RESUMO
Cell culturing on different synthetic biomaterials would reprogram cell metabolism for adaption to their living conditions because such alterations in cell metabolism were necessary for cellular functions on them. Here we used metabolomics to uncover metabolic changes when liver cells were cultured on insulin-like growth factor (IGF)/tumor necrosis factor-α (TNF-α) and chargeable polymers co-modified biomaterials with the aim to explain their modulating effects on cell metabolism. The results showed that cell metabolism on IGF-1/TNF-α co-immobilized conjugates was significantly regulated according to their scatterings on the score plot of principal component analysis. Specifically, cell metabolisms were reprogrammed to the higher level of pyrimidine metabolism, ß-alanine metabolism, and pantothenate and CoA biosynthesis, and the lower level of methionine salvage pathway in order to promote cell growth on IGF/TNF-α co-modified surface. Furthermore, cell senescence on PSt-PAAm-IGF/TNF-α surface was delayed through the regulation of branch amino acid metabolism and AMPK signal pathway. The research showed that metabolomics had great potential to uncover the molecular interaction between biomaterials and seeded cells, and provide the insights about cell metabolic reprogramming on IGF/TNF-α co-modified conjugates for cell growth.
Assuntos
Proliferação de Células , Fator de Crescimento Insulin-Like I , Polímeros , Transdução de Sinais , Fator de Necrose Tumoral alfa , Células Hep G2 , Humanos , Fator de Crescimento Insulin-Like I/química , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Polímeros/química , Polímeros/farmacologia , Fator de Necrose Tumoral alfa/química , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer.
Assuntos
Antineoplásicos/administração & dosagem , Bacillus coagulans , Neoplasias do Colo/tratamento farmacológico , Curcumina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácido Fólico/administração & dosagem , Esporos Bacterianos , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Ácido Fólico/química , Ácido Fólico/farmacocinética , Células HT29 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos Sprague-DawleyRESUMO
Photodynamic therapy (PDT), combining the laser and photosensitizers to kill tumor cells, has the potential to address many current medical requirements. In this study, magnetic Fe3O4 nanoparticles were first employed as cores and modified with oleic acid (OA) and 3-triethoxysilyl-1-propanamine. Then, the photosensitizers phycocyanin (PC) and hematoporphyrin monomethyl ether (HMME), which might be able to stimulate the cell release of reactive oxygen species after the irradiation of a near-infrared (NIR) laser, were grafted on the surface of such nanoparticles. Our results revealed the high-efficiency inhibition of breast cancer MCF-7 cells growing upon near-infrared irradiation both in vitro and in vivo. Furthermore, it was the synergy between the natural photosensitizers PC and the synthetic photosensitizers HMME that deeply influenced such inhibition compared to the groups that used either of these medicines alone. To utilize the combination of different photosensitive agents, our study thus provides a new strategy for breast cancer treatment.