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Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid.

Li J, Chen T, Deng F, Wan J, Tang Y, Yuan P, Zhang L - Int J Nanomedicine (2015)

Bottom Line: Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface.Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups.Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis.

View Article: PubMed Central - PubMed

Affiliation: Chongqing Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

ABSTRACT
We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

No MeSH data available.


Related in: MedlinePlus

Effect of curcumin-induced apoptosis in HepG2 cells exposed to various formulations for 24 hours.Notes: (A) Control, (B) curcumin suspension, (C) curcumin-loaded albumin nanoparticles, (D) curcumin-loaded albumin nanoparticles surface-functionalized with GA, and (E) GA + curcumin-loaded albumin nanoparticles surface-functionalized with GA.Abbreviations: GA, glycyrrhetinic acid; PI, propidium iodide.
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f9-ijn-10-5475: Effect of curcumin-induced apoptosis in HepG2 cells exposed to various formulations for 24 hours.Notes: (A) Control, (B) curcumin suspension, (C) curcumin-loaded albumin nanoparticles, (D) curcumin-loaded albumin nanoparticles surface-functionalized with GA, and (E) GA + curcumin-loaded albumin nanoparticles surface-functionalized with GA.Abbreviations: GA, glycyrrhetinic acid; PI, propidium iodide.

Mentions: Apoptosis was determined using the Annexin V-fluorescein isothiocyanate detection kit to further validate the potential of Ccn-BNP-GA as a drug delivery agent specific for GA-positive cells. In Figure 9, Z1, Z2, Z3, and Z4 denote viable cells, early apoptotic cells, late apoptotic cells, and necrotic cells, respectively. The apoptosis rate is the total of Z2 and Z3. FCM with Annexin V-PI staining revealed that the apoptosis rate increased from 6.49% in the control group to 66.65% in the Ccn-BNP-GA group. The apoptosis rate for Ccn-BNP-GA was approximately twofold higher than that of Ccn suspension and Ccn-BNPs. As shown in Figure 9B and 9C, the proportion of viable cells decreased from 63.85% in the Ccn suspension group to 54.89% in the Ccn-BNP group, and the proportion of apoptotic cells were increased slightly from 35.82% to 45.00%. A competitive binding experiment was also conducted, and the results revealed that the apoptotic cells was gradually reduced by 35.12% when compared with Ccn-BNP-GA. These observations infer that Ccn-BNP-GA preferentially targeted GA receptors on the HepG2 cells.


Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid.

Li J, Chen T, Deng F, Wan J, Tang Y, Yuan P, Zhang L - Int J Nanomedicine (2015)

Effect of curcumin-induced apoptosis in HepG2 cells exposed to various formulations for 24 hours.Notes: (A) Control, (B) curcumin suspension, (C) curcumin-loaded albumin nanoparticles, (D) curcumin-loaded albumin nanoparticles surface-functionalized with GA, and (E) GA + curcumin-loaded albumin nanoparticles surface-functionalized with GA.Abbreviations: GA, glycyrrhetinic acid; PI, propidium iodide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556296&req=5

f9-ijn-10-5475: Effect of curcumin-induced apoptosis in HepG2 cells exposed to various formulations for 24 hours.Notes: (A) Control, (B) curcumin suspension, (C) curcumin-loaded albumin nanoparticles, (D) curcumin-loaded albumin nanoparticles surface-functionalized with GA, and (E) GA + curcumin-loaded albumin nanoparticles surface-functionalized with GA.Abbreviations: GA, glycyrrhetinic acid; PI, propidium iodide.
Mentions: Apoptosis was determined using the Annexin V-fluorescein isothiocyanate detection kit to further validate the potential of Ccn-BNP-GA as a drug delivery agent specific for GA-positive cells. In Figure 9, Z1, Z2, Z3, and Z4 denote viable cells, early apoptotic cells, late apoptotic cells, and necrotic cells, respectively. The apoptosis rate is the total of Z2 and Z3. FCM with Annexin V-PI staining revealed that the apoptosis rate increased from 6.49% in the control group to 66.65% in the Ccn-BNP-GA group. The apoptosis rate for Ccn-BNP-GA was approximately twofold higher than that of Ccn suspension and Ccn-BNPs. As shown in Figure 9B and 9C, the proportion of viable cells decreased from 63.85% in the Ccn suspension group to 54.89% in the Ccn-BNP group, and the proportion of apoptotic cells were increased slightly from 35.82% to 45.00%. A competitive binding experiment was also conducted, and the results revealed that the apoptotic cells was gradually reduced by 35.12% when compared with Ccn-BNP-GA. These observations infer that Ccn-BNP-GA preferentially targeted GA receptors on the HepG2 cells.

Bottom Line: Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface.Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups.Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis.

View Article: PubMed Central - PubMed

Affiliation: Chongqing Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

ABSTRACT
We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

No MeSH data available.


Related in: MedlinePlus