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The dense extracellular matrix (ECM) in the pancreatic cancer severely hampers the penetration of nanodrugs, which causes inferior therapeutic efficacy. To address this issue, a multifunctional liposome, namely, Lip-DTI/NO, integrating a type-I photosensitizer DTITBT with glutathione (GSH) or heat-responsive nitric oxide (NO) donor S-nitroso-N-acetyl-D-penicillamine (SNAP) is constructed to deplete the tumor ECM, leading to enhanced drug delivery and consequently improved phototherapy. The loaded DTITBT possesses multiple functions including NIR-II fluorescence imaging, efficient superoxide radical (O2 â¢-) generation and excellent photothermal conversion efficiency, making it feasible for precisely pinpointing the tumor in the phototherapy process. Responding to the intracellular overexpressed glutathione or heat produced by photothermal effect of DTITBT, NO can be released from SNAP. Upon 808 nm laser irradiation, Lip-DTI/NO could selectively induce in situ generation of peroxynitrite anion (ONOO-) in tumor after cascade processes including O2 â¢- production, GSH or heat-triggered NO release, and rapid reaction between O2 â¢- and NO. The generated ONOO- could activate the expression of endogenous matrix metalloproteinases which could efficiently digest collagen of tumor ECM, thus facilitating enhanced penetration and accumulation of Lip-DTI/NO in tumor. In vivo evaluation demonstrates the notable therapeutic efficacy via ONOO--potentiated synergistic photodynamic-photothermal therapies on both subcutaneous and orthotopic pancreatic cancer model.
Asunto(s)
Nanopartículas , Neoplasias , Neoplasias Pancreáticas , Fotoquimioterapia , Humanos , Óxido Nítrico , Fototerapia/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Colágeno , Glutatión , Línea Celular TumoralRESUMEN
Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Liposomas/uso terapéutico , Terapia Fototérmica , Especies Reactivas de Oxígeno , Neoplasias Hepáticas/tratamiento farmacológico , Fototerapia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Traditional Chinese medicine (TCM) and western medicine have their respective advantages and limitations in the diagnosis and treatment of common otorhinolaryngology head and neck diseases. Although the integrated TCM and western medicine exhibits definite curative effects, there is no consensus on the otorhinolaryngology head and neck diseases responding specifically to TCM or integrated TCM and western medicine, as well as the diagnosis and treatment schemes. The China Association of Chinese Medicine (CACM) thus organized the otorhinolaryngology head and neck specialists of both TCM and western medicine to discuss the etiology, pathogenesis, and clinical diagnosis and treatment methods of common otorhinolaryngology head and neck diseases with the results of multiple clinical trials taken into account. The acute pharyngitis, chronic pharyngolaryngitis, paraesthesia pharyngis, hysterical aphasia, allergic rhinitis, subjective tinnitus, and otogenic vertigo were confirmed to respond specifically to TCM or integrated TCM and western medicine. Then a mutually agreed diagnosis and treatment scheme and recommendation with integrated TCM and western medicine was formulated as a reference for clinical practice, thus benefiting more patients.
RESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of Ganoderma lucidum polysaccharides (GLPs) on advanced glycation end products (AGEs) and the receptor (RAGE) of aorta pectoralis in the T2DM rats, and explore the protective mechanism of GLPs on the aorta pectoralis.</p><p><b>METHOD</b>SD rats were fed with high-fat diet for 4 weeks and then were injected STZ (30 mg x kg(-1)) to induce the type 2 diabetic rats. Once the T2DM models were set successfully, rats were randomly divided into normal control group, diabetes model (DM) group, berberine (30 mg x kg(-1)) group, GLPs of low (GLPs-L), middle (GLPs-M) and high-dose (GLPs-H) group (GLPs were orally given 200, 400, 800 mg x kg(-1)). After 12 weeks' treatment, the content of fasting blood glucose and AGEs in serum were detected. The expressions of AGEs and RAGE in aortas pectoralis were measured both by immunohistochemistric assays and western-blot analysis.</p><p><b>RESULT</b>Compared with DM group, the content of blood glucose and AGEs in serum were significantly decreased in GLPs-H group and GLPs-M group (P < 0.01). Compared with DM group, the expressions of AGEs and RAGE in aorta pectoralis were decreased in other groups, especially in GLPs-H group (P < 0. 01).</p><p><b>CONCLUSION</b>GLPs could low blood glucose and protect aortas effectively. The mechanisms may be involved in down-regulation the expressions of AGEs and RAGE in aortal tissue.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratas , Aorta , Metabolismo , Patología , Glucemia , Diabetes Mellitus Tipo 2 , Metabolismo , Patología , Productos Finales de Glicación Avanzada , Metabolismo , Extractos Vegetales , Farmacología , Polisacáridos , Farmacología , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos , Metabolismo , Reishi , QuímicaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of Ganoderma lucidum polysaccharides (GLPs) on hemodynamic and antioxidation in the T2DM rats.</p><p><b>METHOD</b>SD rats were fed high-fat diet for 4 weeks and then were injected STZ (30 mg x kg(-1)) to induce the type 2 diabetes mellitus (T2DM). Once the T2DM models were set successfully, rats were randomized into six groups: normal group (NG), group of diabetes mellitus (DMG), groups of low dosage (GLPs-LG), middle dosage (GLPs-MG), high dosage (GLPs-HG) and berberine (BerG). They received GLPs with different dosages (200, 400, 800 mg x kg(-1)) and berberine (30 mg x kg(-1)) continually for 16 weeks. At 16th weekend, the following indices of rats were measured respectively: blood glucose, hemodynamic including LVSP, LVEDP, dp/dt(max) and -dp/dt(max) and the contents of NO, SOD, MDA, GSH-Px, CAT in cardiac tissue. Besides, myocardial ultrastructure was observed by electron microscope.</p><p><b>RESULT</b>Both the middle dosage and the high dosage of GLPs could low blood glucose effectively, and they could reduce LVEP but increase -dp/dt(max). Meanwhile, they could activate GSH-Px, CAT, SOD, NO, but reduce MDA in cardiac tissue and improve the myocardial ultrastructure. Compared to the DM group, the middle dosage, high dosage of GLPs and berberine showed significant improvement. Compared to the berberine group, the middle dosage showed the same effect, but the high dosage was more effective than berberine.</p><p><b>CONCLUSION</b>There is a confirmed action of GLPs in improving the hemodynamic and antioxidation in cardiac tissue of T2DM rats.</p>