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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

Cu-loading chemistry for CuCNPs (left) and the structure of dinuclear Cu2(OAc)4(H2O)2 (right).
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Figure 1: Cu-loading chemistry for CuCNPs (left) and the structure of dinuclear Cu2(OAc)4(H2O)2 (right).

Mentions: Cu2+ loading to form Cu-loaded carboxylate-functionalized nanoparticles (CuCNPs) was accomplished by first adjusting the pH of the particle-containing solution to 7.0 using 1.0 M NaOH, which deprotonated the carboxylic acid groups, followed by the addition of CuSO4 in a 1:1 molar ratio to NaOH (Figure 1). The representation shown in Figure 1 for Cu binding to CuCNPs represents a mononuclear complex; however, a dinuclear complex like that observed for molecular copper acetate (also shown in Figure 1) is equally likely (note: the schematic in Figure 1 shows carboxylic acid groups only on the surface of the particle; however, the particle is a porous hydrogel, which allows copper to freely diffuse throughout the polymer network and bind to carboxylate groups on the interior of the particle as well). The particle solution was then dialyzed to remove unbound copper. Particle size of approximately 215 nm in solution was determined via dynamic light scattering (see Additional file 1) and a scanning electron microscope (SEM) image of dried CuCNPs is shown in Figure 2A.


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)

Cu-loading chemistry for CuCNPs (left) and the structure of dinuclear Cu2(OAc)4(H2O)2 (right).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Cu-loading chemistry for CuCNPs (left) and the structure of dinuclear Cu2(OAc)4(H2O)2 (right).
Mentions: Cu2+ loading to form Cu-loaded carboxylate-functionalized nanoparticles (CuCNPs) was accomplished by first adjusting the pH of the particle-containing solution to 7.0 using 1.0 M NaOH, which deprotonated the carboxylic acid groups, followed by the addition of CuSO4 in a 1:1 molar ratio to NaOH (Figure 1). The representation shown in Figure 1 for Cu binding to CuCNPs represents a mononuclear complex; however, a dinuclear complex like that observed for molecular copper acetate (also shown in Figure 1) is equally likely (note: the schematic in Figure 1 shows carboxylic acid groups only on the surface of the particle; however, the particle is a porous hydrogel, which allows copper to freely diffuse throughout the polymer network and bind to carboxylate groups on the interior of the particle as well). The particle solution was then dialyzed to remove unbound copper. Particle size of approximately 215 nm in solution was determined via dynamic light scattering (see Additional file 1) and a scanning electron microscope (SEM) image of dried CuCNPs is shown in Figure 2A.

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