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1.
Adv Mater ; : e2109036, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990517

RESUMO

Combination therapy is a promising approach for effective treatment of tumors through synergistically regulating pathways. However, the synergistic effect is limited, likely by uncontrolled co-delivery of different therapeutic payloads in a single nanoparticle. Herein, we developed a combination nanotherapeutic by using two amphiphilic conjugates hyperbranched poly(ethylene glycol)-pyropheophorbide-a (Ppa) (HP-P) and hyperbranched poly(ethylene glycol)-doxorubicin (DOX) (HP-D) to construct co-assembly nanoparticles (HP-PD NPs) for controllably co-loading and co-delivering Ppa and DOX. In vitro and in vivo anti-tumor studies confirmed the synergistic effect of photodynamic therapy and chemotherapy from HP-PD NPs. Metabolic variations revealed that tumor suppression was associated with disruption of metabolic homeostasis, leading to reduced protein translation. Our study uncovers the manipulation of metabolic changes in tumor cells through disruption of cellular homeostasis using HP-PD NPs and provides a new insight into rational design of synergistic nanotherapeutics for combination therapy. This article is protected by copyright. All rights reserved.

2.
Adv Mater ; : e2108049, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875724

RESUMO

Linear-dendritic block copolymer (LDBCs) are highly attractive candidates for smart drug delivery vehicles. Herein, we report an amphiphilic poly[(ethylene glycol) methyl ether methacrylate] (POEGMA) linear-peptide dendritic prodrug of doxorubicin (DOX) prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. A hydrophobic dye-based photosensitizer chlorin e6 (Ce6) was employed for encapsulation in the prodrug nanoparticles (NPs) to obtain a LDBCs-based drug delivery system (LD-DOX/Ce6) which offered a combination cancer therapy. Due to the presence of Gly-Phe-Leu-Gly peptides and hydrazone bonds in the prodrug structure, LD-DOX/Ce6 were degraded into small fragments, thus specifically triggering the intracellular release of DOX and Ce6 in the tumor microenvironment. Bioinformatics analysis suggested that LD-DOX/Ce6 with laser irradiation treatment significantly induced apoptosis, DNA damage and cell cycle arrest. The combination treatment could not only suppress tumor growth, but also significantly reduced tumor metastasis compared with treatments with DOX or Ce6 through regulating EMT pathway, TGFß pathway, angiogenesis and the hypoxia pathway. LD-DOX/Ce6 displayed a synergistic chemo-photodynamic anti-tumor efficacy, resulting in a high inhibition in tumor growth and metastasis, while maintaining an excellent biosafety. Therefore, this study has demonstrated potential of the biodegradable and tumor microenvironment-responsive LDBCs as an intelligent multifunctional drug delivery vehicle for high-efficiency cancer combination therapy. This article is protected by copyright. All rights reserved.

3.
Analyst ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821886

RESUMO

Lipid droplets (LDs) are dynamic multifunctional organelles that participate in the regulation of many metabolic processes, visualization of which is necessary for biological research. In this work, a series of two-photon responsive fluorescent probes (C-H, C-Br, and C-I) based on carbazole units were designed and synthesized. Thereinto, an iodine-modified carbazole derivative C-I exhibited an exciting lipid droplet targeting ability due to its excellent lipophilicity. Meanwhile, benefiting from its larger Stokes shift and two-photon absorption cross-section, C-I was employed for two-photon confocal laser scanning microscopy (CLSM) and stimulated emission depletion (STED) microscopy imaging to observe LDs more accurately. In addition, given the heavy atom effect, C-I can effectively generate reactive oxygen species (ROS) leading to cancer cell apoptosis under near-infrared light irradiation. Notably, we explained the process of cell apoptosis through in vitro simulation experiments. This study provides a promising platform for visualization of lipid droplets.

