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1.
Cancer Lett ; 522: 238-254, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571084

RESUMO

The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis.


Assuntos
Antígeno B7-H1/imunologia , Lipossomos/farmacologia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , Acetamidas/química , Acetamidas/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Tolerância Imunológica/efeitos dos fármacos , Imunoterapia/métodos , Indóis/química , Indóis/farmacologia , Lipossomos/química , Terapia com Luz de Baixa Intensidade , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos da radiação , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/radioterapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Piridinas/química , Piridinas/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/efeitos da radiação , Microambiente Tumoral/efeitos dos fármacos
2.
Zhongguo Zhong Yao Za Zhi ; 38(2): 167-70, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23672035

RESUMO

OBJECTIVE: To establish a HPLC-DAD method for the determination of axifolin, naringenin, quercetin and kaempferol in Cudrania tricuspidata and C. cochinchinensis in order to provide a scientific reference for species identification and quality evaluation, by establishing. METHOD: The determination was performed by HPLC-DAD on an Agilent C18 column (4.6 mm x 150 mm, 5 microm) by gradient elution (0-15 min, 35%-50% A; 15-30 min, 50% - 65% A) using methanol (A) and 0.1% phosphoric acid (B) as the mobile phase. The flow rate was 1 mL x min(-1). The detection wavelength was 290 nm for taxifolin and naringenin, 365 nm for quercetin and kaempferol with column temperature at 30 degrees C. RESULT: The content of axifolin and quercetin in the root of C. tricuspidata were remarkably higher than that in the root of C. cochinchinensis, and the content in stem of C. tricuspidata was also higher than that in the stem of C. cochinchinensis, the content of axifolin and quercetin was variable in different species. The content of naringenin and kaempferol in the root of C. cochinchinensis was visibly higher than that in the root of C. tricuspidata, and the content in the stems of the two herbs was similar, the content of naringenin and kaempferol was visibly variable in different medicinal parts of the herb, but similar between the two herbs. CONCLUSION: There's some difference of the content of the four ingredients in different medicinal parts and different herbs, so clinical use should not be confused.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonas/isolamento & purificação , Moraceae/química , Medicamentos de Ervas Chinesas/química , Flavanonas/química , Flavanonas/isolamento & purificação , Flavonas/química , Quempferóis/química , Quempferóis/isolamento & purificação , Metanol , Especificidade de Órgãos , Ácidos Fosfóricos , Raízes de Plantas/química , Caules de Planta/química , Plantas Medicinais , Quercetina/análogos & derivados , Quercetina/química , Quercetina/isolamento & purificação , Reprodutibilidade dos Testes , Especificidade da Espécie
3.
Zhongguo Zhong Yao Za Zhi ; 38(17): 2779-81, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24380297

RESUMO

OBJECTIVE: To find out the correlation between the content of taxifolin in Polygonum orientale and the storage time. METHOD: HPLC was used to determine taxifolin. The chromatographic condition was as following: Diamonsil C18 column (4.6 mm x 200 mm, 5 microm), mobile phase acetonitrile -0.1% phosphoric acid (gradient elution), the detection wavelength 290 nm and flow rate 1.0 mL x min(-1), the column temperature 30 degrees C. RESULT: The injection volume of taxifolin was in good linearity within 0.07 and 0.35 microg, the average recovery was 99.7% with RSD 0.2%. Taxifolin content was 0.84, 1.36, 1.75, 1.99 mg x g(-1) corresponding to storage time of 10, 7, 6, 5 years, respectively. CONCLUSION: The content of taxifolin decreased with the storage time. When the storage period is more than six years, the content is lower than that required by Chinese Pharmacopoeia (2010 version). This method has a good repeatability and accuracy, it provides a scientific reference for clinical use and quality evaluation of P. orientale.


Assuntos
Armazenamento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/análise , Polygonum/química , Quercetina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Quercetina/análise
4.
Toxicol In Vitro ; 27(2): 714-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23220290

RESUMO

This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model. Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400. The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol. The particle size of mixed micelles was all smaller than 100 nm. The mixed micelles with lower than 0.2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4mM and the lecithin/SDC ratio was lower than 2:1, the mixed micelles caused significant changes in cell viability and proliferation. Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner. Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0.2 and 0.6mM. The mixed micelles with more lecithin also induced less apoptosis. These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts.


Assuntos
Ácido Desoxicólico/toxicidade , Lecitinas/toxicidade , Micelas , Apoptose , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Desoxicólico/administração & dosagem , Humanos , Lecitinas/administração & dosagem
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