title: Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging.
abstract: Functional nanocarriers capable of transporting high drug contents without premature leakage and to controllably deliver several drugs are needed for better cancer treatments. To address this clinical need, gold cluster bovine serum albumin (AuNC@BSA) nanogates were engineered on mesoporous silica nanoparticles (MSN) for high drug loadings and co-delivery of two different anticancer drugs. The first drug, gemcitabine (GEM, 40wt%), was loaded in positively-charged ammonium-functionalized MSN (MSN-NH3(+)). The second drug, doxorubicin (DOX, 32wt%), was bound with negatively-charged AuNC@BSA electrostatically-attached onto MSN-NH3(+), affording highly loaded pH-responsive MSN-AuNC@BSA nanocarriers. The co-delivery of DOX and GEM was achieved for the first time via an inorganic nanocarrier, possessing a zero-premature leakage behavior as well as drug loading capacities seven times higher than polymersome NPs. Besides, unlike the majority of strategies used to cap the pores of MSN, AuNC@BSA nanogates are biotools and were applied for targeted red nuclear staining and in-vivo tumor imaging. The straightforward non-covalent combination of MSN and gold-protein cluster bioconjugates thus leads to a simple, yet multifunctional nanotheranostic for the next generation of cancer treatments.
authors.affiliation: Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia; Department of Chemistry and Biochemistry, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Jonas G
authors.initials: JG
authors.lastname: Croissant
authors.affiliation: Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Dingyuan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Shahad
authors.initials: S
authors.lastname: Alsaiari
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Tamanoi
authors.affiliation: Life science and Environment Research Institute, Center of Excellence in Nanomedicine, King Abdulaziz City for Science and Technology (KACST), Riyadh Kingdom of Saudi Arabia.
authors.forename: Abdulaziz M
authors.initials: AM
authors.lastname: AlMalik
authors.affiliation: Department of Chemistry and Biochemistry, California NanoSystems Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Zink
authors.affiliation: Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia. Electronic address: niveen.khashab@kaust.edu.sa.
authors.forename: Niveen M
authors.initials: NM
authors.lastname: Khashab
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D003841:Deoxycytidine; D012710:Serum Albumin, Bovine; D006046:Gold; D012822:Silicon Dioxide; D004317:Doxorubicin; D000093542:Gemcitabine
keywords: Bovine serum albumin; Cancer; Gold nanoclusters; Mesoporous silica nanoparticles; Multi-drug delivery