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Biocompatibility and biodistribution of functionalized carbon nano-onions (f-CNOs) in a vertebrate model

View Article: PubMed Central - PubMed

ABSTRACT

Functionalized carbon nano-onions (f-CNOs) are of great interest as platforms for imaging, diagnostic and therapeutic applications due to their high cellular uptake and low cytotoxicity. To date, the toxicological effects of f-CNOs on vertebrates have not been reported. In this study, the possible biological impact of f-CNOs on zebrafish during development is investigated, evaluating different toxicity end-points such as the survival rate, hatching rate, and heart beat rate. Furthermore, a bio-distribution study of boron dipyrromethene (BODIPY) functionalized CNOs in zebrafish larvae is performed by utilizing inverted selective plane illumination microscopy (iSPIM), due to its intrinsic capability of allowing for fast 3D imaging. Our in vivo findings indicate that f-CNOs exhibit no toxicity, good biocompatibility (in the concentration range of 5–100 μg mL−1) and a homogenous biodistribution in zebrafish larvae.

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Maximum intensity projections of the superior part (a) and tail (b) of treated larvae (100 μg mL-1 of BODIPY-CNOs. Exposure time: 200 ms, step size: 0.7 μm. Scale bars, 100 μm. E, eye; YS, yolk sac; T, tail; F, finfold.
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f6: Maximum intensity projections of the superior part (a) and tail (b) of treated larvae (100 μg mL-1 of BODIPY-CNOs. Exposure time: 200 ms, step size: 0.7 μm. Scale bars, 100 μm. E, eye; YS, yolk sac; T, tail; F, finfold.

Mentions: Figure 6a,b illustrate the in vivo distribution of green fluorescent CNOs in the zebrafish developed at complete organogenesis and exposed to 100 μg mL−1 mass concentrations of the BODIPY-CNO nanomaterial (z-stack images of Fig. 6a,b are reported as Supplementary Figure S8 and Figure S9). CNOs enter the embryos via chorion pores until 48–72 hpf by simply soaking of the embryos in the solution. After the hatching, zebrafish larvae took the CNOs up through both swallowing and skin-absorption63. As shown in Supplementary Figure S7, BODIPY-CNOs are present in the blood vessels, indicating that they are able to enter in the circulatory system and accumulate in different areas of the whole zebrafish. The BODIPY-CNOs exhibit a homogeneous distribution. In particular, Fig. 6a represents the 3D maximum projection of the upper part of the larvae, where the BODIPY-CNOs accumulate selectively in the head with the highest brightness at the retina level. This suggests a high affinity of CNOs for this tissue. Figure 6b reveals the green signal of the CNO immobilized BODIPY fluorophore throughout the whole trunk of the larvae. Such results indicate a ubiquitous distribution of the CNOs in the larvae’s body at 72 hpf.


Biocompatibility and biodistribution of functionalized carbon nano-onions (f-CNOs) in a vertebrate model
Maximum intensity projections of the superior part (a) and tail (b) of treated larvae (100 μg mL-1 of BODIPY-CNOs. Exposure time: 200 ms, step size: 0.7 μm. Scale bars, 100 μm. E, eye; YS, yolk sac; T, tail; F, finfold.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037369&req=5

f6: Maximum intensity projections of the superior part (a) and tail (b) of treated larvae (100 μg mL-1 of BODIPY-CNOs. Exposure time: 200 ms, step size: 0.7 μm. Scale bars, 100 μm. E, eye; YS, yolk sac; T, tail; F, finfold.
Mentions: Figure 6a,b illustrate the in vivo distribution of green fluorescent CNOs in the zebrafish developed at complete organogenesis and exposed to 100 μg mL−1 mass concentrations of the BODIPY-CNO nanomaterial (z-stack images of Fig. 6a,b are reported as Supplementary Figure S8 and Figure S9). CNOs enter the embryos via chorion pores until 48–72 hpf by simply soaking of the embryos in the solution. After the hatching, zebrafish larvae took the CNOs up through both swallowing and skin-absorption63. As shown in Supplementary Figure S7, BODIPY-CNOs are present in the blood vessels, indicating that they are able to enter in the circulatory system and accumulate in different areas of the whole zebrafish. The BODIPY-CNOs exhibit a homogeneous distribution. In particular, Fig. 6a represents the 3D maximum projection of the upper part of the larvae, where the BODIPY-CNOs accumulate selectively in the head with the highest brightness at the retina level. This suggests a high affinity of CNOs for this tissue. Figure 6b reveals the green signal of the CNO immobilized BODIPY fluorophore throughout the whole trunk of the larvae. Such results indicate a ubiquitous distribution of the CNOs in the larvae’s body at 72 hpf.

View Article: PubMed Central - PubMed

ABSTRACT

Functionalized carbon nano-onions (f-CNOs) are of great interest as platforms for imaging, diagnostic and therapeutic applications due to their high cellular uptake and low cytotoxicity. To date, the toxicological effects of f-CNOs on vertebrates have not been reported. In this study, the possible biological impact of f-CNOs on zebrafish during development is investigated, evaluating different toxicity end-points such as the survival rate, hatching rate, and heart beat rate. Furthermore, a bio-distribution study of boron dipyrromethene (BODIPY) functionalized CNOs in zebrafish larvae is performed by utilizing inverted selective plane illumination microscopy (iSPIM), due to its intrinsic capability of allowing for fast 3D imaging. Our in vivo findings indicate that f-CNOs exhibit no toxicity, good biocompatibility (in the concentration range of 5–100 μg mL−1) and a homogenous biodistribution in zebrafish larvae.

No MeSH data available.


Related in: MedlinePlus