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Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer nanoparticles for folate-receptor-mediated drug delivery.

Lee SJ, Shim YH, Oh JS, Jeong YI, Park IK, Lee HC - Nanoscale Res Lett (2015)

Bottom Line: However, fluorescence intensity was decreased by blocking folate receptors.Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors.In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 501-746 Korea.

ABSTRACT

Background: Nanoparticles have been extensively investigated for targeted delivery of anticancer drugs. Since the folate receptor is universally over-expressed on the tumor cell membrane, folic acid is often used to modify the fate of nanoparticles in biologicals.

Methods: To fabricate targetable nanoparticles, folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3-cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG nanoparticles.

Results and discussion: Nanoparticles of FAPuLG copolymer that self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a model drug was incorporated into the FAPuLG nanoparticles that were used to treat folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy revealed that DOX-incorporated FAPuLG nanoparticles induced strong red fluorescence in the KB cells in the absence of folic acid. However, fluorescence intensity was decreased by blocking folate receptors. Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors. In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3.

Conclusions: The results indicate that FAPuLG nanoparticles can target the folate receptor of tumor cells. FAPuLG nanoparticles are a promising candidate for active targeting of anticancer agents.

No MeSH data available.


Related in: MedlinePlus

Synthesis scheme of FAPuLG copolymer (a)1H NMR spectra of FA-PU (b), PuLG (c), and FAPuLG (d) conjugates.
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Fig1: Synthesis scheme of FAPuLG copolymer (a)1H NMR spectra of FA-PU (b), PuLG (c), and FAPuLG (d) conjugates.

Mentions: Figure 1a depicts the synthesis scheme of the FAPuLG copolymer. Folic acid was conjugated to hydroxyl groups of pullulan using carbodiimide chemistry. Specific peaks of pullulan appeared between 3.0 ~ 5.8 ppm, and specific peaks of folic acid appeared at 6.5 ~ 9.0 ppm (Figure 1b). The substitution degree of folic acid against 100 glucose units of pullulan backbone was 9.88 and 35.8, respectively (Table 1). PLGA was also conjugated to FA-PU conjugates (Figure 1). The methylene proton of PLGA was appeared at 1.5 ppm (Figure 1d). These results indicated that FAPuLG copolymers were successively synthesized. Furthermore, PuLG copolymer without folic acid was synthesized for comparison and its characteristic peaks of pullulan and PLGA (Figure 1c). The substitution degree of folic acid and PLGA was calculated by 1H NMR spectra from known M.W.s of pullulan and PLGA [17]. Table 1 shows the characteristics of FAPuLG copolymer. The substitution degree of PLGA for PuLG, FAPuLG-1, and FAPuLG-2 was 1.27, 1.46, and 1.78, respectively.Figure 1


Folic-acid-conjugated pullulan/poly(DL-lactide-co-glycolide) graft copolymer nanoparticles for folate-receptor-mediated drug delivery.

Lee SJ, Shim YH, Oh JS, Jeong YI, Park IK, Lee HC - Nanoscale Res Lett (2015)

Synthesis scheme of FAPuLG copolymer (a)1H NMR spectra of FA-PU (b), PuLG (c), and FAPuLG (d) conjugates.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384989&req=5

Fig1: Synthesis scheme of FAPuLG copolymer (a)1H NMR spectra of FA-PU (b), PuLG (c), and FAPuLG (d) conjugates.
Mentions: Figure 1a depicts the synthesis scheme of the FAPuLG copolymer. Folic acid was conjugated to hydroxyl groups of pullulan using carbodiimide chemistry. Specific peaks of pullulan appeared between 3.0 ~ 5.8 ppm, and specific peaks of folic acid appeared at 6.5 ~ 9.0 ppm (Figure 1b). The substitution degree of folic acid against 100 glucose units of pullulan backbone was 9.88 and 35.8, respectively (Table 1). PLGA was also conjugated to FA-PU conjugates (Figure 1). The methylene proton of PLGA was appeared at 1.5 ppm (Figure 1d). These results indicated that FAPuLG copolymers were successively synthesized. Furthermore, PuLG copolymer without folic acid was synthesized for comparison and its characteristic peaks of pullulan and PLGA (Figure 1c). The substitution degree of folic acid and PLGA was calculated by 1H NMR spectra from known M.W.s of pullulan and PLGA [17]. Table 1 shows the characteristics of FAPuLG copolymer. The substitution degree of PLGA for PuLG, FAPuLG-1, and FAPuLG-2 was 1.27, 1.46, and 1.78, respectively.Figure 1

Bottom Line: However, fluorescence intensity was decreased by blocking folate receptors.Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors.In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 501-746 Korea.

ABSTRACT

Background: Nanoparticles have been extensively investigated for targeted delivery of anticancer drugs. Since the folate receptor is universally over-expressed on the tumor cell membrane, folic acid is often used to modify the fate of nanoparticles in biologicals.

Methods: To fabricate targetable nanoparticles, folic acid was conjugated to a pullulan backbone and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as FAPuLG) was conjugated. KB cells and NIH3T3-cell-bearing mice were prepared to prove folate receptor targeting of FAPuLG nanoparticles.

Results and discussion: Nanoparticles of FAPuLG copolymer that self-assembled in water were small with diameters <200 nm. Doxorubicin (DOX) as a model drug was incorporated into the FAPuLG nanoparticles that were used to treat folate receptor over-expressing KB human carcinoma cells. Fluorescence microscopy revealed that DOX-incorporated FAPuLG nanoparticles induced strong red fluorescence in the KB cells in the absence of folic acid. However, fluorescence intensity was decreased by blocking folate receptors. Antitumor activity of FAPuLG nanoparticles against KB cells in vitro was also decreased by blocking folate receptors. In animal study using near-infrared dye-conjugated FAPuLG nanoparticles, fluorescence intensity was significantly higher at KB solid tumor than that of NIH3T3.

Conclusions: The results indicate that FAPuLG nanoparticles can target the folate receptor of tumor cells. FAPuLG nanoparticles are a promising candidate for active targeting of anticancer agents.

No MeSH data available.


Related in: MedlinePlus