Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model

Abstract

Oligonucleotide (ON) therapeutics are molecular target agents composed of chemically synthesized DNA or RNA molecules capable of inhibiting gene expression or protein function. How ON therapeutics can efficiently reach the inside of target cells remains a problem still to be solved in the majority of potential clinical applications. The chemical structure of ON compounds could affect their capability to pass through the plasma membrane. Other key factors are nuclease degradation in the extracellular space, renal clearance, reticulo-endothelial system, and at the target cell level, the endolysosomal system and the possible export via exocytosis. Several delivery platforms have been proposed to overcome these limits including the use of lipidic, polymeric, and inorganic nanoparticles, or hybrids between them. The possibility of evaluating the efficacy of the proposed therapeutic strategies in useful in vivo models is still a pivotal need, and the employment of zebrafish (ZF) models could expand the range of possibilities. In this review, we briefly describe the main ON therapeutics proposed for anticancer treatment, and the different strategies employed for their delivery to cancer cells. The principal features of ZF models and the pros and cons of their employment in the development of ON-based therapeutic strategies are also discussed.

Zebrafish: A Useful Animal Model for the Characterization of Drug-Loaded Polymeric NPs

“…On the other hand, this feature also represents a limitation. Indeed, due to the lack of an adaptative immune system in this developmental stage, which is a difference from other, more complex animal models, such as mice and rats, ZF embryos do not allow us to evaluate the key role of adaptive immunity in the tumor microenvironment and cancer progression [ 7 ].…”

“…ZF models are small and robust, cheap to maintain, and a single matching produces hundreds of eggs that develop extremely rapidly. An incomparable and unique feature is their optical transparency, which is important for easy visualization of the xenotransplanted cells or the biodistribution of the subject matter of research, or both simultaneously, with the aid of a fluorescence microscope and with high throughput results [ 7 ].…”

Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome

“…This successful discovery leads to the use of LNP to be drug delivery carriers for small molecules as well. [28]. Significantly, there are eight LNP structures approved by the FDA.…”

Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

“…Finally, it is worth mentioning that in the last decade, other animal models, such as zebrafish, gained great attention for the development of melanoma models. Zebrafish allow for high throughput in vivo studies [248,249,253], and furthermore, the peculiar transparency of zebrafish embryos allows for rapid visualization of fluorescently labelled melanoma cells, as well as of nanomedicines [246,247].…”