Co-delivery of Doxorubicin and Afatinib with pH-responsive Polymeric Nanovesicle for Enhanced Lung Cancer Therapy

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.

Co-delivery of Andrographolide and Notch1-targeted siRNA to Macrophages with Polymer-based Nanocarrier for Enhanced Anti-inflammation

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.