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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

Immunohistochemistry studies performed in tumor samples.The expression level of CD31 and Ki67 apoptosis markers were investigated in extracted tumor samples.
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f7: Immunohistochemistry studies performed in tumor samples.The expression level of CD31 and Ki67 apoptosis markers were investigated in extracted tumor samples.

Mentions: To determine the biological effects of free CDDP and PLD/CDDP, tumors were extracted from the sacrificed mice, fixed with 10% formalin, and subjected to vessel marker (CD31) and cellular proliferation (Ki67) assays. CD31 is a transmembrane glycoprotein and a platelet endothelial cell adhesion molecule that recognizes newly formed vasculature. Ki67 is involved in regulation of cell cycle and highly expressed in proliferating cells and is regarded as a one of the most prominent markers of cell proliferation or cell apoptosis. As shown in Fig. 7, marked reduction in the number of CD31 stained tumor blood vessels were observed in PLD/CDDP treated mice group. Similarly, Ki67 staining intensity was remarkably decreased in the formulation treated group. Therefore, decrease in the expression of CD31 and Ki67 is a clear indication of the superior therapeutic efficacy of PLD/CDDP nanoformulations.


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)

Immunohistochemistry studies performed in tumor samples.The expression level of CD31 and Ki67 apoptosis markers were investigated in extracted tumor samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Immunohistochemistry studies performed in tumor samples.The expression level of CD31 and Ki67 apoptosis markers were investigated in extracted tumor samples.
Mentions: To determine the biological effects of free CDDP and PLD/CDDP, tumors were extracted from the sacrificed mice, fixed with 10% formalin, and subjected to vessel marker (CD31) and cellular proliferation (Ki67) assays. CD31 is a transmembrane glycoprotein and a platelet endothelial cell adhesion molecule that recognizes newly formed vasculature. Ki67 is involved in regulation of cell cycle and highly expressed in proliferating cells and is regarded as a one of the most prominent markers of cell proliferation or cell apoptosis. As shown in Fig. 7, marked reduction in the number of CD31 stained tumor blood vessels were observed in PLD/CDDP treated mice group. Similarly, Ki67 staining intensity was remarkably decreased in the formulation treated group. Therefore, decrease in the expression of CD31 and Ki67 is a clear indication of the superior therapeutic efficacy of PLD/CDDP nanoformulations.

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