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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

Release of Cu under various reaction conditions. (A) Initial release data simulating endosome/lysosome pH conditions, (B) release as a function of buffering species, (C) release as a function of added competing ligand, (D) release as a function of pH in the absence of competing ligand effects.
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Figure 3: Release of Cu under various reaction conditions. (A) Initial release data simulating endosome/lysosome pH conditions, (B) release as a function of buffering species, (C) release as a function of added competing ligand, (D) release as a function of pH in the absence of competing ligand effects.

Mentions: The applicability of CuCNPs for triggered release [1] has been studied by examining the rate of Cu release in response to changes in pH. Three identical samples of purified CuCNPs were dialyzed in either ultrapure water, 100 mM TRIS buffer at pH 7, or 100 mM citrate buffer at pH 5 and the release of Cu was monitored for 48 h by ICP MS (Figure 3A). Virtually no release was observed in ultrapure water with approximately 95% of the loaded Cu remaining bound to the particles over the course of the experiment. Cu release was observed at pH 7; however, release was much slower at this pH (particles at pH 7 had released approximately 55% of their Cu at 12 h) compared to pH 5. At pH 5, CuCNPs had released over 93% of their loaded Cu at 12 h, and at 48 h, complete release was observed. Cu weight percents determined by ICP MS at the end of this set of experiments were 12.1, 1.7, 0.0 wt.% Cu for CuCNPs dialyzed in ultrapure water, pH 7 buffer, and pH 5 buffer, respectively.


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)

Release of Cu under various reaction conditions. (A) Initial release data simulating endosome/lysosome pH conditions, (B) release as a function of buffering species, (C) release as a function of added competing ligand, (D) release as a function of pH in the absence of competing ligand effects.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Release of Cu under various reaction conditions. (A) Initial release data simulating endosome/lysosome pH conditions, (B) release as a function of buffering species, (C) release as a function of added competing ligand, (D) release as a function of pH in the absence of competing ligand effects.
Mentions: The applicability of CuCNPs for triggered release [1] has been studied by examining the rate of Cu release in response to changes in pH. Three identical samples of purified CuCNPs were dialyzed in either ultrapure water, 100 mM TRIS buffer at pH 7, or 100 mM citrate buffer at pH 5 and the release of Cu was monitored for 48 h by ICP MS (Figure 3A). Virtually no release was observed in ultrapure water with approximately 95% of the loaded Cu remaining bound to the particles over the course of the experiment. Cu release was observed at pH 7; however, release was much slower at this pH (particles at pH 7 had released approximately 55% of their Cu at 12 h) compared to pH 5. At pH 5, CuCNPs had released over 93% of their loaded Cu at 12 h, and at 48 h, complete release was observed. Cu weight percents determined by ICP MS at the end of this set of experiments were 12.1, 1.7, 0.0 wt.% Cu for CuCNPs dialyzed in ultrapure water, pH 7 buffer, and pH 5 buffer, respectively.

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