title: Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.
abstract: In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.
authors.affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Yong-hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Qing-hu
authors.initials: QH
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
authors.forename: Rong-Jie
authors.initials: RJ
authors.lastname: Feng
mesh_terms: D019386:Alendronate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D023041:Xenograft Model Antitumor Assays
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002945:Cisplatin; D019386:Alendronate