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1.
Front Bioeng Biotechnol ; 9: 780993, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805127

RESUMO

Phototheranostics have gained more and more attention in the field of cancer diagnosis and therapy. Among a variety of fluorophores for phototheranostics, semiconducting polymer nanoparticles (SPNs), which are usually constructed by encapsulating hydrophobic semiconducting polymers (SPs) with amphiphilic copolymers, have shown great promise. As second near-infrared (NIR-II) fluorescence imaging has both higher imaging resolution and deeper tissue penetration compared with first near-infrared (NIR-I) fluorescence imaging, NIR-II fluorescent SPNs have been widely designed and prepared. Among numerous structural units for semiconducting polymers (SPs) synthesis, thiadiazoloquinoxaline (TQ) has been proved as an efficient electron acceptor unit for constructing NIR-II fluorescent SPs by reacting with proper electron donor units. Herein, we summarize recent advances in TQ-based SPNs for NIR-II fluorescence imaging-guided cancer photothermal therapy. The preparation of TQ-based SPNs is first described. NIR-II fluorescence imaging-based and multimodal imaging-based phototheranostics are sequentially discussed. At last, the conclusion and future perspectives of this field are presented.

2.
ACS Appl Mater Interfaces ; 13(46): 54830-54839, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34767354

RESUMO

Well-designed second near-infrared (NIR-II) fluorophores are promising in optical diagnosis and therapy of tumors. In this work, we synthesized a donor-acceptor-donor (D-A-D) NIR-II fluorophore named BBTD-BET with dithienylethene as an electron donor and benzobisthiadiazole as an electron acceptor. To the best of our knowledge, this is the first report of using dithienylethene, a typical photochromic molecule, as a building block for NIR-II fluorophores. We studied the geometrical configuration, electronic state, and optical properties of BBTD-BET by both theoretical and experimental means. BBTD-BET had absorption and emission in the NIR-I and NIR-II spectral ranges, respectively. Using PEGylated BBTD-BET as a theranostic agent, we achieved NIR-II fluorescence/photoacoustic (PA) dual-modal imaging and attained high imaging resolution, desired signal-to-noise ratio, and excellent photothermal therapy (PTT) efficacy. After one PTT treatment, the tumors established in mice were eradicated. This work provides a novel organic conjugated molecule integrating NIR-II/PA dual-modal imaging and PTT functionalities that is very promising in the theranostic of tumors.

3.
Nat Commun ; 12(1): 6145, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686685

RESUMO

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.


Assuntos
Radical Hidroxila/metabolismo , Imagem Molecular/métodos , Sondas Moleculares/metabolismo , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Animais , Linhagem Celular Tumoral , Ferroptose , Fluorescência , Camundongos , Sondas Moleculares/química , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/radioterapia , Técnicas Fotoacústicas , Espectroscopia de Luz Próxima ao Infravermelho
4.
Chem Commun (Camb) ; 57(87): 11473-11476, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34652356

RESUMO

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we technically developed the metal-polyphenolic nanosystem with precise NIR-II fluorescence-imaging guidance for combining hafnium (Hf)-sensitized radiotherapy with PTT to regress tumor growth.

5.
Small ; 17(42): e2102527, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34528387

RESUMO

The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Fotoquimioterapia , Linhagem Celular Tumoral , Fluorescência , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Fototerapia , Nanomedicina Teranóstica , Termodinâmica , Microambiente Tumoral
6.
Biomater Sci ; 9(19): 6434-6443, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582525

