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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

Annexin V/PI based apoptosis analysis in MG63 cancer cells.The cells were treated with free CDDP and PLD/CDDP and incubated for 24 and 48 h, respectively. The respective cell percentages in early and late apoptosis for different time period 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 apoptosis potential of CDDP and CDDP/PLD treated group.
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f4: Annexin V/PI based apoptosis analysis in MG63 cancer cells.The cells were treated with free CDDP and PLD/CDDP and incubated for 24 and 48 h, respectively. The respective cell percentages in early and late apoptosis for different time period 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 apoptosis potential of CDDP and CDDP/PLD treated group.

Mentions: To elucidate the mechanism of cell death and to confirm the potential of nanoparticles in inducing apoptosis, cells were stained with Annexin V and propidium iodide (PI). Annexin V binds to the phosphatidylserine which are generally present in the outer cell surface of apoptotic cells. PI stains the nucleus of late apoptotic and necrotic cells. As seen from Fig. 4, significant proportion of cells (p < 0.01) was present in the early and late apoptotic chambers after treatment with either free CDDP or PLD/CDDP. Moreover, time-dependent apoptosis of cancer cells were observed after the treatment. Consistent with the cytotoxicity assay, PLD/CDDP exhibited a significant apoptosis of MG63 cells compared to that of free CDDP. For example, ~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. Therefore it is clear that nanoparticulate formulation of CDDP remarkably increased the therapeutic performance of anticancer drug.


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)

Annexin V/PI based apoptosis analysis in MG63 cancer cells.The cells were treated with free CDDP and PLD/CDDP and incubated for 24 and 48 h, respectively. The respective cell percentages in early and late apoptosis for different time period 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 apoptosis potential 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

f4: Annexin V/PI based apoptosis analysis in MG63 cancer cells.The cells were treated with free CDDP and PLD/CDDP and incubated for 24 and 48 h, respectively. The respective cell percentages in early and late apoptosis for different time period 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 apoptosis potential of CDDP and CDDP/PLD treated group.
Mentions: To elucidate the mechanism of cell death and to confirm the potential of nanoparticles in inducing apoptosis, cells were stained with Annexin V and propidium iodide (PI). Annexin V binds to the phosphatidylserine which are generally present in the outer cell surface of apoptotic cells. PI stains the nucleus of late apoptotic and necrotic cells. As seen from Fig. 4, significant proportion of cells (p < 0.01) was present in the early and late apoptotic chambers after treatment with either free CDDP or PLD/CDDP. Moreover, time-dependent apoptosis of cancer cells were observed after the treatment. Consistent with the cytotoxicity assay, PLD/CDDP exhibited a significant apoptosis of MG63 cells compared to that of free CDDP. For example, ~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. Therefore it is clear that nanoparticulate formulation of CDDP remarkably increased the therapeutic performance of anticancer drug.

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