What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine

Abstract

Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specific cancer models. The role of zebrafish as a model for anticancer therapy studies has been highly evidenced, allowing researchers not only to perform drug screenings but also to evaluate novel therapies such as immunotherapies and nanotherapies. Beyond that, zebrafish can be used as an “avatar” model for performing patient-derived xenografts for personalized medicine. These characteristics place zebrafish in an attractive position as a role model for evaluating novel therapies for cancer treatment, such as nanomedicine.

Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer

“…As a result, we were able not only to observe how PNS behave in vivo, and how they interact with cancer cells, but also to confirm their stability and the maintenance of the association with NAs in an environment similar to that of patients. Our results are in line with several publications that use zebrafish as a model to evaluate nanomedicines (not for gene therapy purposes) and demonstrate how zebrafish can be used to evaluate novel cationic lipidic nanoemulsions in vivo with associated NAs (Sieber, Grossen, Bussmann, et al, 2019;Saez Talens et al, 2020;Rességuier et al, 2021;Cascallar et al, 2022).…”

“…Even though zebrafish is widely used as a model to evaluate therapies for cancer treatment ( Cascallar et al, 2022 ; Kwiatkowska et al, 2022 ), its use to develop and validate innovative gene therapy nanomedicines has not yet been fully investigated. With this aim, this work was carried out to demonstrate the potential of zebrafish as a key model in the study of new gene therapies based on nanotechnology.…”

“…Nevertheless, they entail certain disadvantages, including the high cost of maintenance and small progeny that prevents the possibility of carrying out large studies ( Lieschke and Currie, 2007a ; Sieber et al, 2019 ). A valuable alternative as an in vivo platform to evaluate the potential of nanomedicine is the zebrafish ( Gutiérrez-Lovera et al, 2017 ; Pearce et al, 2018 ; Sieber et al, 2019 ; Cascallar et al, 2022 ).…”

“…Based on these features, in the field of nanomedicine this model is being proposed to assess the biocompatibility and toxicity of several nanomaterials, but also to validate their therapeutic efficacy ( Gutiérrez-Lovera et al, 2017 ; Sieber, Grossen, Bussmann, et al, 2019 ; Wang et al, 2019 ; Pensado-López et al, 2021 ; Cascallar et al, 2022 ). The presence in zebrafish of organs and metabolic pathways analogous to those of humans allows toxicological and biocompatibility evaluations, and the large number of offspring enables high-throughput and multi- and transgenerational screens ( Horzmann and Freeman, 2018 ).…”

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

“…93 Overall, zebrafish embryos are nowadays recognized as a valuable model particularly suitable for the evaluation of nanotherapies. 4,[94][95][96][97] Some of the intrinsic characteristics of the model enable not only to perform toxicological assessment but also to perform functional assays and real-time monitoring of nanocarriers along the fish circulation. 4,98 For example, their transparency allows to visualize the biodistribution of fluorescent nanosystems or the real-time tracking of tumour growth.…”