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1.
Sci Bull (Beijing) ; 69(9): 1263-1274, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38418300

RESUMEN

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy-D-glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000-1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system.


Asunto(s)
Clorofilidas , Glucosa , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfirinas , Fotoquimioterapia/métodos , Humanos , Animales , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/farmacología , Porfirinas/uso terapéutico , Glucosa/metabolismo , Nanopartículas/uso terapéutico , Desoxiglucosa/farmacología , Ratones , Rayos Infrarrojos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/diagnóstico por imagen , Hexoquinasa/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Glucólisis/efectos de los fármacos , Reprogramación Metabólica
2.
Signal Transduct Target Ther ; 8(1): 277, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37474504

RESUMEN

The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing technology. Several intratumoral bacteria which have been identified as pathogens of cancer that induce progression, metastasis, and poor outcome of cancer, while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens localization. Thus, the mutually-beneficial interplay between pathogens and tumors, named "pathogen-tumor symbionts", is probably a potential therapeutic site for tumor treatment. Herein, we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens, F. nucleatum, to break the symbiont and synergize to kill colorectal cancer (CRC) cells. This strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme (BSA-Cu SAN) which was inspired by the structures of native enzymes that are based on protein, with metal elements as the active center. BSA-Cu SAN can exert catalytic therapy by generating reactive oxygen species (ROS) and depleting GSH. The in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges F. nucleatum in situ to destroy pathogen-tumor symbionts. As a result, ROS resistance of CRC through elevated autophagy mediated by F. nucleatum was relieved, contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu SAN. Particularly, BSA-Cu SAN experiences renal clearance, avoiding long-term systemic toxicity. This work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.


Asunto(s)
Neoplasias Colorrectales , Cobre , Humanos , Especies Reactivas de Oxígeno , Cobre/farmacología , Cobre/química , Biomimética , Bacterias , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Microambiente Tumoral
3.
Front Chem ; 11: 1089775, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37065822

RESUMEN

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.

4.
Opt Lett ; 38(4): 465-7, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23455104

RESUMEN

We identify the Brillouin scattering spectrum in both the core and the cladding of an all-solid photonic bandgap fiber for the first time to our knowledge. A multipeak Brillouin spectrum with several frequency shifts and particular linewidths is investigated and related to the structural properties accordingly. Because of the different frequency dependences on the surroundings in the core and the cladding, the proposed structure exhibits potential for use as simultaneous temperature and strain sensors.

5.
Opt Lett ; 36(18): 3593-5, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21931401

RESUMEN

We demonstrate an ultrasensitive refractive-index (RI) sensor utilizing the polarimetric interference of a rectangular silica microfiber. The measured sensitivity is as high as 18,987 nm/RIU (refractive-index unit) around the RI of 1.33, which is 1 order of magnitude higher than that of the previously reported microfiber devices. Theoretical analysis reveals that such high sensitivity not only is originated from the RI-induced birefringence variation but also relies on the unique birefringence dispersion property for the rectangular microfiber. We predict that the sensitivity can be enhanced significantly when the group birefringence approaches zero.


Asunto(s)
Fibras Ópticas , Fenómenos Ópticos , Dióxido de Silicio , Birrefringencia , Dióxido de Silicio/química
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