Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.032
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36175373

RESUMO

Designing luminescence lifetime sensor in the second near-infrared (NIR-II) window is a great challenge due to the difficult structural construction. Here, we report a tumor redox responsive and easy synthesized material, amorphous manganese oxide (MnO x ) with indirect bandgap of 1.02 eV as energy acceptor to build a luminescence resonance energy transfer (LRET) toolbox for universally regulating NIR-I to NIR-II luminescence lifetimes of lanthanide nanoparticles, in which energy transfer is based on matched energy gap instead of conventional overlapped spectra. We further utilize Yb 3+ doped YbNP@MnO x as NIR-II luminescence lifetime sensor to realize in vitro quantitative redox visualization with relative errors under 5% after mouse skin coverage. Furthermore, HepG2 cells and tumors with high redox state have been accurately distinguished by NIR-II luminescence lifetime imaging. The quantified intracellular and intratumoral glutathione (GSH) levels are highly consistent with the commercial kit results, illustrating the reliable redox visualization ability under bio-tissue.

3.
Nat Commun ; 13(1): 5091, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042210

RESUMO

X-ray-induced photodynamic therapy utilizes penetrating X-rays to activate reactive oxygen species in deep tissues for cancer treatment, which combines the advantages of photodynamic therapy and radiotherapy. Conventional therapy usually requires heavy-metal-containing inorganic scintillators and organic photosensitizers to generate singlet oxygen. Here, we report a more convenient strategy for X-ray-induced photodynamic therapy based on a class of organic phosphorescence nanoscintillators, that act in a dual capacity as scintillators and photosensitizers. The resulting low dose of 0.4 Gy and negligible adverse effects demonstrate the great potential for the treatment of deep tumours. These findings provide an optional route that leverages the optical properties of purely organic scintillators for deep-tissue photodynamic therapy. Furthermore, these organic nanoscintillators offer an opportunity to expand applications in the fields of biomaterials and nanobiotechnology.


Assuntos
Fotoquimioterapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Radiografia , Oxigênio Singlete , Raios X
4.
Exp Hematol Oncol ; 11(1): 46, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974381

RESUMO

BACKGROUND: Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population. METHODS: Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls. RESULTS: The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506-0.729] for one dose, 0.745 [0.712-0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094-0.386]; two doses: 0.277 [0.190-0.386]) than HSCT counterparts (one dose: 0.779 [0.666-0.862]; two doses: 0.793 [0.762-0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population. CONCLUSIONS: This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.

5.
EJNMMI Res ; 12(1): 52, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984529

RESUMO

BACKGROUND: This pilot study was designed to evaluate the diagnostic value of 68 Ga-PSMA-617 and 18F-FDG PET/CT in adenoid cystic carcinoma (ACC) and to assess the safety and therapeutic response to PSMA radioligand therapy (RLT) in ACC patients. METHODS: Thirty patients pathologically diagnosed with ACC were recruited into the cohort. Each patient underwent 68 Ga-PSMA-617 and 18F-FDG PET/CT within 1 week. The number and SUVmax of PET-positive lesions were recorded and compared. Four patients accepted RLT using 177Lu-EB-PSMA-617, in a dosage of approximately 1.85 GBq (50 mCi) per cycle for up to 3 cycles. RESULTS: Compared with 18F-FDG, 68 Ga-PSMA-617 revealed more PET-positive extrapulmonary tumors (157 vs. 141, P = 0.016) and higher SUVmax (8.8 ± 3.6 vs. 6.4 ± 4.2, P = 0.027). However, 68 Ga-PSMA-617 revealed less PET-positive pulmonary lesions (202 vs. 301, P < 0.001) and lower SUVmax of tumors (3.1 ± 3.0 vs. 4.2 ± 3.9, P < 0.001) than 18F-FDG. The combination of 68 Ga-PSMA-617 and 18F-FDG can detect 469 PET-positive lesions, which was superior to each alone (469 vs. 359 vs. 442, P < 0.001). Two patients achieved remarkable response after PSMA RLT, while the other two patients showed reduced tumor uptake of recurrent foci, lung and liver metastases, whereas increased SUVmax of bone metastases. CONCLUSIONS: 68 Ga-PSMA-617 PET/CT is a valuable imaging modality for the detection of ACC and combining with 18F-FDG PET/CT will achieve a higher detection efficiency. PSMA RLT may be a promising treatment for ACC and is worth of further investigation. TRIAL REGISTRATION: Diagnosis of Adenoid Cystic Carcinoma on 68 Ga-PSMA-617 PET-CT and Therapy With 177Lu-EB-PSMA-617 (NCT04801264, Registered 16 March 2021, retrospectively registered). URL of registry: https://clinicaltrials.gov/ct2/show/NCT04801264 .