4.
BMJ Open ; 11(10): e051761, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663665

RESUMO

INTRODUCTION: Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes mellitus. Guidelines for DR screening in different countries vary greatly, including fundus photography, slit-lamp biomicroscopy, indirect ophthalmoscopy, Optical Coherence Tomography (OCT), OCT-A and Fundus Fluorescein Angiography (FFA). Two-field non-mydriatic fundus photography (NMFP) is an effective screening method due to its low cost and less time-consuming process. However, it is controversial due to the sensitivity and specificity of two-field NMFP. This review intends to evaluate the performance of the two-field NMFP in diagnosing DR and helps clinicians determine the most optimal screening method. METHODS AND ANALYSIS: Two reviewers will independently search on the Medline, Embase, Cochrane databases, ProQuest, Opengrey, Chinese National Knowledge Infrastructure, Wanfang Data, VIP China Science and Technology Journal Database, Chinese BioMedical Literature Database, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to identify relevant studies. There is no restriction posed on the language of the study. Included studies focus on the performance of two-field NMFP in detecting DR in diabetes patients. Analysis and evaluation of the studies will be examined by two reviewers independently using the Quality Assessment for Diagnostic Accuracy Studies-2 tool and later evaluated using the Population, Intervention, Comparison, Outcome, Study design criteria. A random-effect model will calculate the diagnostic indicators, including the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR, area under the curve and 95% CIs. We will also develop a summary receiver operating characteristic curve. We anticipate analysing subgroups according to the factors, which may lead to heterogeneity, including DR levels of patients, the reference standards, camera models, the interpretation criteria. The data will be analysed by STATA software. This study was registered with PROSPERO. ETHICS AND DISSEMINATION: This review will analyse the published data. Patients/the public were not involved in this research. The results of this study will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020203608.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Retinopatia Diabética/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Humanos , Metanálise como Assunto , Fotografação , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto
5.
Front Oncol ; 11: 752725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707994

RESUMO

Targeted therapies such as oral tyrosine kinase inhibitors (TKIs) are the main therapeutic strategy effective for advanced hepatocellular carcinoma (HCC). Currently six tyrosine kinase inhibitors for HCC therapy have been approved. The newly approved first-line drug donafenib represent the major milestones in HCC therapeutics in recent years. However, drug resistance in HCC remains challenging due to random mutations in target receptors as well as downstream pathways. TKIs-based combinatorial therapies with immune checkpoint inhibitors such as PD-1/PD-L1 antibodies afford a promising strategy to further clinical application. Recent developments of nanoparticle-based TKI delivery techniques improve drug absorption and bioavailability, enhance efficient targeting delivery, prolonged circulation time, and reduce harmful side effects on normal tissues, which may improve the therapeutic efficacy of the TKIs. In this review, we summarize the milestones and recent progress in clinical trials of TKIs for HCC therapy. We also provide an overview of the novel nanoparticle-based TKI delivery techniques that enable efficient therapy.

6.
ACS Sens ; 6(11): 3978-3984, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34498846

RESUMO

Histones are the alkali proteins in eukaryotic somatic chromatin cells which constitute the nucleosome structure together with DNA. Their abnormality is often associated with multiple tumorigenesis and other human diseases. Nevertheless, a simple and efficient super-resolution method to visualize histone distribution at the subcellular level is still unavailable. Herein, a Zn(II) terpyridine complex with rich-electronic azide units, namely, TpZnA-His, was designed and synthesized. The initial in vitro and in silico studies suggested that this complex is able to detect histones rapidly and selectively via charge-charge interactions with the histone H3 subunit. Its live cell nuclear localization, red-emission tail, and large Stokes shift allowed super-resolution evaluation of histone distributions with a clear distinction against nuclear DNA. We were able to quantitatively conclude three histone morphology alternations in live cells including condensation, aggregation, and cavity during activating histone acetylation. This work offers a better understanding as well as a versatile tool to study histone-involved gene transcription, signal transduction, and differentiation in cells.

7.
Anal Chem ; 93(40): 13667-13672, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34591458

RESUMO

Understanding signaling molecules in regulating organelles dynamics and programmed cell death is critical for embryo development but is also challenging because current imaging probes are incapable of simultaneously imaging the signaling molecules and the intracellular organelles they interact with. Here, we report a chemically and environmentally dual-responsive imaging probe that can react with gasotransmitters and label cell nuclei in distinctive fluorescent colors, similar to the adaptive coloration of chameleons. Using this intracellular chameleon-like probe in three-dimensional (3D) super-resolution dynamic imaging of live cells, we discovered SO2 as a critical upstream signaling molecule that activates nucleophagy in programmed cell death. An elevated level of SO2 prompts kiss fusion between the lysosomal and nuclear membranes and nucleus shrinkage and rupture. Significantly, we revealed that the gasotransmitter SO2 is majorly generated in the yolk, induces autophagy there at the initial stage of embryo development, and is highly related to the development of the auditory nervous system.


