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1.
Anal Chim Acta ; 1178: 338847, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482880

RESUMO

Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.


Assuntos
Mitofagia , Fotoquimioterapia , Mitocôndrias , Fármacos Fotossensibilizantes/farmacologia , Viscosidade
2.
Anal Chem ; 93(35): 12059-12066, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34433261

RESUMO

Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform (CMTP-2) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.


Assuntos
Mitofagia , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Lisossomos , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Terapia Fototérmica
3.
J Mater Chem B ; 9(4): 1018-1029, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33432955

RESUMO

Recently, phototherapy has attracted much attention due to its negligible invasiveness, insignificant toxicity and excellent applicability. The construction of a newly proposed nanosystem with synergistic photothermal and photodynamic tumor-eliminating properties requires a delicate structure design. In this work, a novel therapeutic nanoplatform (denoted as BCS-Ce6) based on defective cobalt hydroxide nanosheets was developed, which realized hypoxia-relieved photothermal-enhanced photodynamic therapy against cancer. Defective cobalt hydroxide exhibited high photothermal conversion efficacy at the near-infrared region (49.49% at 808 nm) as well as enhanced catalase-like activity to produce oxygen and greatly boost the singlet oxygen generation by a photosensitizer, Ce6, realizing efficacious dual-modal phototherapy. In vivo and in vitro experiments revealed that BCS-Ce6 can almost completely extinguish implanted tumors in a mouse model and present satisfactory biocompatibility during the treatment. This work sets a new angle of preparing photothermal agents and constructing comprehensive therapeutic nanosystems with the ability to modulate the hypoxic tumor microenvironment for efficient cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Propriedades de Superfície , Tiazóis/química , Tiazóis/farmacologia , Elementos de Transição/química , Elementos de Transição/farmacologia , Células Tumorais Cultivadas
4.
J Mater Chem B ; 8(36): 8323-8336, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32793936

RESUMO

Exploiting two-dimensional nanomaterials as photo-based theranostic agents is promising for the highly efficient ablation of deep-tissue-buried tumors. However, they are limited by their poor absorption in the second near-infrared-light (NIR-II) bio-window (1000-1300 nm) and intrinsic nonbiodegradability. Herein, defect-rich sulfur-doped Ni(OH)2 (S-Ni(OH)2) nanosheets decorated with bovine serum albumin (BSA) as a novel theranostic agent is developed, which can accomplish multimodal-imaging-guided photothermal ablation of mouse cancers in the NIR-II bio-window. Sulfur doping extends the absorption spectra of Ni(OH)2 nanosheets from the visible to NIR-II bio-window, affording highly efficient photothermal conversion (58.20% for 1064 nm), entailing it to become an excellent contrast agent for photoacoustic imaging. Further, because of their intrinsic paramagnetic property, they can be applied for magnetic resonance imaging. Owing to the abundant defective sites in S-Ni(OH)2 nanosheets, they exhibit response to the tumor microenvironment, resulting in effective biodegradation and excretion from the body. In vivo toxicity experiments indicated that S-Ni(OH)2-BSA NSs delivered no appreciable toxicity and good biocompatibility. This work provides an avenue for the rational design of effective theranostics agents.


Assuntos
Antineoplásicos/uso terapêutico , Hidróxidos/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Níquel/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Bovinos , Feminino , Células HeLa , Humanos , Hidróxidos/química , Hidróxidos/farmacocinética , Hidróxidos/efeitos da radiação , Raios Infravermelhos , Camundongos Endogâmicos ICR , Imagem Multimodal , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Níquel/química , Níquel/farmacocinética , Níquel/efeitos da radiação , Terapia Fototérmica , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/uso terapêutico , Enxofre/química , Enxofre/farmacocinética , Enxofre/efeitos da radiação , Enxofre/uso terapêutico , Nanomedicina Teranóstica
5.
Anal Chem ; 92(15): 10815-10821, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32615754

RESUMO

Cell viability is greatly affected by external stimulus eliciting correlated dynamical physiological processes for cells to choose survival or death. A few fluorescent probes have been designed to detect whether the cell is in survival state or apoptotic state, but monitoring the regulation process of the cell undergoing survival to death remains a long-standing challenge. Herein, we highlight the in situ monitor of mitochondria regulating the cell viability by the RNA-specific fluorescent photosensitizer L. At normal conditions, L anchored mitochondria and interacted with mito-RNA to light up the mitochondria with red fluorescence. With external light stimulus, L generated reactive oxide species (ROS) and cause damage to mitochondria, which activated mitochondrial autophagy to prevent death, during which the red fluorescence of L witnessed dynamical distribution in accordance with the evolution of vacuole structures containing damaged mitochondria into autophagosomes. However, with ROS continuously increasing, the mitochondrial apoptosis was eventually commenced and L with red fluorescent was gradually accumulated in the nucleoli, indicating the programmed cell death. This work demonstrated how the delicate balance between survival and death are regulated by mitochondria.


Assuntos
Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/farmacologia , RNA/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células HeLa , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Modelos Moleculares , Conformação Molecular , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
6.
ACS Appl Mater Interfaces ; 12(2): 1988-1996, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31771326

RESUMO

Photodynamic therapy (PDT) takes advantage of reactive oxygen species (ROS) to trigger the apoptosis for cancer therapy. Given that cell apoptosis is a form of programmed cell death involved with multiple suborganelles and cancer cells are more sensitive to ROS than normal cells, early confirmation of the apoptosis induced by ROS would effectively avoid overtreatment. Herein, we highlight an aggregation-induced emission (AIE)-based theranostic agent (TPA3) to in situ dynamically track mitophagy prior to late apoptosis. TPA3 showed high specificity to autophagy vacuoles (AVs), of which appearance is the signature event of mitophagy during early apoptosis and delivered photocytotoxicity to cancer cells and skin cancer tumors in nude mice under irradiation of white light. Furthermore, in situ monitoring of the dynamical mitophagy process involved with mitochondria, AVs, and lysosomes was performed for the first time under confocal microscopy, providing a real-time self-monitoring system for assessing the curative effect prior to late apoptosis. This fluorescence imaging guided PDT witness great advances for applying in the clinical application.


Assuntos
Apoptose , Mitofagia , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Apoptose/efeitos da radiação , Autofagossomos/metabolismo , Autofagossomos/efeitos da radiação , Fluorescência , Células HeLa , Humanos , Lisossomos/metabolismo , Lisossomos/efeitos da radiação , Fusão de Membrana/efeitos da radiação , Camundongos Nus , Mitofagia/efeitos da radiação , Imagem Óptica , Espécies Reativas de Oxigênio/metabolismo , Tela Subcutânea/patologia
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