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1.
J Med Chem ; 67(14): 12428-12438, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38996002

RESUMO

Targeting Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages using RNAi nanotechnology represents an innovative and promising strategy in the diagnosis and treatment of atherosclerosis. Nevertheless, it remains elusive because of the current challenges associated with the systemic delivery of siRNA nanoparticle (NP) to atheromatous plaques and the complexity of atherosclerotic plaques. Here, we demonstrate the potential of a thienothiadiazole-based near-infrared-II (NIR-II) organic aggregation-induced emission (AIE) platform encapsulated with the Camk2g siRNA to effectively target CaMKIIγ in macrophages for dynamic imaging and image-guided gene therapy of atherosclerosis. The nanoparticles effectively decreased CaMKIIγ expression and increased the expression of the efferocytosis receptor MerTK in plaque macrophages, leading to a reduction in the necrotic core area of the lesion in an aortic plaque model. Our theranostic approach highlights the substantial promise of near-infrared II (NIR-II) AIEgens for imaging and image-guided therapy of atherosclerosis.


Assuntos
Aterosclerose , Imagem Óptica , RNA Interferente Pequeno , Animais , Humanos , Camundongos , Aterosclerose/diagnóstico por imagem , Aterosclerose/terapia , Raios Infravermelhos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Nanopartículas/química , Placa Aterosclerótica/diagnóstico por imagem , RNA Interferente Pequeno/química , RNA Interferente Pequeno/uso terapêutico , Tiadiazóis/química , Tiadiazóis/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/química , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo
2.
Front Pharmacol ; 15: 1352373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567350

RESUMO

Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer.

3.
J Med Chem ; 67(3): 1861-1871, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38247270

RESUMO

Fluorescence and photoacoustic (PA) imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has garnered massive interest owing to high maximum permissible exposure of light, reduced autofluorescence, and improved deep penetration. However, active targeted NIR-II photoacoustic/NIR-IIa fluorescence imaging of glioma under NIR-II excitation has been seldom reported, which is partly ascribable to the lack of suitable materials. In this study, a small-molecule-based αvß3-targeted NIR-II photoacoustic/NIR-IIa fluorescent probe IR-32p was generated and subsequently evaluated in U87MG tumor-bearing mice excited with NIR-I and NIR-II light. Exceptional dual-modal imaging properties such as good tumor uptake, high targeting specificity, and high tumor contrast were achieved in an orthotopic glioma model under 1020/1064 nm excitation, exhibiting a superior imaging depth of glioma through the skull. Our study introduces an outstanding dual-modal contrast agent with NIR-II absorption and confirms the superiority of NIR-II excitation over NIR-I in in vivo NIR-II/PA imaging.


Assuntos
Glioma , Técnicas Fotoacústicas , Camundongos , Animais , Corantes Fluorescentes , Técnicas Fotoacústicas/métodos , Glioma/diagnóstico por imagem , Imagem Óptica , Análise Espectral
4.
Adv Sci (Weinh) ; 10(36): e2303597, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37915127

RESUMO

Ribonucleic acid (RNA) drugs have shown promising therapeutic effects for various diseases in clinical and preclinical studies, owing to their capability to regulate the expression of genes of interest or control protein synthesis. Different strategies, such as chemical modification, ligand conjugation, and nanotechnology, have contributed to the successful clinical translation of RNA medicine, including small interfering RNA (siRNA) for gene silencing and messenger RNA (mRNA) for vaccine development. Among these, nanotechnology can protect RNAs from enzymatic degradation, increase cellular uptake and cytosolic transportation, prolong systemic circulation, and improve tissue/cell targeting. Here, a focused overview of stimuli-responsive nanotechnologies for RNA delivery, which have shown unique benefits in promoting RNA bioactivity and cell/organ selectivity, is provided. Many tissue/cell-specific microenvironmental features, such as pH, enzyme, hypoxia, and redox, are utilized in designing internal stimuli-responsive RNA nanoparticles (NPs). In addition, external stimuli, such as light, magnetic field, and ultrasound, have also been used for controlling RNA release and transportation. This review summarizes a wide range of stimuli-responsive NP systems for RNA delivery, which may facilitate the development of next-generation RNA medicines.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Nanotecnologia , Preparações Farmacêuticas , RNA Interferente Pequeno , RNA Mensageiro
5.
Mikrochim Acta ; 190(12): 462, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945912