6.
Mol Pharm ; 19(9): 3405-3411, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35972444

RESUMO

Noninvasive PET molecular imaging using radiopharmaceuticals is important to classify breast cancer in the clinic. The aim of this study was to investigate the combination of 18F-FDG and 18F-Alfatide II for predicting molecular subtypes of invasive breast cancer. Forty-four female patients with clinically suspected breast cancer were recruited and underwent 18F-FDG and 18F-Alfatide II PET/CT within a week. Tracer uptake in breast lesions was assessed using the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and SUVmax ratio of 18F-FDG to 18F-Alfatide II (FAR). Invasive breast cancer lesions were further classified as luminal A subtype, luminal B subtype, human epidermal growth factor receptor-2 (HER2) overexpressing subtype, and triple negative subtype according to the expression of the estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67. Among 44 patients, 35 patients were pathologically diagnosed with invasive breast cancer. The SUVmax and SUVmean of 18F-FDG were significantly higher in the ER-negative group than those in the ER-positive group, as well as in the PR-negative group than those in the PR-positive group. However, the SUVmax and SUVmean of 18F-Alfatide II were higher in the ER-positive group and the PR-positive group. By combining 18F-FDG and 18F-Alfatide II, the FAR was lower in the ER-positive group and the PR-positive group. The HER2 overexpressing subtype showed the highest SUVmax and SUVmean for 18F-FDG while the luminal B (HER2 negative) subtype revealed the lowest values. The luminal B (HER2 negative) subtype showed the highest 18F-Alfatide II SUVmax, while the triple negative subtype showed the lowest 18F-Alfatide II SUVmax. The FAR was the lowest in the luminal B (HER2 negative) subtype and much higher in the HER2 overexpressing and triple negative subtypes. FAR less than 1 predicted the luminal B (HER2 negative) subtype with high specificity (93.1%) and NPV (90%). FAR greater than 3 predicted the HER2 overexpressing subtype and triple negative subtype (namely, the nonluminal subtype) with very high specificity (100%) and PPV (100%). In summary, FAR, the combined PET parameter of 18F-FDG and 18F-Alfatide II, can be used to predict molecular subtypes of invasive breast cancer, especially for the luminal B (HER2 negative) subtype and the nonluminal subtype.


Assuntos
Neoplasias da Mama , Fluordesoxiglucose F18 , Neoplasias da Mama/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Peptídeos Cíclicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Receptor ErbB-2/metabolismo , Estudos Retrospectivos
8.
Theranostics ; 12(10): 4536-4547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832086

RESUMO

Near-infrared-II (NIR-II) dyes could be encapsulated by either exogenous or endogenous albumin to form stable complexes for deep tissue bioimaging. However, we still lack a complete understanding of the interaction mechanism of the dye@albumin complex. Studying this principle is essential to guide efficient dye synthesis and develop NIR-II probes with improved brightness, photostability, etc. Methods: Here, we screen and test the optical and chemical properties of dye@albumin fluorophores, and systematically investigate the binding sites and the relationship between dye structures and binding degree. Super-stable cyanine dye@albumin fluorophores are rationally obtained, and we also evaluate their pharmacokinetics and long-lasting NIR-II imaging abilities. Results: We identify several key parameters of cyanine dyes governing the supramolecular/covalent binding to albumin, including a six-membered ring with chlorine (Cl), the small size of side groups, and relatively high hydrophobicity. The tailored fluorophore (IR-780@albumin) exhibits much-improved photostability, serving as a long-lasting imaging probe for NIR-II bioimaging. Conclusion: Our study reveals that the chloride-containing cyanine dyes with the above-screened chemical structure (e.g. IR-780) could be lodged into albumin more efficiently, producing a much more stable fluorescent probe. Our finding partly solves the photobleaching issue of clinically-available cyanine dyes, enriching the probe library for NIR-II bioimaging and imaging-guided surgery.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Albuminas , Corantes Fluorescentes/química , Imagem Óptica/métodos
9.
Anal Chem ; 94(29): 10479-10486, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35834188

