title: Gossypol-Capped Mitoxantrone-Loaded Mesoporous SiO2 NPs for the Cooperative Controlled Release of Two Anti-Cancer Drugs.
abstract: Mesoporous SiO2 nanoparticles, MP-SiO2 NPs, are functionalized with the boronic acid ligand units. The pores of the MP-SiO2 NPs are loaded with the anticancer drug mitoxantrone, and the pores are capped with the anticancer drug gossypol. The resulting two-drug-functionalized MP-SiO2 NPs provide a potential stimuli-responsive anticancer drug carrier for cooperative chemotherapeutic treatment. In vitro experiments reveal that the MP-SiO2 NPs are unlocked under environmental conditions present in cancer cells, e.g., acidic pH and lactic acid overexpressed in cancer cells. The effective unlocking of the capping units under these conditions is attributed to the acidic hydrolysis of the boronate ester capping units and to the cooperative separation of the boronate ester bridges by the lactate ligand. The gossypol-capped mitoxantrone-loaded MP-SiO2 NPs reveals preferential cytotoxicity toward cancer cells and cooperative chemotherapeutic activities toward the cancer cells. The MCF-10A epithelial breast cells and the malignant MDA-MB-231 breast cancer cells treated with the gossypol-capped mitoxantrone-loaded MP-SiO2 NPs revealed after a time-interval of 5 days a cell death of ca. 8% and 60%, respectively. Also, the gossypol-capped mitoxantrone-loaded MP-SiO2 NPs revealed superior cancer-cell death (ca. 60%) as compared to control carriers consisting of β-cyclodextrin-capped mitoxantrone-loaded (ca. 40%) under similar loading of the mitoxantrone drug. The drugs-loaded MP-SiO2 NPs reveal impressive long-term stabilities.
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Heleg-Shabtai
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Aizen
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Etery
authors.initials: E
authors.lastname: Sharon
authors.affiliation: Department of Plant and Environmental Sciences, The Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Yang Sung
authors.initials: YS
authors.lastname: Sohn
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Trifonov
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Enkin
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Lina
authors.initials: L
authors.lastname: Freage
authors.affiliation: Department of Plant and Environmental Sciences, The Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Nechushtai
authors.affiliation: Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Willner
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006072:Gossypol / Q000737:chemistry*; D006801:Humans; D008942:Mitoxantrone / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012822:Silicon Dioxide; D008942:Mitoxantrone; D006072:Gossypol
keywords: boronate ester; boronic acid; breast cancer; drug release; pH-responsive