/uso terapêutico
19.
Biomaterials ; 230: 119670, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31837822

RESUMO

Two-dimensional (2D) ultrathin nanomaterials have shown extensive attention and potential biomedical applications in cancer theranostics. Herein, for the first time, we report the synthesis of monodisperse ultrathin lanthanum oxyiodide (LaOI) nanosheets with a thickness of merely 3 nm based on a facile wet chemistry strategy. By tuning the solvent composition and molar ratios of the precursors, we can modulate the shape and thickness of the nanosheets. Furthermore, a series of ultrathin lanthanide oxyiodides are synthesized by this method with tunable morphology. LaOI nanosheets as drug delivery platform showed ultrahigh anticancer doxorubicin (DOX) loading capacity (300 wt%) and pH-responsive release behaviour, as well as excellent cellular biocompatibility and efficiently intracellular nucleus delivery of DOX. LaOI with low dose DOX demonstrate enhanced cancer cell killing ability in vitro compared with DOX. The intravenous melanoma model shows that LaOI with low dose (1 mg mL-1) could significantly inhibit the tumor growth without side toxicity, relative to pure DOX. In addition, LaOI nanosheets also act as high resolution contrast agent for enhanced X-ray computed tomography imaging relative to the commercial iohexol. In summary, the LaOI nanosheets could serve as a competitive safe and low dose drug delivery platform for highly efficiently cancer imaging and therapy.


Assuntos
Antineoplásicos , Elementos da Série dos Lantanídeos , Neoplasias , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Elementos da Série dos Lantanídeos/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Medicina de Precisão , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
20.
ACS Appl Mater Interfaces ; 12(17): 19313-19323, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32275130

RESUMO

Though emerging as a promising therapeutic approach for cancers, the crucial challenge for photodynamic therapy (PDT) is activatable phototoxicity for selective cancer cell destruction with low "off-target" damage and simultaneous therapeutic effect prediction. Here, we design an upconversion nanoprobe for intracellular cathepsin B (CaB)-responsive PDT with in situ self-corrected therapeutic effect prediction. The upconversion nanoprobe is composed of multishelled upconversion nanoparticles (UCNPs) NaYF4:Gd@NaYF4:Er,Yb@NaYF4:Nd,Yb, which covalently modified with an antenna molecule 800CW for UCNPs luminance enhancement under NIR irradiation, photosensitizer Rose Bengal (RB) for PDT, Cy3 for therapeutic effect prediction, and CaB substrate peptide labeled with a QSY7 quencher. The energy of UCNPs emission at 540 nm is transferred to Cy3/RB and eventually quenched by QSY7 via two continuous luminance resonance energy transfer processes from interior UCNPs to its surface-extended QSY7. The intracellular CaB specifically cleaves peptide to release QSY7, which correspondingly activates RB with reactive oxygen species (ROS) generation for PDT and recovers Cy3 luminance for CaB imaging. UCNPs emission at 540 nm remains unchanged during the peptide cleavage process, which is served as an internal standard for Cy3 luminance correction, and the fluorescence intensity ratio of Cy3 over UCNPs (FI583/FI540) is measured for self-corrected therapeutic effect prediction. The proposed self-corrected upconversion nanoprobe implies significant potential in precise tumor therapy.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Carbocianinas/química , Catepsina B/química , Corantes Fluorescentes/química , Fluoretos/química , Fluoretos/efeitos da radiação , Fluoretos/uso terapêutico , Células HeLa , Humanos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/efeitos da radiação , Elementos da Série dos Lantanídeos/uso terapêutico , Luz , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos , Células NIH 3T3 , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Rosa Bengala/química , Ensaios Antitumorais Modelo de Xenoenxerto , Ítrio/química , Ítrio/efeitos da radiação , Ítrio/uso terapêutico
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