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A Simple and Sensitive Method to Quantify Biodegradable Nanoparticle Biodistribution using Europium Chelates.

Crawford L, Higgins J, Putnam D - Sci Rep (2015)

Bottom Line: The TRF of the nanoparticles was found to diminish as a second order function in the presence of serum and tissue compositions interfered with the europium signal.Both phenomena were corrected by linearization of the signal function and calculation of tissue-specific interference, respectively.Overall, the method is simple and robust with a detection limit five times greater than standard fluorescent probes.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca NY.

ABSTRACT
The biodistribution of biodegradable nanoparticles can be difficult to quantify. We report a method using time resolved fluorescence (TRF) from a lanthanide chelate to minimize background autofluorescence and maximize the signal to noise ratio to detect biodegradable nanoparticle distribution in mice. Specifically, antenna chelates containing europium were entrapped within nanoparticles composed of polylactic acid-polyethylene glycol diblock copolymers. Tissue accumulation of nanoparticles following intravenous injection was quantified in mice. The TRF of the nanoparticles was found to diminish as a second order function in the presence of serum and tissue compositions interfered with the europium signal. Both phenomena were corrected by linearization of the signal function and calculation of tissue-specific interference, respectively. Overall, the method is simple and robust with a detection limit five times greater than standard fluorescent probes.

No MeSH data available.


Sensitivity analysis of (a) Eu(NTA)3 doped nanoparticles and (b) rhodamine B doped nanoparticles. Dotted lines correspond to the sensitivity limit. Eu(NTA)3 doped nanoparticles are more sensitive than rhodamine B doped nanoparticles. *Lowest concentration that is statistically different from sensitivity limit at p < 0.01.
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f2: Sensitivity analysis of (a) Eu(NTA)3 doped nanoparticles and (b) rhodamine B doped nanoparticles. Dotted lines correspond to the sensitivity limit. Eu(NTA)3 doped nanoparticles are more sensitive than rhodamine B doped nanoparticles. *Lowest concentration that is statistically different from sensitivity limit at p < 0.01.

Mentions: The sensitivity limit of the Eu(NTA)3 doped PLA-PEG NPs was determined and compared to RhoB loaded PLA-PEG NPs (Fig. 2). Encapsulation efficiencies were determined to be 87.0 ± 14% and 7.82 ± 1.7% for europium chelate and RhoB doped nanoparticles, respectively. Using the encapsulation efficiency, the europium doped NPs were detectable at as little as 8.7 × 10−6 mg/mL of europium chelate above the sensitivity limit compared to 3.9 × 10−5 mg/mL of RhoB for RhoB doped particles. This is an almost 5× increase in sensitivity using europium chelate doped nanoparticles over RhoB.


A Simple and Sensitive Method to Quantify Biodegradable Nanoparticle Biodistribution using Europium Chelates.

Crawford L, Higgins J, Putnam D - Sci Rep (2015)

Sensitivity analysis of (a) Eu(NTA)3 doped nanoparticles and (b) rhodamine B doped nanoparticles. Dotted lines correspond to the sensitivity limit. Eu(NTA)3 doped nanoparticles are more sensitive than rhodamine B doped nanoparticles. *Lowest concentration that is statistically different from sensitivity limit at p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561907&req=5

f2: Sensitivity analysis of (a) Eu(NTA)3 doped nanoparticles and (b) rhodamine B doped nanoparticles. Dotted lines correspond to the sensitivity limit. Eu(NTA)3 doped nanoparticles are more sensitive than rhodamine B doped nanoparticles. *Lowest concentration that is statistically different from sensitivity limit at p < 0.01.
Mentions: The sensitivity limit of the Eu(NTA)3 doped PLA-PEG NPs was determined and compared to RhoB loaded PLA-PEG NPs (Fig. 2). Encapsulation efficiencies were determined to be 87.0 ± 14% and 7.82 ± 1.7% for europium chelate and RhoB doped nanoparticles, respectively. Using the encapsulation efficiency, the europium doped NPs were detectable at as little as 8.7 × 10−6 mg/mL of europium chelate above the sensitivity limit compared to 3.9 × 10−5 mg/mL of RhoB for RhoB doped particles. This is an almost 5× increase in sensitivity using europium chelate doped nanoparticles over RhoB.

Bottom Line: The TRF of the nanoparticles was found to diminish as a second order function in the presence of serum and tissue compositions interfered with the europium signal.Both phenomena were corrected by linearization of the signal function and calculation of tissue-specific interference, respectively.Overall, the method is simple and robust with a detection limit five times greater than standard fluorescent probes.

View Article: PubMed Central - PubMed

Affiliation: School of Chemical and Biomolecular Engineering, Cornell University, Ithaca NY.

ABSTRACT
The biodistribution of biodegradable nanoparticles can be difficult to quantify. We report a method using time resolved fluorescence (TRF) from a lanthanide chelate to minimize background autofluorescence and maximize the signal to noise ratio to detect biodegradable nanoparticle distribution in mice. Specifically, antenna chelates containing europium were entrapped within nanoparticles composed of polylactic acid-polyethylene glycol diblock copolymers. Tissue accumulation of nanoparticles following intravenous injection was quantified in mice. The TRF of the nanoparticles was found to diminish as a second order function in the presence of serum and tissue compositions interfered with the europium signal. Both phenomena were corrected by linearization of the signal function and calculation of tissue-specific interference, respectively. Overall, the method is simple and robust with a detection limit five times greater than standard fluorescent probes.

No MeSH data available.