RESUMO

Fluorescent lateral flow immunoassay (LFA), one tool in point of care testing (POCT) systems for breast cancer, has attracted attention because it is quick, simple, and convenient. However, samples and the constituent material exhibit autofluorescence in the visible region, which is a very large obstacle in the development of fluorescent LFAs. The autofluorescence of biological samples is scarcely found in the second near-infrared (NIR-II) range and samples scatter and absorb less NIR-II light than visible light. Here, we report an NIR-II QD-LFA platform using the NIR-II fluorescent Ag2Se quantum dots (QDs) with 1020 nm emission encapsulated into polystyrene beads as fluorescent probes. The NIR-II LFA platform was established to detect breast cancer tumour markers (CEA and CA153) within 15 min with a low limit of detection (CEA: 0.768 ng mL-1, CA153: 1.192 U mL-1), high recoveries (93.7% ~ 108.8%), and relative standard deviations (RSDs) of less than 10%. This study demonstrated the potential of NIR-II Ag2Se polystyrene beads as a fluorescent probe in LFA for rapid and accurate identification of biomarkers. They are suited for use in professional situations.


Assuntos
Neoplasias , Poliestirenos , Biomarcadores Tumorais , Corantes Fluorescentes , Imunoensaio , Luz
6.
Acta Pharm Sin B ; 13(11): 4578-4590, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37969732

RESUMO

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

7.
ACS Nano ; 17(15): 14347-14405, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37486125

RESUMO

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.


Assuntos
Corantes Fluorescentes , Substâncias Luminescentes , Corantes Fluorescentes/química , Luminescência , Diagnóstico por Imagem , Atenção à Saúde
8.
Analyst ; 148(15): 3543-3550, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37387232

RESUMO

Dopamine (DA) is an important small-molecule neurotransmitter, which is closely related to the development of many neurological diseases and has received increasing attention in the diagnosis of neurological diseases. Currently, the assays of the detection of dopamine such as electrochemical and colorimetric methods have low sensitivity, poor selectivity and susceptibility to interference, which limit the accurate quantification of dopamine. Fluorescence anisotropy immunoassay is a traditional analytical method in which the quantification is based on the change in fluorescence anisotropy values observed when fluorescence molecules are bound to a certain volume and mass of the material. Since dopamine is a small molecule with small volume and mass, we took advantage of the good photostability of the second near-infrared window (NIR-II) quantum dots (QDs) and the low spontaneous interference of the substrate, and designed a biosensor dopamine fluorescence anisotropy probe streptavidin biosensor (DFAP-SAB) based on the NIR-II QDs combined with streptavidin signal amplification to achieve rapid and separation-free detection of dopamine in human serum. The detection signal has a good linearity between 50 nM and 3000 nM with a detection limit of 11.2 nM. The application of NIR-II QDs provides the possibility of biosensor applications for complex samples. The construction of the streptavidin signal amplification device provides a new idea for small molecule detection.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Humanos , Pontos Quânticos/química , Dopamina , Estreptavidina , Técnicas Biossensoriais/métodos , Imunoensaio , Limite de Detecção
9.
Gastroenterology ; 165(3): 746-761.e16, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37263311

RESUMO

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.


