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Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Alizadeh AM, Sadeghizadeh M, Najafi F, Ardestani SK, Erfani-Moghadam V, Khaniki M, Rezaei A, Zamani M, Khodayari S, Khodayari H, Mohagheghi MA - Biomed Res Int (2015)

Bottom Line: In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05).These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models.Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

ABSTRACT
Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

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Related in: MedlinePlus

Cytotoxic effects of PNPC on mouse mammary (4T1) and human hepatocellular (HuH-7) carcinoma cells. Cells were treated with different concentrations of PNPC for 24 h (a) and 48 h (b) on 4T1 cell line and 24 h (c) and 48 h (d) on HuH-7 cell line. Data reported are mean ± SD; *P < 0.05 compared to curcumin; PNPC = the polymeric nanoparticle curcumin; PNP = polymeric nanoparticles.
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fig5: Cytotoxic effects of PNPC on mouse mammary (4T1) and human hepatocellular (HuH-7) carcinoma cells. Cells were treated with different concentrations of PNPC for 24 h (a) and 48 h (b) on 4T1 cell line and 24 h (c) and 48 h (d) on HuH-7 cell line. Data reported are mean ± SD; *P < 0.05 compared to curcumin; PNPC = the polymeric nanoparticle curcumin; PNP = polymeric nanoparticles.

Mentions: PNPC significantly suppressed the proliferation of HuH-7 and 4T1 cancerous cells in a dose- and time-dependent manner in comparison with curcumin and PNP groups (P < 0.05). PNPC IC50 for 4T1 cells was 29 μM within 24 h (Figure 5(a)), which relatively reduced to 24 μM in 48 h (Figure 5(b)). In addition, PNPC IC50 for HuH-7 cells was 25 μM within 24 h (Figure 5(c)), which relatively reduced to 19 μM in 48 h (Figure 5(d)). We showed concentration about 48 and 40 μM for IC50 of free curcumin for 24 and 48 h, respectively. Therefore, we showed that IC50 of the free curcumin is significantly higher than PNPC, and PNPC significantly suppressed cell growth compared to free curcumin (P < 0.05). In addition, no significant toxicity was observed for void mPEG-OA nanocarrier (PNP) even at concentrations above the 40 μM. PNPC was not toxic to normal human fibroblastic cells (HFSF-PI3) [13], and this data is in accordance with other researcher results reviewed by Ravindran et al. [27]. PNPC showed nonsignificant changes in comparison with the positive control group. PNPC and doxorubicin had no effect on normal human fibroblasts cells (data not shown).


Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Alizadeh AM, Sadeghizadeh M, Najafi F, Ardestani SK, Erfani-Moghadam V, Khaniki M, Rezaei A, Zamani M, Khodayari S, Khodayari H, Mohagheghi MA - Biomed Res Int (2015)

Cytotoxic effects of PNPC on mouse mammary (4T1) and human hepatocellular (HuH-7) carcinoma cells. Cells were treated with different concentrations of PNPC for 24 h (a) and 48 h (b) on 4T1 cell line and 24 h (c) and 48 h (d) on HuH-7 cell line. Data reported are mean ± SD; *P < 0.05 compared to curcumin; PNPC = the polymeric nanoparticle curcumin; PNP = polymeric nanoparticles.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352453&req=5

fig5: Cytotoxic effects of PNPC on mouse mammary (4T1) and human hepatocellular (HuH-7) carcinoma cells. Cells were treated with different concentrations of PNPC for 24 h (a) and 48 h (b) on 4T1 cell line and 24 h (c) and 48 h (d) on HuH-7 cell line. Data reported are mean ± SD; *P < 0.05 compared to curcumin; PNPC = the polymeric nanoparticle curcumin; PNP = polymeric nanoparticles.
Mentions: PNPC significantly suppressed the proliferation of HuH-7 and 4T1 cancerous cells in a dose- and time-dependent manner in comparison with curcumin and PNP groups (P < 0.05). PNPC IC50 for 4T1 cells was 29 μM within 24 h (Figure 5(a)), which relatively reduced to 24 μM in 48 h (Figure 5(b)). In addition, PNPC IC50 for HuH-7 cells was 25 μM within 24 h (Figure 5(c)), which relatively reduced to 19 μM in 48 h (Figure 5(d)). We showed concentration about 48 and 40 μM for IC50 of free curcumin for 24 and 48 h, respectively. Therefore, we showed that IC50 of the free curcumin is significantly higher than PNPC, and PNPC significantly suppressed cell growth compared to free curcumin (P < 0.05). In addition, no significant toxicity was observed for void mPEG-OA nanocarrier (PNP) even at concentrations above the 40 μM. PNPC was not toxic to normal human fibroblastic cells (HFSF-PI3) [13], and this data is in accordance with other researcher results reviewed by Ravindran et al. [27]. PNPC showed nonsignificant changes in comparison with the positive control group. PNPC and doxorubicin had no effect on normal human fibroblasts cells (data not shown).

Bottom Line: In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05).These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models.Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

ABSTRACT
Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

Show MeSH
Related in: MedlinePlus