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Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.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%).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic synthesis of poly (lactic-co-glycolic acid) (PLGA)-dextran sulphate (DS) block copolymer.The CDDP and PLGA-DS self-assembled to forms a polymeric nanoparticles in which PLGA forms the core and DS forms the outer surface.
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f1: Schematic synthesis of poly (lactic-co-glycolic acid) (PLGA)-dextran sulphate (DS) block copolymer.The CDDP and PLGA-DS self-assembled to forms a polymeric nanoparticles in which PLGA forms the core and DS forms the outer surface.

Mentions: The PLGA-DX polymer block was fabricated by the reaction between amine terminated-PLGA block and activated DS polymer block. The PLGA-DX was loaded with CDDP using a self-assembling process where in the drug was loaded in the core of the polymeric micelles (Fig. 1). The critical micelle concentration (CMC) of the Dex-PLGA was measured using pyrene as a hydrophobic fluorescent probe. the I1 and I3 of pyrene increased simultaneously while the I3 of pyrene increased significantly than that of I1, which led to the decreased of I1/I3 ratio quickly as the concentration of PLGA-DS polymer increased. The CMC of PLD was observed to be ~50 μg/mL (data not shown); indicating its excellent thermodynamic stability in the solution. Lower CMC value of a polymer is a indication of its ability to self-assemble in the aqueous medium.


Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

Liu P, Sun L, Zhou DS, Zhang P, Wang YH, Li D, Li QH, Feng RJ - Sci Rep (2015)

Schematic synthesis of poly (lactic-co-glycolic acid) (PLGA)-dextran sulphate (DS) block copolymer.The CDDP and PLGA-DS self-assembled to forms a polymeric nanoparticles in which PLGA forms the core and DS forms the outer surface.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664968&req=5

f1: Schematic synthesis of poly (lactic-co-glycolic acid) (PLGA)-dextran sulphate (DS) block copolymer.The CDDP and PLGA-DS self-assembled to forms a polymeric nanoparticles in which PLGA forms the core and DS forms the outer surface.
Mentions: The PLGA-DX polymer block was fabricated by the reaction between amine terminated-PLGA block and activated DS polymer block. The PLGA-DX was loaded with CDDP using a self-assembling process where in the drug was loaded in the core of the polymeric micelles (Fig. 1). The critical micelle concentration (CMC) of the Dex-PLGA was measured using pyrene as a hydrophobic fluorescent probe. the I1 and I3 of pyrene increased simultaneously while the I3 of pyrene increased significantly than that of I1, which led to the decreased of I1/I3 ratio quickly as the concentration of PLGA-DS polymer increased. The CMC of PLD was observed to be ~50 μg/mL (data not shown); indicating its excellent thermodynamic stability in the solution. Lower CMC value of a polymer is a indication of its ability to self-assemble in the aqueous medium.

Bottom Line: PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP.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%).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.

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.

No MeSH data available.


Related in: MedlinePlus