Assuntos
Endostatinas , Proteômica , Camundongos , Animais , Humanos , Endostatinas/metabolismo , Endostatinas/farmacologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Fibrose , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Matriz Extracelular , Macrófagos/metabolismo
10.
J Vis Exp ; (193)2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-37010297

RESUMO

As an emerging imaging technology, near-infrared II (NIR-II, 1000-1700 nm) fluorescence imaging has significant potential in the biomedical field, owing to its high sensitivity, deep tissue penetration, and superior imaging with spatial and temporal resolution. However, the method to facilitate the implementation of NIR-II fluorescence imaging for some urgently needed fields, such as medical science and pharmacy, has puzzled relevant researchers. This protocol describes in detail the construction and bioimaging applications of a NIR-II fluorescence molecular probe, HLY1, with a D-A-D (donor-acceptor-donor) skeleton. HLY1 showed good optical properties and biocompatibility. Furthermore, NIR-II vascular and tumor imaging in mice was performed using a NIR-II optics imaging device. Real-time high-resolution NIR-II fluorescence images were acquired to guide the detection of tumors and vascular diseases. From probe preparation to data acquisition, the imaging quality is greatly improved, and the authenticity of the NIR-II molecular probes for data recording in intravital imaging is ensured.


Assuntos
Corantes Fluorescentes , Neoplasias , Animais , Camundongos , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Microscopia Intravital
11.
Nano Lett ; 23(9): 3661-3668, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37093620

RESUMO

Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment. We developed ROS-responsive oligomer-based polymeric NPs and applied them to test a combination of p53 mRNA and indocyanine green (ICG). The ROS-triggered disassembly of the NPs could promote mRNA translation efficiency, whereby p53 expression induced apoptosis of lung tumor cells. Meanwhile, the released ICG could lead to generation of ROS under 808 nm laser irradiation to induce photodynamic therapy. The NP codelivery of p53 mRNA and ICG demonstrated an effective and safe anti-tumor effect in a lung cancer model.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Verde de Indocianina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Polímeros/metabolismo , Linhagem Celular Tumoral
12.
J Funct Biomater ; 14(3)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36976074

RESUMO

Atopic dermatitis (AD) is the most common heterogeneous skin disease. Currently, effective primary prevention approaches that hamper the occurrence of mild to moderate AD have not been reported. In this work, the quaternized ß-chitin dextran (QCOD) hydrogel was adopted as a topical carrier system for topical and transdermal delivery of salidroside for the first time. The cumulative release value of salidroside reached ~82% after 72 h at pH 7.4, while in vitro drug release experiments proved that QCOD@Sal (QCOD@Salidroside) has a good, sustained release effect, and the effect of QCOD@Sal on atopic dermatitis mice was further investigated. QCOD@Sal could promote skin repair or AD by modulating inflammatory factors TNF-α and IL-6 without skin irritation. The present study also evaluated NIR-II image-guided therapy (NIR-II, 1000-1700 nm) of AD using QCOD@Sal. The treatment process of AD was monitored in real-time, and the extent of skin lesions and immune factors were correlated with the NIR-II fluorescence signals. These attractive results provide a new perspective for designing NIR-II probes for NIR-II imaging and image-guided therapy with QCOD@Sal.

13.
Molecules ; 28(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36677834

RESUMO

Transient receptor potential vanillin 3 (TRPV3) is a member of the transient receptor potential (TRP) superfamily. As a Ca2+-permeable nonselective cation channel, TRPV3 can recognize thermal stimulation (31-39 °C), and it plays an important regulatory role in temperature perception, pain transduction, skin physiology, inflammation, cancer and other diseases. TRPV3 is not only activated by the changes in the temperature, but it also can be activated by a variety of chemical and physical stimuli. Selective TRPV3 agonists and antagonists with regulatory effects and the physiological functions for clinical application are highly demanded. In recent years, significant progress has been made in the study of TRPV3, but there is still a lack of modulators with a strong affinity and excellent selectivity. This paper reviews the functional characteristics of TRPV3 in terms of the structure, diseases and the research on TRPV3 modulators.


