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Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution.

Hou Z, Zhan C, Jiang Q, Hu Q, Li L, Chang D, Yang X, Wang Y, Li Y, Ye S, Xie L, Yi Y, Zhang Q - Nanoscale Res Lett (2011)

Bottom Line: Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group.In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release.Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Hospital, Xiamen University, Xiamen, 361003, China. Xly885@163.com.

ABSTRACT
Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments.

No MeSH data available.


Related in: MedlinePlus

Confocal images. Confocal images of HeLa cells after incubated 24 h with different kinds of modified NPs at the same concentration 0.1 mg/ml; the nuclei were stained by DAPI (blue), and all of the NPs are labeled by rhodamine B (red). (a) Incubated with pure NPs; (b) incubated with FA-NPs; (c) incubated with mPEG-NPs; (d) incubated with mPEG-FA-NPs.
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Figure 6: Confocal images. Confocal images of HeLa cells after incubated 24 h with different kinds of modified NPs at the same concentration 0.1 mg/ml; the nuclei were stained by DAPI (blue), and all of the NPs are labeled by rhodamine B (red). (a) Incubated with pure NPs; (b) incubated with FA-NPs; (c) incubated with mPEG-NPs; (d) incubated with mPEG-FA-NPs.

Mentions: To visualize the effect of FA-mediated endocytosis of different kinds of modified NPs, the distribution of rhodamine B-labeled NPs on HeLa cells was observed by confocal laser scanning microscopy (Figure 6). By 24-h incubation time, both FA-NPs and mPEG-FA-NPs show high intracellular rhodamine B concentration, which was visualized by red intensity of rhodamine B. Nevertheless, in case of mPEG-NPs, rhodamine B was significantly localized probably in the outside of the cells instead of a distribution in the endosomes, indicating that the mPEG-NPs tended to reduce the cell uptakes. In contrast, for blank NPs (Figure 6a), only low red intensity appeared in the peripheral region of the cells due to slow diffusion process into the cells for 24-h incubation period. NPs are generally internalized into cells via fluid phase endocytosis [26], phagocytosis [27], or receptor-mediated endocytosis [28]. Physicochemical characteristics such as particle size and surface properties played key roles in the cellular of NPs [29]. NP uptake could be considered as an adhesion process followed by an internalization process [30]. However, surface modification of NPs with PEG in our result seems to oppose uptake by the HeLa cells, which is mainly due to the formation of a dense, hydrophilic cloud of long flexible chains on the surface of the NPs that reduces the hydrophobic interactions with the membrane of tumor cells. The chemically anchored PEG chains can undergo spatial conformations, thus preventing the internalization of NPs by the cells. Yet, FA-mPEG-NPs still presented obvious cellular uptake similar to FA-NPs, indicating that PEG modification had minor influence on the FA receptor-mediated intracellular delivery process.


Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution.

Hou Z, Zhan C, Jiang Q, Hu Q, Li L, Chang D, Yang X, Wang Y, Li Y, Ye S, Xie L, Yi Y, Zhang Q - Nanoscale Res Lett (2011)

Confocal images. Confocal images of HeLa cells after incubated 24 h with different kinds of modified NPs at the same concentration 0.1 mg/ml; the nuclei were stained by DAPI (blue), and all of the NPs are labeled by rhodamine B (red). (a) Incubated with pure NPs; (b) incubated with FA-NPs; (c) incubated with mPEG-NPs; (d) incubated with mPEG-FA-NPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3306018&req=5

Figure 6: Confocal images. Confocal images of HeLa cells after incubated 24 h with different kinds of modified NPs at the same concentration 0.1 mg/ml; the nuclei were stained by DAPI (blue), and all of the NPs are labeled by rhodamine B (red). (a) Incubated with pure NPs; (b) incubated with FA-NPs; (c) incubated with mPEG-NPs; (d) incubated with mPEG-FA-NPs.
Mentions: To visualize the effect of FA-mediated endocytosis of different kinds of modified NPs, the distribution of rhodamine B-labeled NPs on HeLa cells was observed by confocal laser scanning microscopy (Figure 6). By 24-h incubation time, both FA-NPs and mPEG-FA-NPs show high intracellular rhodamine B concentration, which was visualized by red intensity of rhodamine B. Nevertheless, in case of mPEG-NPs, rhodamine B was significantly localized probably in the outside of the cells instead of a distribution in the endosomes, indicating that the mPEG-NPs tended to reduce the cell uptakes. In contrast, for blank NPs (Figure 6a), only low red intensity appeared in the peripheral region of the cells due to slow diffusion process into the cells for 24-h incubation period. NPs are generally internalized into cells via fluid phase endocytosis [26], phagocytosis [27], or receptor-mediated endocytosis [28]. Physicochemical characteristics such as particle size and surface properties played key roles in the cellular of NPs [29]. NP uptake could be considered as an adhesion process followed by an internalization process [30]. However, surface modification of NPs with PEG in our result seems to oppose uptake by the HeLa cells, which is mainly due to the formation of a dense, hydrophilic cloud of long flexible chains on the surface of the NPs that reduces the hydrophobic interactions with the membrane of tumor cells. The chemically anchored PEG chains can undergo spatial conformations, thus preventing the internalization of NPs by the cells. Yet, FA-mPEG-NPs still presented obvious cellular uptake similar to FA-NPs, indicating that PEG modification had minor influence on the FA receptor-mediated intracellular delivery process.

Bottom Line: Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group.In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release.Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Hospital, Xiamen University, Xiamen, 361003, China. Xly885@163.com.

ABSTRACT
Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments.

No MeSH data available.


Related in: MedlinePlus