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: Ping Liu, Liang Sun, Dong-sheng Zhou, Peng Zhang, Yong-hui Wang, Dong Li, Qing-hu Li, Rong-Jie Feng
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 17387 (Dec 01 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26619950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Dextrans
• Drug Carriers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Cisplatin
• Alendronate

Topics

• Alendronate (chemistry, pharmacokinetics, pharmacology)
• Animals
• Bone Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cisplatin (chemistry, pharmacokinetics, pharmacology)
• Dextrans (chemistry, pharmacokinetics, pharmacology)
• Drug Carriers (chemistry, pharmacokinetics, pharmacology)
• Humans
• Lactic Acid (chemistry, pharmacokinetics, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Osteosarcoma (drug therapy, metabolism, pathology)
• Polyglycolic Acid (chemistry, pharmacokinetics, pharmacology)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Xenograft Model Antitumor Assays