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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

Confocal laser scanning microscope images (a) and flow cytometric analysis (b). KB cells were treated with DOX or FAPuLG-2 nanoparticles. For blocking of the folate receptor of tumor cells, folic acid was pre-treated 1 h before drug or nanoparticle treatment.
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Fig5: Confocal laser scanning microscope images (a) and flow cytometric analysis (b). KB cells were treated with DOX or FAPuLG-2 nanoparticles. For blocking of the folate receptor of tumor cells, folic acid was pre-treated 1 h before drug or nanoparticle treatment.

Mentions: To test receptor-mediated delivery of drugs, DOX was used as a model drug because it has strong red fluorescence and can be used instead of a fluorescence marker. DOX-incorporated FAPuLG nanoparticles were studied using KB cells. Representative fluorescence images and flow cytometry results are depicted in Figure 5a,b, respectively. KB cells revealed strong red color when DOX or DOX-incorporated FAPuLG nanoparticles were treated, indicating that DOX or DOX-incorporated FAPuLG nanoparticles were entered into the tumor cells (Figure 5a). However, red fluorescence was decreased significantly when the folate receptor was blocked by pre-treatment with folic acid. These results indicated that nanoparticles of FAPuLG nanoparticles entered into the cells through folate-receptor-mediated endocytosis. Flow cytometry analysis also supported these results (Figure 5b), indicating that fluorescence intensity of KB cells was increased when DOX or DOX-incorporated nanoparticles were treated. Fluorescence intensity was decreased by the blocking of the folate receptor. Cell viability was checked to test receptor-mediated delivery of drug, and then, nanoparticles can selectively kill the tumor cells (Figure 6). Cell viability of FAPuLG nanoparticle treatment did not differ with the DOX values. However, viability of cell populations treated with FAPuLG nanoparticles increased when the folate receptor was blocked with folic acid. However, cell viability with DOX treatment was not significantly changed by blocking of folate receptor. These results indicated that FAPuLG nanoparticles can target the folate receptor of KB cells and selectively kill tumor cells.Figure 5


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)

Confocal laser scanning microscope images (a) and flow cytometric analysis (b). KB cells were treated with DOX or FAPuLG-2 nanoparticles. For blocking of the folate receptor of tumor cells, folic acid was pre-treated 1 h before drug or nanoparticle treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Confocal laser scanning microscope images (a) and flow cytometric analysis (b). KB cells were treated with DOX or FAPuLG-2 nanoparticles. For blocking of the folate receptor of tumor cells, folic acid was pre-treated 1 h before drug or nanoparticle treatment.
Mentions: To test receptor-mediated delivery of drugs, DOX was used as a model drug because it has strong red fluorescence and can be used instead of a fluorescence marker. DOX-incorporated FAPuLG nanoparticles were studied using KB cells. Representative fluorescence images and flow cytometry results are depicted in Figure 5a,b, respectively. KB cells revealed strong red color when DOX or DOX-incorporated FAPuLG nanoparticles were treated, indicating that DOX or DOX-incorporated FAPuLG nanoparticles were entered into the tumor cells (Figure 5a). However, red fluorescence was decreased significantly when the folate receptor was blocked by pre-treatment with folic acid. These results indicated that nanoparticles of FAPuLG nanoparticles entered into the cells through folate-receptor-mediated endocytosis. Flow cytometry analysis also supported these results (Figure 5b), indicating that fluorescence intensity of KB cells was increased when DOX or DOX-incorporated nanoparticles were treated. Fluorescence intensity was decreased by the blocking of the folate receptor. Cell viability was checked to test receptor-mediated delivery of drug, and then, nanoparticles can selectively kill the tumor cells (Figure 6). Cell viability of FAPuLG nanoparticle treatment did not differ with the DOX values. However, viability of cell populations treated with FAPuLG nanoparticles increased when the folate receptor was blocked with folic acid. However, cell viability with DOX treatment was not significantly changed by blocking of folate receptor. These results indicated that FAPuLG nanoparticles can target the folate receptor of KB cells and selectively kill tumor cells.Figure 5

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