title: Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation.
abstract: Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.
authors.affiliation: Department of Orthopedic Surgery, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China.
authors.forename: Zi-Fei
authors.initials: ZF
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China.
authors.forename: Tuan-Wei
authors.initials: TW
authors.lastname: Sun
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address: fchen@mail.sic.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Zuo
authors.affiliation: Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China.
authors.forename: Ying-Qi
authors.initials: YQ
authors.lastname: Hua
authors.affiliation: Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, PR China. Electronic address: czd856@vip.sohu.com.
authors.forename: Zheng-Dong
authors.initials: ZD
authors.lastname: Cai
authors.affiliation: Department of Orthopedic Surgery, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China. Electronic address: dr.tan@139.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D020341:Absorbable Implants; D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002130:Calcium Phosphates / Q000008:administration & dosage*; D002214:Capsules / Q000008:administration & dosage / Q000138:chemical synthesis*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D016062:Porosity; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D002214:Capsules; D004317:Doxorubicin; C020243:calcium phosphate; D000241:Adenosine
keywords: Bioactivity; Calcium phosphate; Drug delivery; Osteogenic differentiation; Osteosarcoma