Assuntos
Corantes Fluorescentes , Dióxido de Enxofre , Autofagia , Núcleo Celular , Desenvolvimento Embrionário , Células HeLa , Humanos
8.
Adv Mater ; 33(45): e2104594, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34554623

RESUMO

Inspired by natural saccharide-protein complexes, a stimuli-responsive biodegradable and branched glycopolymer-pyropheophorbide-a (Ppa) conjugate (BSP) with saccharide units for cancer therapy is constructed. A linear glycopolymeric conjugate (LSP), a branched glycopolymeric conjugate (BShP) from Ppa with long carbon chains, and a branched conjugate (BHSP) based on poly[N-(2-hydroxypropyl) methacrylamide] (polyHPMA) without saccharide units are prepared as controls. Through structure-activity relationship studies, BSP with a 3D network structure forms stable nanostructures via weak intermolecular interactions, regulating the stacking state of Ppa to improve the singlet oxygen quantum yield and the corresponding photodynamic therapy (PDT) effect. BSP shows high loading of olaparib, and are further coated with tumor cell membranes, resulting in a biomimetic nanomedicine (CM-BSPO). CM-BSPO shows highly efficient tumor targeting and cellular internalization properties. The engulfment of CM-BSPO accompanied with laser irradiation results in a prominent antitumor effect, evidenced by disruption of cell cycles in tumor cells, increased apoptosis and DNA damage, and subsequent inhibition of repair for damaged DNA. The mechanism for the synergistic effect from PDT and olaparib is unveiled at the genetic and protein level through transcriptome analysis. Overall, this biodegradable and branched glycopolymer-drug conjugate could be effectively optimized as a biomimetic nanomedicine for cancer therapy.

9.
J Nanobiotechnology ; 19(1): 244, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391417

RESUMO

BACKGROUND: Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. RESULTS: Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r1 = 0.93 mM- 1 s- 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. CONCLUSIONS: Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application.

10.
Talanta ; 234: 122639, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364448

RESUMO

Three-photon absorption (3 PA) in the near IR region is among the most prominent nonlinear optical (NLO) effects and has attractive applications in chemical/biological sensing and imaging. Yet, rationally constructed molecules with small molecular weight and reasonable 3 PA cross-section has been rarely reported. Herein, we designed a novel three-photon absorption photostable luminogen (namely X1) with enhanced aggregation induced emission (AIE) and the ability to achieve multi-photon imaging with femtosecond laser excitation. X1 was constructed from diaminobenzene and diethylamino salicylaldehyde forming a novel di-Schiff base. It possesses a large conjugated delocalization which exhibits large three-photon absorption (3 PA) cross-section values. We also showed that by using a suitable delivery vector, X1 compound could applied as a live cell imaging probe thus providing a valuable tool to study lipid droplets/lysosome interaction in depth tissues.


Assuntos
Corantes Fluorescentes , Fótons , Microscopia de Fluorescência , Bases de Schiff
11.
Front Bioeng Biotechnol ; 9: 653800, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095096

RESUMO

Secondary metabolites of traditional Chinese herbs can prominently stimulate the production of laccase from white rot fungi during submerged fermentation. However, the molecular mechanism through which these natural products induce the production of laccase remains unknown. In this study, the Chinese herbal medicine Polygonum cuspidatum was used to induce laccase production in Trametes versicolor, and the best inducer was identified in emodin, even under conditions of 1000-L, large-scale fermentation. Proteomics analysis identified a selection of proteins that were differentially expressed in the presence of emodin, indicating that emodin may affect the expression of laccase genes through three mechanisms: reducing bioenergy productivity, the aryl hydrocarbon receptor (AHR)/xenobiotic response element (XRE) pathway, and the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. Combined with protoplast flow cytometry and fluorescence, it is revealed that emodin might reduce the synthesis of ATP by lowering the mitochondrial membrane potential, leading to the subsequent responses.

12.
Chem Commun (Camb) ; 57(54): 6628-6631, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34124718

RESUMO

A ratiometric fluorescent probe with a large emission shift was developed for the accurate measurement of hydrogen peroxide (H2O2) in sophisticated pyroptosis signaling pathways. The results reported here demonstrate that H2O2, as a principal member of ROS, is a critical upstream signaling molecule in regulating pyroptosis.


