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


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.

Mitofagia , Fotoquimioterapia , Mitocôndrias , Fármacos Fotossensibilizantes/farmacologia , Viscosidade
J Mater Chem B ; 9(4): 1018-1029, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33432955


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.

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
J Mater Chem B ; 8(36): 8323-8336, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32793936


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.

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
Chem Sci ; 11(37): 10279-10286, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34094292


Photodynamic therapy (PDT), as an emerging treatment modality, which takes advantage of reactive oxygen species (ROS) generated upon light illumination to ablate tumours, has suffered from a limited treatment depth, strong oxygen dependence and short ROS lifespan. Herein, we developed a highly efficient NIR-I light (808 nm laser) initiated theranostic system based on a fluorescent photosensitizer (EBD-1) with cancer cell membrane targeting ability, which can realize large penetration depth in tissue, generate superoxide radicals (O2 -˙) to relieve the oxygen-dependence, confine the ROS oxidation at the cell membrane, and self-report the cell viability during the PDT process. In vivo experiments demonstrated that EBD-1 under 808 nm light successfully accomplished remarkable cancer ablation. This work will be beneficial for the design of novel photosensitizers for PDT-based theranostic systems.