Nanomedicine is a new approach to fight against cancer by the development of anticancer nanoparticles (NPs) that are of high sensitivity, specificity, and targeting ability to detect cancer cells, such as the ability of Silica NPs in targeting epithelial cancer cells. However, these anticancer NPs require preclinical testing, and zebrafish is a useful animal model for preclinical studies of anticancer NPs. This model affords a large sample size, optical imaging, and easy genetic manipulation that aid in nanomedicine studies. This review summarizes the numerous advantages of the zebrafish animal model for such investigation, various techniques for inducing cancer in zebrafish, and discusses the methods to assess cancer development in the model and to test for the toxicity of the anticancer drugs and NPs. In addition, it summarizes the recent studies that used zebrafish as a model to test the efficacy of several different anticancer NPs in treating cancer.

Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells’ proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg/mL are non-toxic/non-cardio-toxic in the studied zebrafish xenograft model.

Tyrosine kinase inhibitors (TKIs) are new generation of anti-cancer drugs with very high efficiency against cancer cells. However, TKIs are associated with severe cardiotoxicity limiting their clinical benefits. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, PLGA-PEG-PLGA nanoparticles were synthesized to deliver Ponatinib while reducing its cardiotoxicity for treatment of chronic myeloid leukemia. Shape, size, surface charge and drug uptake ability of these nanoparticles were assessed using transmission electron microscopy (TEM), ZetaSIZER NANO and high-performance liquid chromatography (HPLC). Cardiotoxicity of Ponatinib, unloaded and loaded PLGA-PEG-PLGA nanoparticles were studied on zebrafish model through measuring the survival rate and cardiac function parameters, to optimize efficient drug concentrations in an in vivo setting. These particles were tested on zebrafish cancer xenograft model in which, K562 cell line, was transplanted into zebrafish embryos. We showed that, at an optimal concentration (0.0025mg/ml), Ponatinib loaded PLGA-PEG-PLGA particles are non-toxic/non-cardio-toxic and are very efficient against cancer growth and metastasis. Zebrafish is a good animal model for investigating the cardiotoxicity associated with the anti-cancer drugs such as TKIs, to determine the optimum concentration of smart nanoparticles with the least side effects and to generate xenograft model of several cancer types. Also, PLGA-PEG-PLGA NPs could be good candidate for CML treatment, but their cellular internalization should be enhanced. This could be achieved by coating and labeling the surface of PLGA-PEG-PLGA NPs with specific ligands that are unique to CML cells.