title: Multifunctional enveloped mesoporous silica nanoparticles for subcellular co-delivery of drug and therapeutic peptide.
abstract: A multifunctional enveloped nanodevice based on mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Mesoporous silica MCM-41 nanoparticles were used as the core for loading antineoplastic drug topotecan (TPT). The surface of nanoparticles was decorated with mitochondria-targeted therapeutic agent (Tpep) containing triphenylphosphonium (TPP) and antibiotic peptide (KLAKLAK)2 via disulfide linkage, followed by coating with a charge reversal polyanion poly(ethylene glycol)-blocked-2,3-dimethylmaleic anhydride-modified poly(L-lysine) (PEG-PLL(DMA)) via electrostatic interaction. It was found that the outer shielding layer could be removed at acidic tumor microenvironment due to the degradation of DMA blocks and the cellular uptake was significantly enhanced by the formation of cationic nanoparticles. After endocytosis, due to the cleavage of disulfide bonds in the presence of intracellular glutathione (GSH), pharmacological agents (Tpep and TPT) could be released from the nanoparticles and subsequently induce specific damage of tumor cell mitochondria and nucleus respectively with remarkable synergistic antitumor effect.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Wei-Hai
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education &Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D019772:Topotecan / Q000737:chemistry / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D009943:Organophosphorus Compounds; D010455:Peptides; C521096:triphenylphosphonium methylide; D012822:Silicon Dioxide; D019772:Topotecan