RESUMO

As the key player of a new restriction modification system, DNA phosphorothioate (PT) modification, which swaps oxygen for sulfur on the DNA backbone, protects the bacterial host from foreign DNA invasion. The identification of PT sites helps us understand its physiological defense mechanisms, but accurately quantifying this dynamic modification remains a challenge. Herein, we report a simple quantitative analysis method for optical mapping of PT sites in the single bacterial genome. DNA molecules are fully stretched and immobilized in a microfluidic chip by capillary flow and electrostatic interactions, improving the labeling efficiency by maximizing exposure of PT sites on DNA while avoiding DNA loss and damage. After screening 116 candidates, we identified a bifunctional chemical compound, iodoacetyl-polyethylene glycol-biotin, that can noninvasively and selectively biotinylate PT sites, enabling further labeling with streptavidin fluorescent nanoprobes. With this method, PT sites in PT+ DNA can be easily detected by fluorescence, while almost no detectable ones were found in PT- DNA, achieving real-time visualization of PT sites on a single DNA molecule. Collectively, this facile genome-wide PT site detection method directly characterizes the distribution and frequency of DNA modification, facilitating a better understanding of its modification mechanism that can be potentially extended to label DNAs in different species.


Assuntos
Genoma Bacteriano , Microfluídica , DNA , DNA Bacteriano/genética , Enxofre
10.
Adv Drug Deliv Rev ; 188: 114456, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35843505

RESUMO

With the increasing understanding of various biological functions mediated by reactive oxygen species (ROS) in the immune system, a number of studies have been designed to develop ROS-generating/eliminating strategies to selectively modulate immunogenicity for disease treatment. These strategies potentially exploit ROS-modulating inorganic biomaterials to harness host immunity to maximize the therapeutic potency by eliciting a favorable immune response. Inorganic biomaterial-guided in vivo ROS scavenging can exhibit several effects to: i) reduce the secretion of pro-inflammatory factors, ii) induce the phenotypic transition of macrophages from inflammatory M1 to immunosuppressive M2 phase, iii) minimize the recruitment and infiltration of immune cells. and/or iv) suppress the activation of nuclear factor kappa-B (NF-κB) pathway. Inversely, ROS-generating inorganic biomaterials have been found to be capable of: i) inducing immunogenic cell death (ICD), ii) reprograming tumor-associated macrophages from M2 to M1 phenotypes, iii) activating inflammasomes to stimulate tumor immunogenicity, and/or iv) recruiting phagocytes for antimicrobial therapy. This review provides a systematic and up-to-date overview on the progress related to ROS-nanotechnology mediated immunomodulation. We highlight how the ROS-generating/eliminating inorganic biomaterials can converge with immunomodulation and ultimately elicit an effective immune response against inflammation, autoimmune diseases, and/or cancers. We expect that contents presented in this review will be beneficial for the future advancements of ROS-based nanotechnology and its potential applications in this evolving field.


Assuntos
Materiais Biocompatíveis , NF-kappa B , Imunidade , Macrófagos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
J Colloid Interface Sci ; 625: 831-838, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35777093

RESUMO

Chirality has been proved to play a significant role in tuning cell behaviors and controlling cellular functions. Up to now, almost all the chirality origins of extracellular microenvironment are belong to chiral ligands induction or direct chiral patterns. In this study, chiral gold nanoclusters (L/D-AuNC) loaded on two-dimensional gold nanoparticle films (L/D-film) with multiple chirality origins were prepared to regulate the adhesion and differentiation of mouse bone marrow mesenchymal stem cells (MSCs). MSCs on the D-film exhibited higher cell density and larger spreading area, and more cells differentiated into osteoblasts. Compared with D-film, L-film has a lower cell density and smaller spreading area, and more adipoblasts are achieved. The corresponding expression results of osteogenic differentiation marker (RUNX2) also confirmed the above experimental phenomenon. These results demonstrated that the chirality of clusters has great effect on the direction of cell fate.


Assuntos
Nanopartículas Metálicas , Osteogênese , Animais , Diferenciação Celular , Ouro , Camundongos , Células-Tronco
12.
Chem Soc Rev ; 51(18): 7692-7714, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35861173

RESUMO

Biomedical fluorescence imaging in the second near-infrared (NIR-II, 100-1700 nm) window provides great potential for visualizing physiological and pathological processes, owing to the reduced tissue absorption, scattering, and autofluorescence. Various types of NIR-II probes have been reported in the past decade. Among them, NIR-II organic/inorganic nanohybrids have attracted widespread attention due to their unique properties by integrating the advantages of both organic and inorganic species. Versatile organic/inorganic nanohybrids provide the possibility of realizing a combination of functions, controllable size, and multiple optical features. This tutorial review summarizes the reported organic and inorganic species in nanohybrids, and their biomedical applications in NIR-II fluorescence and lifetime imaging. Finally, the challenges and outlook of organic/inorganic nanohybrids in biomedical applications are discussed.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Imagem Óptica/métodos
13.
J Med Chem ; 65(12): 8245-8257, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35658448