RESUMO

Near-infrared II (NIR-II, 1000-1700 nm) fluorescent imaging (FI) has been reported to achieve optical images with higher resolution and deeper penetration. Among the organic NIR-II small molecules, donor-acceptor-donor (D-A-D) type fluorescent agents have shown superior photophysical and biocompatible properties for FI applications but have ongoing limitations, such as the difficulty in further modifying them with drug-carrying functional groups or prodrugs. In this work, three D-A-D type NIR-II fluorophores with electron acceptors of 4,8-bis(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-1H,3H-benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole) (BBT), 6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TTQ) and 4,6-bis(5-bromo-2-thienyl)thieno[3,4-c][1,2,5]thiadiazole (TTDT) have been successfully prepared. Their optical and imaging properties and stability were investigated via theoretical and experimental studies. The results demonstrated that TTDT-SF exhibited good NIR-II imaging ability. Importantly, TTDT-SF showed outstanding stability in an alkaline and redox environment. Subsequently, a stable atom transfer radical polymerization (ATRP) initiator, based on TTDT and its derivative water-soluble fluorescent polymer TTDT-TF-POEGMA, synthesized through ATRP, was successfully fabricated. It was demonstrated that TTDT-TF-POEGMA exhibited excellent fluorescence ability, great water solubility, effective light stability and great potential in tumor FI and image-guided surgery. In a word, this work has developed a new stable initiator with NIR-II fluorescent properties, which provides a platform for the development of water-soluble and multifunctional NIR-II fluorescent polymers for a broad range of applications.


Assuntos
Neoplasias , Polímeros , Corantes Fluorescentes , Humanos , Imagem Óptica , Polimerização
7.
Biosensors (Basel) ; 11(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34436084

RESUMO

As pH value almost affects the function of cells and organisms in all aspects, in biology, biochemical and many other research fields, it is necessary to apply simple, intuitive, sensitive, stable detection of pH and base characteristics inside and outside the cell. Therefore, many research groups have explored the design and application of pH probes based on surface enhanced Raman scattering (SERS). In this review article, we discussed the basic theoretical background of explaining the working mechanism of pH SERS sensors, and also briefly described the significance of cell pH measurement, and simply classified and summarized the factors that affected the performance of pH SERS probes. Some applications of pH probes based on surface enhanced Raman scattering in intracellular and extracellular pH imaging and the combination of other analytical detection techniques are described. Finally, the development prospect of this field is presented.


Assuntos
Concentração de Íons de Hidrogênio , Análise Espectral Raman , Humanos
8.
Biomaterials ; 275: 120916, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34091301

RESUMO

Fluorescence imaging (FI) in the second near-infrared region (NIR-II, 1000-1700 nm) has attracted great attention for brain tumor imaging due to its deep penetration and high resolution. However, traditional NIR-II organic fluorescent nanoparticles (NPs) are usually hindered by uncontrolled large size (~30-100 nm), marked aggregation-caused quenching (ACQ) effect, and limited blood circulation (~1-3 h), which have great impact on efficient NIR-II FI of deep brain tumors. Herein, starlike polymer brush-based ultrasmall TQFP-10 NPs, with bright NIR-II fluorescence, prolonged blood circulation, and enhanced tumor accumulation, are facilely prepared for efficient orthotopic glioblastoma (GBM) imaging. Compared with traditional method prepared NPs (physically coated TQF@NPs and PEG modified TQF-PEG5K NPs), the ultrasmall (~8 nm) TQFP-10 NPs display a higher NIR-II fluorescence QY (1.9%), which is 2.1- and 3.8-fold higher than TQF@NPs (0.9%) and TQF-PEG5K NPs (0.5%), respectively. In addition, TQFP-10 NPs present a 10.6-fold higher blood circulation half-life (t1/2 = 8.5 h) than that of TQF-PEG5K NPs. Consequently, TQFP-10 NPs exhibit 4.2- and 33-fold higher maximal tumor to normal tissue ratio in subcutaneous and in situ NIR-II FI of GBM, respectively, than TQF@NPs and TQF-PEG5K NPs, attractively realizing GBM imaging. This work provides a general strategy for constructing ultrasmall NIR-II fluorescent NPs with simultaneously improved NIR-II fluorescence and blood circulation for efficient brain tumor imaging.


