title: Targeted osteosarcoma chemotherapy using RGD peptide-installed doxorubicin-loaded biodegradable polymeric micelle.
abstract: Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)-block-poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer, for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%-73% displayed a narrow distribution (PDI=0.05-0.12) with average sizes ranging from 46 to 73nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC50) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Orthopaedics, Luoyang Orthopedic-Traumatological Hospital, No. 1 Qiming Road, Luoyang, 450000, China.
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China.
authors.forename: Wusheng
authors.initials: W
authors.lastname: Kan
authors.affiliation: Department of Orthopaedics, Wuhan Puai Hospital, 473 Hanzheng Street, Wuhan, 430000, China. Electronic address: strongspine@163.com.
authors.forename: Runsheng
authors.initials: R
authors.lastname: Miao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004146:Dioxanes / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008823:Micelles; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004146:Dioxanes; D008823:Micelles; D009842:Oligopeptides; D011108:Polymers; C059299:polytrimethylene carbonate; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin
keywords: Nanoparticulate drug delivery system; Osteosarcoma; RGD; Targeted chemotherapy