Assuntos
Canais de Cátion TRPV , Humanos , Inflamação , Dor , Temperatura , Canais de Cátion TRPV/química
14.
Angew Chem Int Ed Engl ; 62(13): e202214875, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36545827

RESUMO

Despite significant effort, a majority of heavy-atom-free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near-infrared (NIR) heavy-atom-free photosensitizers. Based on a series of thiopyrylium-based NIR-II (1000-1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron-rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)-domain, contributing to a ≈6-fold reduction in energy gap (ΔEST ), a ≈10-fold accelerated ISC process, and a ≈31.49-fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD-PEG2K lung-targeting dots enabled real-time NIR-II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.


Assuntos
Infecções por Coronavirus , Coronavirus , Humanos , Fármacos Fotossensibilizantes/farmacologia , Tiofenos
15.
Chem Sci ; 13(27): 8193-8202, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35919436

RESUMO

The origin of the enormous catalytic power of enzymes has been extensively studied through experimental and computational approaches. Although precise mechanisms are still subject to much debate, enzymes are thought to catalyze reactions by stabilizing transition states (TSs) or destabilizing ground states (GSs). By exploring the catalysis of various types of enzyme-substrate noncovalent interactions, we found that catalysis by TS stabilization and the catalysis by GS destabilization share common features by reducing the free energy barriers (ΔG ‡s) of reactions, but are different in attaining the requirement for ΔG ‡ reduction. Irrespective of whether enzymes catalyze reactions by TS stabilization or GS destabilization, they reduce ΔG ‡s by enhancing the charge densities of catalytic atoms that experience a reduction in charge density between GSs and TSs. Notably, in TS stabilization, the charge density of catalytic atoms is enhanced prior to enzyme-substrate binding; whereas in GS destabilization, the charge density of catalytic atoms is enhanced during the enzyme-substrate binding. Results show that TS stabilization and GS destabilization are not contradictory to each other and are consistent in reducing the ΔG ‡s of reactions. The full mechanism of enzyme catalysis includes the mechanism of reducing ΔG ‡ and the mechanism of enhancing atomic charge densities. Our findings may help resolve the debate between TS stabilization and GS destabilization and assist our understanding of catalysis and the design of artificial enzymes.

16.
Chem Commun (Camb) ; 58(45): 6546-6549, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579558

RESUMO

Novel NIR-II Ru(II) polypyridyl fluorophore Ru-1 dots for synergistic chemo-photothermal therapy against 4T1 tumors were designed and synthesized. Guided by in vivo NIR-II fluorescence imaging, the synergistic therapeutic efficacy, intracellular delivery, and biodistribution of the Ru-1 dots were precisely tracked in real-time.


Assuntos
Nanopartículas , Rutênio , Linhagem Celular Tumoral , Corantes Fluorescentes , Fototerapia/métodos , Terapia Fototérmica , Distribuição Tecidual
17.
J Control Release ; 342: 157-169, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34998914

RESUMO

Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1-4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications.


Assuntos
Nanopartículas , Nanomedicina Teranóstica , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , Nanomedicina Teranóstica/métodos
18.
J Med Chem ; 65(3): 2225-2237, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-34994554

RESUMO

The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.


Assuntos
Complexos de Coordenação/química , Raios Infravermelhos , Rutênio/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/uso terapêutico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Hipertermia Induzida , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fenazinas/química , Terapia Fototérmica/métodos , Polietilenoglicóis/química , Teoria Quântica , Espectroscopia de Luz Próxima ao Infravermelho
19.
J Med Chem ; 65(3): 2078-2090, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-34949094

RESUMO

Complete excision of the last remaining 1-2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000-1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48-144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/química , Corantes Fluorescentes/química , Glioma/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Desenho de Fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacocinética , Glioma/terapia , Meia-Vida , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Teoria Quântica , Cirurgia Assistida por Computador , Distribuição Tecidual , Transplante Heterólogo
20.
Chem Rev ; 122(1): 209-268, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-34664951

RESUMO

In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.


Assuntos
Nanotubos de Carbono , Medicina de Precisão , Corantes Fluorescentes , Humanos , Imagem Molecular , Imagem Óptica/métodos
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