Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feas...Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.展开更多
Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspar...Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspartic acid) grafted with diethylenetriamine, lysine and cholic acid (PEG-PAsp(DETA)-Lys-CA2) polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide (LPS)-activated interleukin-6 (IL-6) and monocytes chemotactic protein 1 (MCP-1) expression as well as blocked nuclear factor-rd3 (NF-rd3) signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 (IL-10) and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.展开更多
基金financially supported by the National Basic Research Program of China (No. 2015CB755500)the Natural Science Foundation of Guangdong Province (No. 2014A030312018)Science and Technology Planning Project of Guangdong Province (No. 2016A020215088)
文摘Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.
基金financially supported by the National Natural Science Foundation of China (No. U1401242)National Basic Research Program of China (No. 2015CB755500)+1 种基金the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2013S086)the Fundamental Research Funds for the Central Universities (Nos. 17lgjc01 and 17lgpy08)
文摘Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspartic acid) grafted with diethylenetriamine, lysine and cholic acid (PEG-PAsp(DETA)-Lys-CA2) polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notchl gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notchl siRNA not only significantly inhibited lipopolysaccharide (LPS)-activated interleukin-6 (IL-6) and monocytes chemotactic protein 1 (MCP-1) expression as well as blocked nuclear factor-rd3 (NF-rd3) signal activation, but also interfered the Notchl gene expression and increased anti-inflammatory cytokines such as interleukin-10 (IL-10) and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notchl siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of proinflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.