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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

Cell cycle analysis of MG63 cancer cells after treatment with free CDDP and PLD/CDDP for 24 h.The respective cell percentages in G2/M and G0/G1 phases are presented in the bar graph. Data are expressed as standard deviation of the mean and n = 4. **p < 0.01 is the statistical difference between G2/M phase expression of CDDP and CDDP/PLD treated group.
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f5: Cell cycle analysis of MG63 cancer cells after treatment with free CDDP and PLD/CDDP for 24 h.The respective cell percentages in G2/M and G0/G1 phases are presented in the bar graph. Data are expressed as standard deviation of the mean and n = 4. **p < 0.01 is the statistical difference between G2/M phase expression of CDDP and CDDP/PLD treated group.

Mentions: The influence of CDDP on the cell cycle progression was investigated by means of flow cytometry (Fig. 5). The results clearly showed that CDDP induced a typical G2/M phase arrest in MG63 cancer cells. Importantly, PLD/CDDP exhibited a significantly (p < 0.01) higher G2/M phase arrest in this cancer cell than comparing to free CDDP. It can be seen that nearly 2-fold higher G2/M arrest was observed in case of PLD/CDDP treated group (~60%). At the same time, cells in the G0/G1 phase decreased significantly (p < 0.01). This would result in enhanced cancer cell death. It has been reported that CDDP induce programmed cell death by inhibiting cells at G2 phase of cell cycle2728. Therefore, nanoformulations of CDDP would be much superior in acting on different phases of cancer cell cycle.


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)

Cell cycle analysis of MG63 cancer cells after treatment with free CDDP and PLD/CDDP for 24 h.The respective cell percentages in G2/M and G0/G1 phases are presented in the bar graph. Data are expressed as standard deviation of the mean and n = 4. **p < 0.01 is the statistical difference between G2/M phase expression of CDDP and CDDP/PLD treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Cell cycle analysis of MG63 cancer cells after treatment with free CDDP and PLD/CDDP for 24 h.The respective cell percentages in G2/M and G0/G1 phases are presented in the bar graph. Data are expressed as standard deviation of the mean and n = 4. **p < 0.01 is the statistical difference between G2/M phase expression of CDDP and CDDP/PLD treated group.
Mentions: The influence of CDDP on the cell cycle progression was investigated by means of flow cytometry (Fig. 5). The results clearly showed that CDDP induced a typical G2/M phase arrest in MG63 cancer cells. Importantly, PLD/CDDP exhibited a significantly (p < 0.01) higher G2/M phase arrest in this cancer cell than comparing to free CDDP. It can be seen that nearly 2-fold higher G2/M arrest was observed in case of PLD/CDDP treated group (~60%). At the same time, cells in the G0/G1 phase decreased significantly (p < 0.01). This would result in enhanced cancer cell death. It has been reported that CDDP induce programmed cell death by inhibiting cells at G2 phase of cell cycle2728. Therefore, nanoformulations of CDDP would be much superior in acting on different phases of cancer cell cycle.

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