In Vivo Toxicity Assessment of Hybrid Diatomite Nanovectors Using Hydra vulgaris as a Model System

Abstract

sulfuric acid, hydrogen peroxide, hydrochloride acid, ammonium hydroxide, and hydrofluoric acid). [4] Recent research proposed natural nanostructured silica from diatomite as a valid alternative to synthetic porous silica. [5] Diatomite is a fossil material, produced in tons by mining industry. Diatomite structure, mainly made of hydrated amorphous silica, exhibits a porous morphology with a relatively high specific surface area (30.92 m 2 g −1 ). [6] In the last years, porous micro-and nanoparticles obtained by diatomite were tailored as multifunctional scaffolds by using the standard chemistry of silica and tested as effective carriers of different drugs. [7,8] In these studies, extensive data on cytotoxicity of diatomite-based particles were reported by adopting in vitro techniques (e.g., 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide; adenosine triphosphate). Several cancer cell lines, such as colon cancer cells (Caco-2, HT-29, HCT-116), [9] human epidermoid cancer cells (H1355), [10] human breast cancer cells (MCF-7, MDA-MB-231), [11] murine A20 lymphoma cells, [12] and human cervix epithelioid carcinoma (HeLa) [13] were exposed to increasing concentrations (up to 400 µg mL −1 ) of diatomite micro-or nanoparticles up to 72 h, proving that the irregular shape of these new carriers did not affect cells proliferation or morphology and the hierarchical pore organization made them very suitable for drug delivery purposes. [10] These preliminary results represent only the first step for understanding if diatomite can be really considered a safe material for drug delivery. In vitro experimentation is the most prevalent scientific analysis used to verify NP toxicity effects. However, in vitro results may not always predict in vivo responses, where a variety of cell types and tissue connection govern cell and animal physiology. Additional in vivo tests, investigating the long-term effects of diatomite particles on a biological system and an eventual genotoxicity, are mandatory. In this work, we chose the cnidarian Hydra polyp, a simple freshwater invertebrate, as in vivo model system to understand the interaction between functionalized diatomite nanoparticles (DNPs) and a living organism, and to evaluate the consequent possible toxic effects, integrating animal, cell, and molecular biology approaches. Hydra vulgaris represents a valuable system to study the impact and toxicological effects of new nanomaterials at level of whole living organism. [14] Hydra consists of a cylindrical tubular body with a single apical opening (mouth) located into the head, surrounded by tentacles, and a foot presenting a basal disc that the polyp uses to anchor itself to a substrate. Hydra tissue is organized in two cell layers, an outer Drug nanocarriers based on nanostructured materials are very promising for precision and personalized medicine applications. Diatomite porous biosilica has been recently proposed as a novel and effective material in formulations of drug systems for oral and systemic delivery. In this paper,...

Time‐gated luminescence imaging of positively charged poly‐l‐lysine‐coated highly microporous silicon nanoparticles in living Hydra polyp

“…A, General scheme for toxicity score attribution according to Wilby's criterion (adapted from Reference [40]). B, Evaluation of toxicity of hPSiNPs and hPSiNPs‐PLL (in the latter case at different concentrations in order to establish the working conditions) at 2 hour incubation.…”

“…A nerve net throughout the body constitutes a simple nervous system [37]. Hydra is sensitive to a range of pollutants and has been used as a biological indicator of water pollution [38] as well as target for biocompatibility studies of functional nanomaterials [39,40]. The toxicity of a substance can be measured and quantified by monitoring the animal morphology over time and following a criterion given by Wilby's classification, which attributes to Hydra a score from 10 to 0 (from elongated tentacles and body to disintegrated appearance [41]) according to the degree of harmfulness.…”

Natural Diatom Biosilica as Microshuttles in Drug Delivery Systems

“…While surface coating with diatoms plays a crucial role in tissue integration, it was soon recognized that natural biosilica from diatoms also offers a promising biocompatible material for medicinal applications. In early 2019, Terracciano et al reported the in vivo compatibility and non-toxicity of diatom nanoparticles using a small invertebrate, the cnidarian freshwater polyp Hydra vulgaris , as an animal model [45]. Hydra polyps are highly sensitive to both organic and inorganic pollutants in their environment, leading in most cases to delayed growth, morphological changes, induction of apoptosis, and even alteration of gene expression [46,47].…”

Recent Advances on Diatom-Based Biosensors

“…Moreover, just like the porous silicon, the diatom frustules have remarkable optical properties that change on exposure to chemical substances [8,9,10,11,12,13,14,15,16]; their surface can be functionalized [17], and in conclusion, the diatom frustules have been considered as bio-derived transducers for biosensing applications [18]. In the last years, due to their unique characteristics, an increasing enthusiasm about the use of diatoms in nanotechnology has been registered in many important fields, from nanomedicine to environment monitoring [19,20,21,22,23,24,25,26,27,28,29,30,31]. Two books have been recently published in the area of diatoms, fixing the state of art in emerging applications [32,33].…”