title: Mesoporous silica nanoparticles for the improved anticancer efficacy of cis-platin.
abstract: We designed a novel cis-platin (CP) delivery system by modification of mesoporous silica nanoparticle (MSN) surfaces with a carboxylate group through a hydrazone bond. The further immobilization of CP can be achieved through the coordination of the carboxylate-modified MSN surfaces with the hydroxo-substituted CP. This new formulation can efficiently increase efficiency of both the cellular uptake and the drug release under endosomal or lysosomal pHs; therefore, the anti-proliferative effect of this new formulation on the colon cancer cell line (HT-29) was twenty times more than the free CP molecules. In addition, the encapsulation of CP complexes in the confined spaces of MSNs can decrease non-specific release from enzymatic hydrolysis because most hydrolytic enzymes have diameters considerably greater than the pore size of MSNs. The DNA fragmentation and caspase-3 activity assay showed that the apoptosis was induced by DNA damages and then an increase in caspase-3 activity. Thus, the TA-MSN-carboxylate-CP samples were induced cell apoptosis through the caspase-3 dependent pathway. Moreover, the hemolysis assay also indicated that the exposure of the carboxylate-modified MSNs in red blood cells (RBCs) did not observe the release of red hemoglobin from the cell lysis, and the further exposure of the TA-MSN-carboxylate-CP complexes to RBCs also did not observe notably the lysis of RBCs under the effectively therapeutic dosage. Therefore, our design of MSN with controllable release of CP has highly therapeutic effects and is highly biocompatible; however, a low cytotoxicity and site effect were observed.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lin
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Cheng
authors.forename: Wei-Neng
authors.initials: WN
authors.lastname: Liao
authors.forename: Pei-Ru
authors.initials: PR
authors.lastname: Wei
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D015195:Drug Design; D006041:Goats; D019073:HT29 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D012822:Silicon Dioxide; D002945:Cisplatin