title: Cytochrome c end-capped mesoporous silica nanoparticles as redox-responsive drug delivery vehicles for liver tumor-targeted triplex therapy in vitro and in vivo.
abstract: To develop carriers for efficient anti-cancer drug delivery with reduced side effects, a biocompatible and redox-responsive nanocontainer based on mesoporous silica nanoparticles (MSNs) for tumor-targeted triplex therapy was reported in this study. The nanocontainer was fabricated by immobilizing cytochrome c (CytC) onto the MSNs as sealing agent via intermediate linkers of disulfide bonds for redox-responsive intracellular drug delivery. AS1411 aptamer was further tailored onto MSNs for cell/tumor targeting. The successful construction of redox- responsive MSNs was confirmed by BET/BJH analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermogravimetric analysis (TGA), respectively. Detailed investigations demonstrated that anticancer drug of doxorubicin (DOX) loaded nanocontainer could be triggered by reductant (e.g. glutathione) within cellular microenvironment and release DOX to induce tumor cell apoptosis in vitro. More importantly, the nanocontainer displayed great potential for tumor targeting and achieved triplex therapy effects on the tumor inhibition in vivo through the loading DOX, gatekeeper of CytC and AS1411 aptamer, which were reflected by the change of tumor size, TUNEL staining and HE staining assays.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Beilu
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Ding
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China. Electronic address: kaiyong_cai@cqu.edu.cn.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000627:therapeutic use; D045304:Cytochromes c / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D003692:Delayed-Action Preparations; D012822:Silicon Dioxide; D004317:Doxorubicin; D045304:Cytochromes c
keywords: Cytochrome c; In vivo; Mesoporous silica nanoparticles; Redox-responsive delivery; Tumor-targeted therapy