Assuntos
Corantes Fluorescentes/metabolismo , Peróxido de Hidrogênio/metabolismo , Piroptose , Transdução de Sinais , Linhagem Celular , Sobrevivência Celular , Humanos
13.
Anal Methods ; 13(28): 3181-3186, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34169932

RESUMO

Mitochondrial matrix contains numerous metabolism-related proteins/enzymes and nucleic acids, which play key roles in the process of energy generation and signal transduction. The fluctuations in mitochondrial biomacromolecular levels lead to the changes in the mitochondrial matrix viscosity; therefore, real-time measuring the mitochondrial matrix viscosity is of great significance for the in-depth understanding of the mitochondrial physiology and pathobiology. However, investigations are limited due to the lack of a mitochondrial matrix-specific molecular rotor. Herein, we report a design of a molecular rotor that is specifically enriched in the mitochondrial matrix. The red fluorescence of the rotor switches on when the viscosity increases, enabling the real-time monitoring of the viscosity change therein. Interestingly, the rotor showed non-fluorescence behaviour in the liposome (mimicking membrane structure), avoiding fluorescence interference from the mitochondrial bilayer membrane. Super-resolution imaging reveals that the viscosity is uneven in an individual mitochondrion.


Assuntos
Corantes Fluorescentes , Mitocôndrias , Diagnóstico por Imagem , Fluorescência , Viscosidade
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 260: 119923, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015744

RESUMO

Compared to general fluorescent dyes, multi-photon fluorescent dyes exhibit deeper tissue penetration and lower auto-fluorescence in the bio-imaging field. Therefore, it is necessary to develop an efficient multiphoton imaging agent for deep tissue imaging. In this work, an organotin derivative (HSnBu3) has been designed and synthesized, which shows multiphoton absorption activity. In constrast to the ignorable three-photon activity of the ligand, the complex (HSnBu3) exhibits three-photon activity under NIR excitation (1500 nm). Results of chemical and biological tests confirmed that HSnBu3 was more easily activated by oxygen resulting in a higher level of 1O2, which could induce a decrease in mitochondrial membrane potential in HepG2 cells. It suggests that HSnBu3 has potential in photodynamic therapy.


Assuntos
Fotoquimioterapia , Fótons , Diagnóstico por Imagem , Corantes Fluorescentes , Espécies Reativas de Oxigênio
15.
Cell Death Dis ; 12(3): 251, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674562

RESUMO

Ciclopirox (CPX) is an antifungal drug that has recently been reported to act as a potential anticancer drug. However, the effects and underlying molecular mechanisms of CPX on glioblastoma multiforme (GBM) remain unknown. Bortezomib (BTZ) is the first proteasome inhibitor-based anticancer drug approved to treat multiple myeloma and mantle cell lymphoma, as BTZ exhibits toxic effects on diverse tumor cells. Herein, we show that CPX displays strong anti-tumorigenic activity on GBM. Mechanistically, CPX inhibits GBM cellular migration and invasion by reducing N-Cadherin, MMP9 and Snail expression. Further analysis revealed that CPX suppresses the expression of several key subunits of mitochondrial enzyme complex, thus leading to the disruption of mitochondrial oxidative phosphorylation (OXPHOS) in GBM cells. In combination with BTZ, CPX promotes apoptosis in GBM cells through the induction of reactive oxygen species (ROS)-mediated c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling. Moreover, CPX and BTZ synergistically activates nuclear factor kappa B (NF-κB) signaling and induces cellular senescence. Our findings suggest that a combination of CPX and BTZ may serve as a novel therapeutic strategy to enhance the anticancer activity of CPX against GBM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bortezomib/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Ciclopirox/farmacologia , Glioblastoma/tratamento farmacológico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Glioblastoma/enzimologia , Glioblastoma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fosforilação Oxidativa/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
ACS Appl Mater Interfaces ; 13(8): 9739-9747, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33617221

RESUMO

The exploitation of effective strategies to develop materials bearing deep tissue focal fluorescence imaging capacity and excellent reactive oxygen species (ROS) generation ability is of great interest to address the high-priority demand of photodynamic therapy (PDT). Therefore, we use a rational strategy to fabricate a two-photon-active metal-organic framework via a click reaction (PCN-58-Ps). Moreover, PCN-58-Ps is capped with hyaluronic acid through coordination to obtain cancer cell-specific targeting properties. As a result, the optimized composite PCN-58-Ps-HA exhibits considerable two-photon activity (upon laser excitation at a wavelength of 910 nm) and excellent light-triggered ROS (1O2 and O2•-) generation ability. In summary, the interplay of these two critical factors within the PCN-58-Ps-HA framework gives rise to near-infrared light-activated two-photon PDT for deep tissue cancer imaging and treatment, which has great potential for future clinical applications.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Benzotiazóis/síntese química , Benzotiazóis/farmacologia , Benzotiazóis/efeitos da radiação , Química Click , Células HEK293 , Células HeLa , Humanos , Ácido Hialurônico/análogos & derivados , Ácido Hialurônico/farmacologia , Ácido Hialurônico/efeitos da radiação , Raios Infravermelhos , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/efeitos da radiação , Fotoquimioterapia , Fótons , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
17.
Biosens Bioelectron ; 178: 113036, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33548656

