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Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

Cabeza L, Ortiz R, Arias JL, Prados J, Ruiz Martínez MA, Entrena JM, Luque R, Melguizo C - Int J Nanomedicine (2015)

Bottom Line: The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects.The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX.Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain.

ABSTRACT
The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

No MeSH data available.


Related in: MedlinePlus

In vitro cytotoxicity of PBCA NPs in MCF-7 and E0771 cell lines.Notes: Growth of MCF-7 and E0771 cells was evaluated after 48 h of exposure to a wide range of PBCA NP concentrations (0.1–5.0 μM). Data represented as the mean value ± SD of quadruplicate cultures.Abbreviations: PBCA NPs, poly(butylcyanoacrylate) nanoparticles; SD, standard deviation; h, hours; NPs, nanoparticles.
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f2-ijn-10-1291: In vitro cytotoxicity of PBCA NPs in MCF-7 and E0771 cell lines.Notes: Growth of MCF-7 and E0771 cells was evaluated after 48 h of exposure to a wide range of PBCA NP concentrations (0.1–5.0 μM). Data represented as the mean value ± SD of quadruplicate cultures.Abbreviations: PBCA NPs, poly(butylcyanoacrylate) nanoparticles; SD, standard deviation; h, hours; NPs, nanoparticles.

Mentions: Before the antitumor tests, the toxicity of blank PBCA NPs (with no DOX loading) was investigated in MCF-7 and E0771 cells. No significant differences were observed between the negative control and the cells exposed to increasing concentrations of PBCA NPs (Figure 2). Thus, the lack of cytotoxicity of the PBCA NPs alone meant they could safely be used as drug carriers. On the other hand, the cytotoxicity of DOX-loaded PBCA NPs against MCF-7 breast carcinoma cells (IC50: 0.5 μM) was significantly greater than that of free DOX (IC50: 2 μM) (P<0.001) after 8 hours of incubation. This difference between the IC50 of DOX-loaded PBCA NPs and free DOX could still be observed after 48 hours of incubation (Figure 3A). In addition, the IC50 of DOX-loaded PBCA NPs in E0771 cells was significantly lower than the IC50 of the free antitumor drug (P<0.05). DOX loaded within PBCA NPs yielded an IC50 (0.2 μM) 15 times lower than that of free DOX (IC50: 3 μM) after 8 hours of exposure and 21.7 times lower (0.06 μM) after 48 hours of exposure (free DOX IC50: 1.3 μM) (Figure 3B).


Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

Cabeza L, Ortiz R, Arias JL, Prados J, Ruiz Martínez MA, Entrena JM, Luque R, Melguizo C - Int J Nanomedicine (2015)

In vitro cytotoxicity of PBCA NPs in MCF-7 and E0771 cell lines.Notes: Growth of MCF-7 and E0771 cells was evaluated after 48 h of exposure to a wide range of PBCA NP concentrations (0.1–5.0 μM). Data represented as the mean value ± SD of quadruplicate cultures.Abbreviations: PBCA NPs, poly(butylcyanoacrylate) nanoparticles; SD, standard deviation; h, hours; NPs, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4335619&req=5

f2-ijn-10-1291: In vitro cytotoxicity of PBCA NPs in MCF-7 and E0771 cell lines.Notes: Growth of MCF-7 and E0771 cells was evaluated after 48 h of exposure to a wide range of PBCA NP concentrations (0.1–5.0 μM). Data represented as the mean value ± SD of quadruplicate cultures.Abbreviations: PBCA NPs, poly(butylcyanoacrylate) nanoparticles; SD, standard deviation; h, hours; NPs, nanoparticles.
Mentions: Before the antitumor tests, the toxicity of blank PBCA NPs (with no DOX loading) was investigated in MCF-7 and E0771 cells. No significant differences were observed between the negative control and the cells exposed to increasing concentrations of PBCA NPs (Figure 2). Thus, the lack of cytotoxicity of the PBCA NPs alone meant they could safely be used as drug carriers. On the other hand, the cytotoxicity of DOX-loaded PBCA NPs against MCF-7 breast carcinoma cells (IC50: 0.5 μM) was significantly greater than that of free DOX (IC50: 2 μM) (P<0.001) after 8 hours of incubation. This difference between the IC50 of DOX-loaded PBCA NPs and free DOX could still be observed after 48 hours of incubation (Figure 3A). In addition, the IC50 of DOX-loaded PBCA NPs in E0771 cells was significantly lower than the IC50 of the free antitumor drug (P<0.05). DOX loaded within PBCA NPs yielded an IC50 (0.2 μM) 15 times lower than that of free DOX (IC50: 3 μM) after 8 hours of exposure and 21.7 times lower (0.06 μM) after 48 hours of exposure (free DOX IC50: 1.3 μM) (Figure 3B).

Bottom Line: The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects.The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX.Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain.

ABSTRACT
The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

No MeSH data available.


Related in: MedlinePlus