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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

Physicochemical characterization of PLD/CDDP nanoparticles.(a) Size distribution analysis of PLD/CDDP evaluated using zetasizer, (b) TEM images of PLD/CDDP, (c) X-Ray diffraction analysis of free CDDP and PLD/CDDP. (d) In vitro release profile of CDDP from PLD/CDDP nanoparticles. The study was performed in phosphate buffered saline (pH 7.4) at 37 °C. Data are expressed as standard deviation of the mean and n = 3. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.
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f2: Physicochemical characterization of PLD/CDDP nanoparticles.(a) Size distribution analysis of PLD/CDDP evaluated using zetasizer, (b) TEM images of PLD/CDDP, (c) X-Ray diffraction analysis of free CDDP and PLD/CDDP. (d) In vitro release profile of CDDP from PLD/CDDP nanoparticles. The study was performed in phosphate buffered saline (pH 7.4) at 37 °C. Data are expressed as standard deviation of the mean and n = 3. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.

Mentions: The particle size of PLD/CDDP was studied using dynamic light scattering technique (DLS). DLS analysis showed an average size of ~180 nm with a narrow polydispersity index (PDI~0.24) (Fig. 2a). The mean size of nanoparticle was below <200 nm which is in the range of tumor vasculature permeation, suggesting that PLD/CDDP cold effectively accumulate in the solid tumours via enhanced permeation and retention (EPR) effect22. Such characteristics of nanosystem could potentially increase the chemotherapeutic efficacy of anticancer drugs. The drug loading capacity of CDDP was studied spectrophotometrically. The PLD micelles showed a high entrapment efficiency of >90% with a high loading capacity of 28.5% w/w.


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)

Physicochemical characterization of PLD/CDDP nanoparticles.(a) Size distribution analysis of PLD/CDDP evaluated using zetasizer, (b) TEM images of PLD/CDDP, (c) X-Ray diffraction analysis of free CDDP and PLD/CDDP. (d) In vitro release profile of CDDP from PLD/CDDP nanoparticles. The study was performed in phosphate buffered saline (pH 7.4) at 37 °C. Data are expressed as standard deviation of the mean and n = 3. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume 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

f2: Physicochemical characterization of PLD/CDDP nanoparticles.(a) Size distribution analysis of PLD/CDDP evaluated using zetasizer, (b) TEM images of PLD/CDDP, (c) X-Ray diffraction analysis of free CDDP and PLD/CDDP. (d) In vitro release profile of CDDP from PLD/CDDP nanoparticles. The study was performed in phosphate buffered saline (pH 7.4) at 37 °C. Data are expressed as standard deviation of the mean and n = 3. *p < 0.05 and **p < 0.01 is the statistical difference between tumor volume of CDDP and CDDP/PLD treated group.
Mentions: The particle size of PLD/CDDP was studied using dynamic light scattering technique (DLS). DLS analysis showed an average size of ~180 nm with a narrow polydispersity index (PDI~0.24) (Fig. 2a). The mean size of nanoparticle was below <200 nm which is in the range of tumor vasculature permeation, suggesting that PLD/CDDP cold effectively accumulate in the solid tumours via enhanced permeation and retention (EPR) effect22. Such characteristics of nanosystem could potentially increase the chemotherapeutic efficacy of anticancer drugs. The drug loading capacity of CDDP was studied spectrophotometrically. The PLD micelles showed a high entrapment efficiency of >90% with a high loading capacity of 28.5% w/w.

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