RESUMO

The fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), has become a valuable target for tumor diagnosis and therapy. However, most FAP-based radioligands show insufficient tumor uptake and retention. In this study, three novel albumin-binding FAP ligands (denoted as FSDD0I, FSDD1I, and FSDD3I) were labeled with 68Ga and 177Lu to overcome these limitations. Cell-based studies and molecular docking assays were performed to identify the specificity and protein-binding properties for FAP. Positron emission tomography (PET) scans in human hepatocellular carcinoma patient-derived xenografts (HCC-PDXs) animal models revealed longer blood retention of 68Ga-FSDD0I than 68Ga-FAPI-04, 68Ga-FSDD1I, and 68Ga-FSDD3I. Remarkably, 68Ga-FSDD3I had prominent tumor-to-nontarget (T/NT) ratios. The prominent tumor retention properties of 177Lu-FSDD0I in single photon emission computed tomography (SPECT) imaging and biodistribution studies were demonstrated. In summary, this study reports a proof-of-concept study of albumin-binding radioligands for FAP-targeted imaging and targeted radionuclide therapy (TRT).


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Albuminas/metabolismo , Animais , Fibroblastos/metabolismo , Radioisótopos de Gálio , Humanos , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Medicina de Precisão , Distribuição Tecidual
14.
Adv Mater ; 34(31): e2203734, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35681250

RESUMO

Alloying is an efficient chemistry to tailor the properties of metal clusters. As a class of promising radiosensitizers, most previously reported metal clusters exhibit unitary function and cannot overcome radioresistance of hypoxic tumors. Here, atomically precise alloy clusters Pt2 M4 (M = Au, Ag, Cu) are synthesized with bright luminescence and adequate biocompatibility, and their composition-dependent enzyme mimicking activity and radiosensitizing effect is explored. Specifically, only the Pt2 Au4 cluster displays catalase-like activity, while the others do not have clusterzyme properties, and its radiosensitizing effect is the highest among all the alloy clusters tested. By taking advantage of the sustainable production of O2 via the decomposition of endogenous H2 O2 , the Pt2 Au4 cluster modulates tumor hypoxia as well as increases the efficacy of radiotherapy. This work thus advances the cluster alloying strategy to produce multifunctional therapeutic agents for improving hypoxic tumor therapy.


Assuntos
Neoplasias , Radiossensibilizantes , Ligas , Humanos , Hipóxia , Neoplasias/radioterapia , Radiossensibilizantes/farmacologia , Hipóxia Tumoral
15.
J Mater Chem B ; 10(26): 5028-5034, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35723599

RESUMO

Gold nanoclusters exhibit significant potential in antimicrobial applications due to their good stability and desirable biocompatibility in the mammalian cell model. However, most of the previously reported gold nanocluster antimicrobial agents do not have an atomic-precise structure, causing difficulties in understanding the structure-property correlation. In this study, structurally defined gold-levonorgestrel clusters, named Au8(C21H27O2)8 (Au8NCs) and Au10(C21H27O2)10 (Au10NCs), with the same ligand-to-metal ratio but different inner cores were prepared for antibacterial activity investigations, demonstrating that Au8NCs exhibited a stronger antibacterial activity owing to the more significant damage it causes on the bacteria wall and membrane, and a stronger inhibition of glutathione reductase activity in bacteria. The leakage of the intracellular components and enzyme inhibition caused an imbalance of the intracellular antioxidant defence system, and consequently killed bacteria. These results indicated that the structure of gold nanoclusters has an important effect on their biological activity, indicating that it as a key factor to consider in the future design of antimicrobial agents.


Assuntos
Anti-Infecciosos , Ouro , Levanogestrel , Nanopartículas Metálicas , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Glutationa Redutase/antagonistas & inibidores , Ouro/química , Ouro/farmacologia , Levanogestrel/química , Levanogestrel/farmacologia , Nanopartículas Metálicas/química
16.
Nat Immunol ; 23(7): 1109-1120, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761081

RESUMO

Nonimmune cells can have immunomodulatory roles that contribute to healthy development. However, the molecular and cellular mechanisms underlying the immunomodulatory functions of erythroid cells during human ontogenesis remain elusive. Here, integrated, single-cell transcriptomic studies of erythroid cells from the human yolk sac, fetal liver, preterm umbilical cord blood (UCB), term UCB and adult bone marrow (BM) identified classical and immune subsets of erythroid precursors with divergent differentiation trajectories. Immune-erythroid cells were present from the yolk sac to the adult BM throughout human ontogenesis but failed to be generated in vitro from human embryonic stem cells. Compared with classical-erythroid precursors, these immune-erythroid cells possessed dual erythroid and immune regulatory networks, showed immunomodulatory functions and interacted more frequently with various innate and adaptive immune cells. Our findings provide important insights into the nature of immune-erythroid cells and their roles during development and diseases.