Assuntos
Glioblastoma , Nanopartículas , Linhagem Celular Tumoral , Corantes Fluorescentes , Glioblastoma/diagnóstico por imagem , Humanos , Imagem Óptica , Polímeros
9.
Biomaterials ; 275: 120935, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34116284

RESUMO

Photothermal therapy (PTT) is hampered by limited light penetration depth and cell thermoresistance induced by over-expressed heat shock proteins (HSPs). Herein, we proposed a tumor-specific enhanced NIR-II PTT through the starvation mediated thermal sensitization strategy. A semiconducting polymer with superior NIR-II fluorescence imaging (FI) performance and NIR-II PTT efficacy was synthesized and encapsulated into folate modified liposomes, together with a glycolysis inhibitor, 2-deoxy-d-glucose (2DG). Upon specifically targeting folate receptors and guidance of NIR-II FI, spatiotemporal 2DG release could be achieved by the trigger of NIR-II photothermal effect. The released 2DG could not only deplete the energy supply of tumor cells by inhibiting tumor anaerobic glycolysis, but also decrease the ATP levels and hamper the production of HSPs, ultimately enhancing the tumor thermal sensitivity toward PTT. Owing to the sensitization effect of 2DG, tumor cells with overexpressed folate receptors could be significantly damaged by NIR-II PTT with an enhanced therapeutic efficiency. The work provided a promising strategy for specific starvation/NIR-II PTT synergistic therapy towards tumors.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagem Óptica , Fototerapia , Terapia Fototérmica , Polímeros
10.
Biomater Sci ; 9(9): 3499-3506, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949444

RESUMO

Nanotheranostics, which can provide great insight into cancer therapy, has been deemed as a promising technology to settle the unmet medical needs. The rational design of high performance nanotheranostics with multiple complementary imaging features and satisfactory therapeutic efficacy is particularly valuable. Herein, versatile nanotheranostic agents DPPB-Gd-I NPs were fabricated by using gadolinium-diethylenetriaminepentaacetic acid chelates and an iodine-decorated copolymer as encapsulation matrixes to encapsulate a polymer DPPB through one-step nanoprecipitation. We have demonstrated that such nanoagents are able to efficiently damage tumors under single dose injection and NIR laser illumination conditions due to the enhanced photodynamic therapy and enhanced photothermal therapy (the tumor inhibition rate was as high as 94.5%). Moreover, these nanoagents can be utilized as dual-modal NIR-II fluorescence/magnetic resonance imaging probes for tumor diagnosis with high sensitivity, deep tissue penetration, and excellent spatial resolution. Overall, this work offers a powerful tactic to fabricate high performance nanotheranostics for clinical application.


Assuntos
Fotoquimioterapia , Nanomedicina Teranóstica , Fluorescência , Imageamento por Ressonância Magnética , Fototerapia
11.
Adv Mater ; 33(22): e2008481, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33899283

RESUMO

Photothermal therapy (PTT), one of the most-potent cancer therapeutic strategies known, is highlighted with excessive inflammatory response, while ablating cancer with immunogenic death. This hyperactive immune response may override PTT-triggered immunogenicity, exacerbate skin empyrosis, and incur permanent tissue injury and high-profile tumor regeneration. Therefore, an anticancer balance between pathological and protective immune response is urgently needed for an advanced photothermal therapeutic tactic. Herein, a gas-modulated photothermal immunogenicity strategy is proposed by integrating an amphiphilic-conjugated polymer with a polysulfide-based hydrogen sulfide (H2 S) donor (2,2'-dipyridyl tetrasulfide@CP-PEG) (where CP = conjugated polymer and PEG = poly(ethylene glycol)). The CP is endowed with NIR-II fluorescence capacity and favorable photothermal effect, tracing the tumor for precise therapeutics. The polysulfide donor can release H2 S triggered by intracellular glutathione, which elicits mitochondrial dysfunction and robust anti-inflammation effect. Ultimately, this gas-modulated PTT strategy inhibits tumor growth remarkably and limits the magnitude of PTT-induced proinflammatory tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß) cytokines. Moreover, the regulated inflammation accelerates PTT-induced wound healing. A H2 S-modulated PTT with adaptive immune response is thus recommended as an advanced strategy to cancer therapeutics.


