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

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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.


Representative optical images of zebrafish exposed to 0 (control) and 100 μg mL−1 of benz-CNOs and BODIPY-CNOs at 12, 48 and 96 hpf.Scale bars, 500 μm.Ch, chorion; E, eye; YS, yolk sac; H, heart; T, tail; F, finfold.
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f4: Representative optical images of zebrafish exposed to 0 (control) and 100 μg mL−1 of benz-CNOs and BODIPY-CNOs at 12, 48 and 96 hpf.Scale bars, 500 μm.Ch, chorion; E, eye; YS, yolk sac; H, heart; T, tail; F, finfold.

Mentions: Finally, the effects of CNOs on the organogenesis of zebrafish are evaluated. The embryos exposed to different CNO mass concentrations grow normally into the larval stage without signs of possible toxicity. Figure 4 shows the biocompatibility of CNOs as observed by the morphological development. Embryos imaged at 12, 48 (see Supplementary Figure S6) and 96 (see Supplementary Figure S7) hpf, corresponding respectively to segmentation, hatching and larvae stages, show negligible malformation. The noted malformations are yolk sac edema (YSE), pericardial edema (PCE), fin fold abnormalities (FF) and tail flexure (TF). In the embryos/larvae exposed to 50 and 100 μg mL−1 of benz-CNOs, there is a significant difference (p ≥ 0.01), for the FF and TF respectively (as shown in Fig. 5). Considering the BODIPY-CNOs, we observe a significant difference at 10 (FF), 50 (FF and TF), and 100 μg mL−1 (TF, FF, YSE, PCE). Nevertheless, the total percentages of abnormalities, induced by CNOs, are less than 4% (representing a score of 1 on a published 4-point malformation scale38).


Biocompatibility and biodistribution of functionalized carbon nano-onions (f-CNOs) in a vertebrate model
Representative optical images of zebrafish exposed to 0 (control) and 100 μg mL−1 of benz-CNOs and BODIPY-CNOs at 12, 48 and 96 hpf.Scale bars, 500 μm.Ch, chorion; E, eye; YS, yolk sac; H, heart; T, tail; F, finfold.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Representative optical images of zebrafish exposed to 0 (control) and 100 μg mL−1 of benz-CNOs and BODIPY-CNOs at 12, 48 and 96 hpf.Scale bars, 500 μm.Ch, chorion; E, eye; YS, yolk sac; H, heart; T, tail; F, finfold.
Mentions: Finally, the effects of CNOs on the organogenesis of zebrafish are evaluated. The embryos exposed to different CNO mass concentrations grow normally into the larval stage without signs of possible toxicity. Figure 4 shows the biocompatibility of CNOs as observed by the morphological development. Embryos imaged at 12, 48 (see Supplementary Figure S6) and 96 (see Supplementary Figure S7) hpf, corresponding respectively to segmentation, hatching and larvae stages, show negligible malformation. The noted malformations are yolk sac edema (YSE), pericardial edema (PCE), fin fold abnormalities (FF) and tail flexure (TF). In the embryos/larvae exposed to 50 and 100 μg mL−1 of benz-CNOs, there is a significant difference (p ≥ 0.01), for the FF and TF respectively (as shown in Fig. 5). Considering the BODIPY-CNOs, we observe a significant difference at 10 (FF), 50 (FF and TF), and 100 μg mL−1 (TF, FF, YSE, PCE). Nevertheless, the total percentages of abnormalities, induced by CNOs, are less than 4% (representing a score of 1 on a published 4-point malformation scale38).

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.