Assuntos
Células Precursoras Eritroides , Transcriptoma , Adulto , Diferenciação Celular/genética , Células Eritroides , Sangue Fetal , Humanos , Recém-Nascido , Saco Vitelino
17.
Angew Chem Int Ed Engl ; 61(38): e202206763, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-35762745

RESUMO

Supramolecular polymers (SPs) have attracted broad interest because of their intriguing features and functions. Host-guest interactions often impart tunable physicochemical properties, reversible hierarchical organization, and stimuli-responsiveness to SPs for diverse biomedical applications. Characterized by strong but dynamic interactions with guest molecules, cucurbit[n]uril (CB[n]) has shown great potential as an important building block of various functional polymers for biomedical applications. In this Minireview, we summarize the most recent examples regarding the design, fabrication, and biomedical applications of CB[n]-based supramolecular polymers (CSPs), which are categorized as noncovalent and covalent CSPs according to the interactions between the CB[n] and polymer backbones. The design principles of CSPs and their unique advantages for biomedical applications, as well as the developmental trends and future perspectives of this cross-disciplinary area are also discussed.


Assuntos
Compostos Macrocíclicos , Polímeros , Compostos Heterocíclicos com 2 Anéis , Imidazolidinas , Polímeros/química
18.
Mol Pharm ; 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35652897

RESUMO

Immune checkpoint blockers (ICBs) targeting programmed death receptor 1 (PD-1) ligand 1 (PD-L1) for immunotherapy have radically reformed oncology. It is of great significance to enhance the response rate of ICB in cancer patients. Here, a radioiodinated anti-PD-L1 antibody (131I-αPD-L1) was developed for PD-L1-targeted single-photon emission computed tomography (SPECT) imaging and αPD-L1 immunotherapy. Flow cytometry and immunofluorescence staining were performed to identify PD-L1 upregulation in a time- and dose-dependent manner after being induced by 131I-αPD-L1. ImmunoSPECT imaging and biodistributions of 131I-αPD-L1 in CT26, MC38, 4T1, and B16F10 tumor models were conducted to visualize the high tumor uptake and low background signal. Compared to monotherapy alone, concurrent administration of αPD-L1 mAb and 131I-αPD-L1 revealed improved tumor control in murine tumor models. The combination of 11.1 MBq of 131I-αPD-L1 and 200 µg of αPD-L1 mAb resulted in significant tumor growth delay and prolonged survival. This radioligand synergized immunotherapy strategy holds great potential for cancer management.

19.
Nat Commun ; 13(1): 2513, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523769

RESUMO

Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.


Assuntos
Óxido Nítrico , Traumatismo por Reperfusão , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Fígado/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Platina/farmacologia , Platina/uso terapêutico , Espécies Reativas de Oxigênio/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
20.
Nat Commun ; 13(1): 2853, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606352

RESUMO

The second near-infrared (NIR-II) window is a fundamental modality for deep-tissue in vivo imaging. However, it is challenging to synthesize NIR-II probes with high quantum yields (QYs), good biocompatibility, satisfactory pharmacokinetics, and tunable biological properties. Conventional long-wavelength probes, such as inorganic probes (which often contain heavy metal atoms in their scaffolds) and organic dyes (which contain large π-conjugated groups), exhibit poor biosafety, low QYs, and/or uncontrollable pharmacokinetic properties. Herein, we present a bioengineering strategy that can replace the conventional chemical synthesis methods for generating NIR-II contrast agents. We use a genetic engineering technique to obtain a series of albumin fragments and recombinant proteins containing one or multiple domains that form covalent bonds with chloro-containing cyanine dyes. These albumin variants protect the inserted dyes and remarkably enhance their brightness. The albumin variants can also be genetically edited to develop size-tunable complexes with precisely tailored pharmacokinetics. The proteins can also be conjugated to biofunctional molecules without impacting the complexed dyes. This combination of albumin mutants and clinically-used cyanine dyes can help widen the clinical application prospects of NIR-II fluorophores.


Assuntos
Imagem Óptica , Quinolinas , Albuminas , Corantes Fluorescentes/química , Engenharia Genética , Ionóforos , Imagem Óptica/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...