Naked and Decorated Nanoparticles Containing H2S-Releasing Doxorubicin: Preparation, Characterization and Assessment of Their Antitumoral Efficiency on Various Resistant Tumor Cells

Abstract

Several semisynthetic, low-cardiotoxicity doxorubicin (DOXO) conjugated have been extensively described, considering the risk of cytotoxicity loss against resistant tumor cells, which mainly present drug efflux capacity. Doxorubicin 14-[4-(4-phenyl-5-thioxo-5H-[1,2]dithiol-3-yl)]-benzoate (H2S-DOXO) was synthetized and tested for its ability to overcome drug resistance with good intracellular accumulation. In this paper, we present a formulation study aimed to develop naked and decorated H2S-DOXO-loaded lipid nanoparticles (NPs). NPs prepared by the “cold dilution of microemulsion” method were decorated with hyaluronic acid (HA) to obtain active targeting and characterized for their physicochemical properties, drug entrapment efficiency, long-term stability, and in vitro drug release. Best formulations were tested in vitro on human-sensitive (MCF7) and human/mouse DOXO-resistant (MDA-MDB -231 and JC) breast cancer cells, on human (U-2OS) osteosarcoma cells and DOXO-resistant human/mouse osteosarcoma cells (U-2OS/DX580/K7M2). HA-decoration by HA-cetyltrimethyl ammonium bromide electrostatic interaction on NPs surface was confirmed by Zeta potential and elemental analysis at TEM. NPs had mean diameters lower than 300 nm, 70% H2S-DOXO entrapment efficiency, and were stable for almost 28 days. HA-decorated NPs accumulated H2S-DOXO in Pgp-expressing cells reducing cell viability. HA-decorated NPs result in the best formulation to increase the inter-cellular H2S-DOXO delivery and kill resistant cells, and therefore, as a future perspective, they will be taken into account for further in vivo experiments on tumor animal model.

Current approaches in tissue engineering-based nanotherapeutics for osteosarcoma treatment

“…Despite this, several investigations have revealed that OS patients may innately resist DOXO due to ATP-binding cassette transporter-mediated drug efflux [57,58]. Hence, the formulation and testing of naked and decorated H 2 S-DOXO-loaded lipid NPs against various cells, including DOXO-resistant human/mouse OS cells (U-2OS/DX580/K7M2), have elicited the inter-cellular drug delivery and increased cytotoxic effect towards resistant cells [59]. The manipulation through surface modifications, particularly with PEG, resulted in the controlled delivery of active ingredients from DOXO for an extended period [60].…”

Phytic acid-modified manganese dioxide nanoparticles oligomer for magnetic resonance imaging and targeting therapy of osteosarcoma

“…In recent years, various nanoformulations such as inorganic nanoparticles (NPs) (Li et al., 2020 ), liposomes (Jing et al., 2022 ), nanogel (Zhang et al., 2018 ), lipid NPs (Peira et al., 2022 ), and polymeric NPs (Heyder et al., 2021 ) had been widely exploited for targeting treatment of osteosarcoma (Ambrosio et al., 2021 ; Wu et al., 2022 ). Nanoformulations can target and deliver therapeutics to osteosarcoma region to improve therapeutic benefits and decrease adverse effects of therapeutics (Jo et al., 2015 ).…”

Nanotechnology in Targeted Drug Delivery

“…Reaching a therapeutic outcome that is able to fight neurodegenerative disorders, tumoral diseases, or immunological disorders is facilitated by an efficient and site-specific delivery of compounds. For these reasons, this Special Issue collates different aspects of research into nanotechnology in order to identify new therapeutic targets and strategies, including review papers [4,5], mathematical models to calculate the trajectories of magnetic NPs in the body or clarify the structures of metal-decorated fullerenes [6,7], the drug delivery systems of different antitumoral agents [8][9][10][11], and the biocompatibilities of stealth liposomes and hybrid nanosystems containing surfactant agents [12,13].…”