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Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector.

Harris AN, Hinojosa BR, Chavious MD, Petros RA - Nanoscale Res Lett (2011)

Bottom Line: Metal release was a function of both pH and the presence of competing ligands.The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading.The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, University of North Texas, 1155 Union Circle, CB#305070, Denton, TX, 76203-5017, USA. petros@unt.edu.

ABSTRACT
The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

No MeSH data available.


Related in: MedlinePlus

In vitro toxicity of CuCNPs. (A) HeLa cell viability as measured via an assay based on MTT at 48 h showing toxicity only after the addition of Cu to the nanoparticles, (B) a similar experiment showing the reduced toxicity of CuCNPs upon reduction of Cu content.
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Figure 4: In vitro toxicity of CuCNPs. (A) HeLa cell viability as measured via an assay based on MTT at 48 h showing toxicity only after the addition of Cu to the nanoparticles, (B) a similar experiment showing the reduced toxicity of CuCNPs upon reduction of Cu content.

Mentions: The in vitro toxicity of CuCNPs in HeLa cells (a cervical adenocarcinoma) was investigated via an assay based on the MTT reagent (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide). Particles were added to wells with cells at the desired particle concentrations; the plates were incubated for 48 h, followed by an assessment of cell survival via the MTT reagent. Control particles (particles without added Cu) showed no toxicity up to the highest dosing. In contrast, Cu-loaded particles displayed significant toxicity with an IC50 of approximately 100 μg/mL (Figure 4A). The toxicity of free copper acetate was measured to allow for direct comparison with the amount of Cu contained in CuCNPs (see Additional file 4). We found that Cu contained in CuCNPs was significantly more toxic than an equivalent amount of free Cu dose, implying that the observed Cu toxicity was particle mediated. Finally, the amount of Cu loaded in CuCNPs was varied and its effect on toxicity investigated (Figure 4B). CuCNPs became significantly less toxic as the Cu loading was reduced, with little or no toxicity being observed for CuCNPs containing 3, or 5 wt.% Cu.


Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector.

Harris AN, Hinojosa BR, Chavious MD, Petros RA - Nanoscale Res Lett (2011)

In vitro toxicity of CuCNPs. (A) HeLa cell viability as measured via an assay based on MTT at 48 h showing toxicity only after the addition of Cu to the nanoparticles, (B) a similar experiment showing the reduced toxicity of CuCNPs upon reduction of Cu content.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211864&req=5

Figure 4: In vitro toxicity of CuCNPs. (A) HeLa cell viability as measured via an assay based on MTT at 48 h showing toxicity only after the addition of Cu to the nanoparticles, (B) a similar experiment showing the reduced toxicity of CuCNPs upon reduction of Cu content.
Mentions: The in vitro toxicity of CuCNPs in HeLa cells (a cervical adenocarcinoma) was investigated via an assay based on the MTT reagent (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide). Particles were added to wells with cells at the desired particle concentrations; the plates were incubated for 48 h, followed by an assessment of cell survival via the MTT reagent. Control particles (particles without added Cu) showed no toxicity up to the highest dosing. In contrast, Cu-loaded particles displayed significant toxicity with an IC50 of approximately 100 μg/mL (Figure 4A). The toxicity of free copper acetate was measured to allow for direct comparison with the amount of Cu contained in CuCNPs (see Additional file 4). We found that Cu contained in CuCNPs was significantly more toxic than an equivalent amount of free Cu dose, implying that the observed Cu toxicity was particle mediated. Finally, the amount of Cu loaded in CuCNPs was varied and its effect on toxicity investigated (Figure 4B). CuCNPs became significantly less toxic as the Cu loading was reduced, with little or no toxicity being observed for CuCNPs containing 3, or 5 wt.% Cu.

Bottom Line: Metal release was a function of both pH and the presence of competing ligands.The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading.The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chemistry, University of North Texas, 1155 Union Circle, CB#305070, Denton, TX, 76203-5017, USA. petros@unt.edu.

ABSTRACT
The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

No MeSH data available.


Related in: MedlinePlus