title: Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance.
abstract: Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm(2)), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.|CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Mu
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Tan
authors.affiliation: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University , Guangzhou 510275, P. R. China.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008027:Light; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000008:administration & dosage* / Q000494:pharmacology*; D011355:Prodrugs / Q000008:administration & dosage; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D011355:Prodrugs; C062985:phytochlorin; D012822:Silicon Dioxide; D002945:Cisplatin
keywords: cisplatin; combination therapy; drug resistance; mesoporous silica nanoparticles; photodynamic therapy