Assuntos
Sulfeto de Hidrogênio , Animais , Linhagem Celular Tumoral , Terapia Combinada , Neoplasias
12.
Small ; 17(12): e2007566, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33666345

RESUMO

Organic theranostic nanomedicine has precision multimodel imaging capability and concurrent therapeutics under noninvasive imaging guidance. However, the rational design of desirable multifunctional organic theranostics for cancer remains challenging. Rational engineering of organic semiconducting nanomaterials has revealed great potential for cancer theranostics largely owing to their intrinsic diversified biophotonics, easy fabrication of multimodel imaging platform, and desirable biocompatibility. Herein, a novel all-organic nanotheranostic platform (TPATQ-PNP NPs) is developed by exploiting the self-assembly of a semiconducting small molecule (TPATQ) and a new synthetic high-density nitroxide radical-based amphiphilic polymer (PNP). The nitroxide radicals act as metal-free magnetic resonance imaging agent through shortened longitudinal relaxation times, and the semiconducting molecules enable ultralow background second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging. The as-prepared TPATQ-PNP NPs can light up whole blood vessels of mice and show precision tumor-locating ability with synergistic (MR/NIR-II) imaging modalities. The semiconducting molecules also undergo highly effective photothermal conversion in the NIR region for cancer photothermal therapy guided by complementary tumor diagnosis. The designed multifunctional organic semiconducting self-assembly provides new insights into the development of a new platform for cancer theranostics.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Animais , Imageamento por Ressonância Magnética , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Polímeros , Nanomedicina Teranóstica
13.
Nanoscale Horiz ; 6(2): 177-185, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33443277

RESUMO

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor" structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.


Assuntos
Antineoplásicos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Tiofenos/uso terapêutico , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Multimodal/métodos , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Medicina de Precisão/métodos , Tiofenos/síntese química , Tiofenos/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Mater Chem B ; 9(4): 1002-1008, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33399620

RESUMO

Single-component nanoplatforms combined with the second near-infrared optical window (NIR-II, 1000-1700 nm) fluorescence imaging (FI) and NIR-II photothermal therapy (PTT) have received increasing attention owing to their capacity for precise diagnosis, noninvasive therapy, and real-time monitoring of the therapeutic effects. However, most of the PTT treatments are performed in the NIR-I window (700-900 nm). Moreover, the design and development of conjugated polymers (P1, P2, and P3) with both bright NIR-II fluorescence and superior NIR-II photothermal effect remained a huge challenge. Therefore, three double-acceptor conjugated polymers were designed and developed by adjusting the molar ratios of two acceptors, TTQ and DPP. Subsequently, their corresponding nanoparticles were fabricated, and finally, nanoparticles based on the conjugated polymer P1 (P1 NPs) with both high NIR-II fluorescence intensity and superior NIR-II photothermal efficiency were selected and applied for NIR-II FI and NIR-II PTT. Importantly, the experiments of in vivo NIR-II FI and NIR-II PTT demonstrated that P1 NPs exhibited not only high accumulation in the tumour sites and high sign-to-background ratio (SBR) of vascular imaging, but also superior NIR-II PTT efficiency for tumour treatment.