RESUMO

Recent advancements in super-resolution nanoscopy allowed the study of mitochondrial biology at nanoscale and boosted the understanding its correlated cellular processes those were previously poorly understood. Nevertheless, studying mitochondrial ultrastructure remains a challenge due to the lack of probes that could target specific mitochondrial substances (e.g. cristae or mtDNA) and survive under harsh super-resolution optical conditions. Herein, in this work, we have rationally constructed a pyridine-BODIPY (Py-BODIPY) derivative that could target mitochondrial membrane in living cells without interfering its physiological microenvironments. Furthermore, we found Py-BODIPY is a membrane potential independent probe, hence it is not limit to live-cell staining but also showed a strong internalization into pre-fixed and stimulus disrupted sample. Importantly, its cristae specificity and superb photostability allow the observation of mitochondrial dynamic nano-structures with an unprecedented resolution, allow demonstrating how mitochondrial 3D ultrastructure evolved under oxidative phosphorylation condition.


Assuntos
Técnicas Biossensoriais , Dinâmica Mitocondrial , Compostos de Boro , Humanos , Fosforilação Oxidativa , Piridinas
18.
Inorg Chem ; 60(4): 2362-2371, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33494602

RESUMO

Multiphoton materials are in special demand in the field of photodynamic therapy and multiphoton fluorescence imaging. However, rational design methodology for these brands of materials is still nascent. This is despite transition-metal complexes favoring optimized nonlinear-optical (NLO) activity and heavy-atom-effected phosphorescent emission. Here, three four-photon absorption (4PA) platinum(II) complexes (Pt1-Pt3) are achieved by the incorporation of varied functionalized C^N^C ligands with high yields. Pt1-Pt3 exhibit triplet metal-to-ligand charge-transfer transitions at ∼460 nm, which are verified multiple times by transient absorption spectra, time-dependent density functional theory calculations, and low-temperature emission spectra. Further, Pt1-Pt3 undergo 4PA. Notably, one of the complexes, Pt2, has maximum 4PA cross-sectional values of up to 15.2 × 10-82 cm8 s3 photon-3 under excitation of a 1600 nm femtosecond laser (near-IR II window). The 4PA cross sections vary when Pt2 is binding to lecithin and when it displays its lysosome-specific targeting behavior. On the basis of the excellent 4PA property of Pt2, we believe that those 4PA platinum(II) complexes have great potential applications in cancer theranostics.


Assuntos
Antineoplásicos/química , Antineoplásicos/uso terapêutico , Complexos de Coordenação/química , Lisossomos/efeitos dos fármacos , Compostos de Platina/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Humanos , Camundongos , Fótons , Compostos de Platina/farmacologia , Compostos de Platina/uso terapêutico , Análise Espectral/métodos , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Adv Healthc Mater ; 10(7): e2001489, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33336561

RESUMO

Multi-photon photosensitizers (PSs) could significantly improve the efficacy of photodynamic therapy due to the long-wavelength favorability for deeper tissue penetration and lower biological damage. However, most studies are limited to single-photon or two-photon PSs at a relatively short-wave excitation window. To overcome this barrier, we rationally design a series of rigid plane compounds with efficient reactive oxygen species (ROS) production in vitro under laser irradiation. Furthermore, the studies show that one of the compounds (U-TsO) could induce rapid multi-types of cell death under three-photon exposure, suggesting a promising clinical outcome in ex vivo 3D multicellular tumor spheroid. This work offers a novel strategy to construct functional materials with competitive multi-photon photodynamic therapy (PDT) outcome.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Morte Celular , Fótons , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio
20.
Analyst ; 145(24): 7941-7945, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33030164

RESUMO

Compared to general fluorescent probes, multi-photon fluorescent probes exhibit deeper tissue penetration, lower auto-fluorescence and lower photo-toxicity in the bio-imaging field. Herein, we synthesized a series multi-photon fluorescent probe (L1-L3) based on quinolone groups. Of notably, the three-photon fluorescence of L3 significantly enhanced when L3 interacted with liposome; moreover, L3 exhibited high selectivity towards lipid droplets in living cells. Due to its large Stokes shift, high selectivity and photon-stability, L3 was successfully used in lipid droplet imaging via multi-photon fluorescence bio-imaging.


Assuntos
Corantes Fluorescentes , Quinolinas , Células HeLa , Humanos , Gotículas Lipídicas , Fótons
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