As the major redox couple and nonprotein thiol source in human tissues, the level of glutathione (GSH) has been a concern for its relation with many diseases. However, the similar physical and chemical properties of interference molecules such as cysteine (Cys) and homocysteine (Hcy) make discriminative detection of GSH in complex biological fluids challenging. Here we report a novel surface-enhanced Raman scattering (SERS) platform, based on silver-nanoparticleembedded porous silicon disks (PSDs/Ag) substrates for highly sensitive and selective detection of GSH in biofluids. Silver nanoparticles (AgNPs) were reductively synthesized and aggregated directly into pores of PSDs, achieving a SERS enhancement factor (EF) up to 2.59 × 10 7 . Ellman's reagent 5,5′-ditho-bis (2-nitrobenzoic acid) (DTNB) was selected as the Raman reactive reporting agent, and the GSH quantification was determined using enzymatic recycling method, and allowed the detection limit of GSH to be down to 74.9 nM using a portable Raman spectrometer. Moreover, the significantly overwhelmed enhancement ratio of GSH over other substances enables the discrimination of GSH detection in complex biofluids.
Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis. We systematically characterized this platform (CP-MSNP@DOX/PKM2) in vitro and evaluated its therapeutic efficacy in vivo with a mouse model of triple negative breast cancer (TNBC). Exposure of TNBC cells to CP-MSNP@DOX/PKM2 resulted in suppressed target gene expression, reduced cell proliferation, and enhanced apoptosis. Intravenous administration of the drug substantially decreased the tumor burden in comparison to DOX or siRNA monotherapy. In conclusion, we have developed a platform for efficient co-delivery of small molecule drugs and therapeutic siRNA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.