Assuntos
Corantes Fluorescentes/farmacologia , Imagem Óptica , Terapia Fototérmica , Polímeros/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/química , Hipertermia Induzida , Raios Infravermelhos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
15.
Nat Commun ; 11(1): 6183, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273452

RESUMO

NIR-II fluorophores have shown great promise for biomedical applications with superior in vivo optical properties. To date, few small-molecule NIR-II fluorophores have been discovered with donor-acceptor-donor (D-A-D) or symmetrical structures, and upconversion-mitochondria-targeted NIR-II dyes have not been reported. Herein, we report development of D-A type thiopyrylium-based NIR-II fluorophores with frequency upconversion luminescence (FUCL) at ~580 nm upon excitation at ~850 nm. H4-PEG-PT can not only quickly and effectively image mitochondria in live or fixed osteosarcoma cells with subcellular resolution at 1 nM, but also efficiently convert optical energy into heat, achieving mitochondria-targeted photothermal cancer therapy without ROS effects. H4-PEG-PT has been further evaluated in vivo and exhibited strong tumor uptake, specific NIR-II signals with high spatial and temporal resolution, and remarkable NIR-II image-guided photothermal therapy. This report presents the first D-A type thiopyrylium NIR-II theranostics for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and excellent photothermal efficiency.


Assuntos
Corantes Fluorescentes/química , Raios Infravermelhos , Mitocôndrias/metabolismo , Neoplasias/diagnóstico por imagem , Imagem Óptica , Terapia Fototérmica , Animais , Morte Celular , Durapatita/química , Corantes Fluorescentes/síntese química , Luminescência , Camundongos Nus , Conformação Molecular , Polietilenoglicóis/química , Espectrometria de Fluorescência , Resultado do Tratamento
16.
Artigo em Inglês | MEDLINE | ID: mdl-33205657

RESUMO

The development of effective and safe tumor nanotheranostics remains a research imperative. Herein, tumor microenvironment (TME)-responsive Fe(III)-porphyrin (TCPP) coordination nanoparticles (FT@HA NPs) were prepared using a simple one-pot method followed by modification with hyaluronic acid (HA). FT@HA NPs specifically accumulated in CD44 receptor-overexpressed tumor tissues through the targeting property of HA and upon endocytosis by tumor cells. After cell internalization, intracellular acidic microenvironments and high levels of glutathione (GSH) triggered the rapid decomposition of FT@HA NPs to release free TCPP molecules and Fe(III) ions. The released Fe(III) ions could trigger GSH depletion and Fenton reaction, activating chemodynamic therapy (CDT). Meanwhile, the fluorescence and photodynamic effects of the TCPP could be also activated, achieving controlled reactive oxygen species (ROS) generation and avoiding side effects on normal tissues. Moreover, the rapid consumption of GSH further enhanced the efficacy of CDT and photodynamic therapy (PDT). The in vivo experiments further demonstrated that the antitumor effect of these nanotheranostics was significantly enhanced and that their toxicity and side effects against normal tissues were effectively suppressed. The FT@HA NPs can be applied for activated tumor combination therapy under the guidance of dual-mode imaging including fluorescence imaging and magnetic resonance imaging, providing an effective strategy for the design and preparation of TME-responsive multifunctional nanotheranostics for precise tumor imaging and combination therapy.

17.
J Mater Chem B ; 8(43): 9933-9942, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33034312

RESUMO

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.


Assuntos
Glucose Oxidase/uso terapêutico , Peróxido de Hidrogênio/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Cério/uso terapêutico , Feminino , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos
18.
ACS Appl Mater Interfaces ; 12(39): 43466-43473, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32907323

RESUMO

Aggregation-induced emission (AIE) fluorophores with second near-infrared window (NIR-II) fluorescence are very promising for in vivo imaging because they emit fluorescence in an aggregated state and provide desirable imaging resolution and depth. Up to now, only a limited number of NIR-II AIE fluorophores have been developed. Therefore, synthesizing novel NIR-II AIE fluorophores and investigating structural effects on their photophysical properties are very important for the development of AIE probes. In this work, we synthesized two donor-acceptor-donor-type NIR fluorophores with emissions extending into the NIR-II window named DPTQ-PhPTZ and DPTQ-PhPXZ with phenothiazine (PTZ) and phenoxazine (PXZ) derivatives as the electron donors, respectively, and studied their photophysical properties via theoretical and experimental approaches as well as the properties in NIR-II in vivo imaging. The PTZ and PXZ moieties provided typical AIE characteristics. Despite the very similar chemical structures of PTZ and PXZ, DPTQ-PhPTZ and DPTQ-PhPXZ exhibited rather different photophysical properties, for example, compared to DPTQ-PhPTZ, DPTQ-PhPXZ had higher quantum yield (QY) both in solution and in the aggregated state and its QY was less sensitive to solvent polarity. After being coated with an amphiphilic copolymer F-127, the fluorophores maintained fluorescence, and the formed fluorescent polymer nanoparticles (NPs) had satisfactory tumor accumulation and biocompatibility, implying that they are applicable for in vivo tumor detection.


Assuntos
Corantes Fluorescentes/química , Oxazinas/química , Fenotiazinas/química , Fluorescência , Raios Infravermelhos , Estrutura Molecular , Nanopartículas/química , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície
19.
Chem Soc Rev ; 49(21): 7533-7567, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-32996497

RESUMO

Boron-dipyrromethene (BODIPY) belongs to a family of organoboron compounds, commercialized as fluorescent dyes by Invitrogen™. As BODIPY derivatives, Aza-boron-dipyrromethene (Aza-BODIPY) dyes display superior spectral performances, such as red-shifted spectra and high molar extinction coefficients, and are considered to be extremely attractive organic materials for various bioapplications. Therefore, scientists from different disciplinary backgrounds would benefit from a review that provides a timely summary and outlook regarding Aza-BODIPY dyes. In this review, we report on the latest advances of Aza-BODIPY dyes, along with the empirical design guidelines and photophysical property manipulation of these dyes. In addition, we will discuss the biological applications of Aza-BODIPY dyes in probing various biological activities, as well as in fluorescence bioimaging/detection, newly-emerging photoacoustic bioimaging/detection, and phototherapy together with future challenges and implications in this field. We aim at providing an insightful design guideline and a clear overview of Aza-BODIPY dyes, which might entice new ideas and directions.


Assuntos
Compostos Aza/química , Compostos de Boro/química , Corantes Fluorescentes/química , Imagem Óptica , Técnicas Fotoacústicas , Compostos de Boro/síntese química , Corantes Fluorescentes/síntese química
20.
Small ; 16(39): e2002939, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32875678

RESUMO

The incidence of triple-negative breast cancer (TNBC) is difficult to predict, and TNBC has a high mortality rate among women worldwide. In this study, a theranostics approach is developed for TNBC with ratiometric photoacoustic monitored thiol-initiated hydrogen sulfide (H2 S) therapy. The ratiometric photoacoustic (PA) probe (CY) with a thiol-initiated H2 S donor (PSD) to form a nanosystem (CY-PSD nanoparticles) is integrated. In this theranostics approach, H2 S generated from PSD is sensed by CY based on ratiometric PA signals, which simultaneously pinpoints the tumor region. Additionally, H2 S is cytotoxic toward TNBC cells (MDA-MB 231), showing a tumor inhibition rate of 63%. To further verify its pharmacological mechanism, proteomics analysis is performed on tumors treated with CY-PSD nanoparticles. Cells are killed by the significant mitochondrial dysfunction via supressed energy supply and apoptosis initiation. Besides, the observed inhibition of oxidative stress also generates the cytotoxicity. Significant Kyoto Encyclopedia of Genes Genomes pathways related to TNBC are found to be inhibited. This H2 S theranostics approach updates the current anticancer therapies which brings promise for women suffering malignant breast cancer.


Assuntos
Antineoplásicos , Técnicas Fotoacústicas , Medicina de Precisão , Sulfetos , Neoplasias de Mama Triplo Negativas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Medicina de Precisão/instrumentação , Sulfetos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral
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