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.

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

Elena PEIRA
First
;
Daniela Chirio
;
Simona Sapino;Konstantin CHEGAEV;Giulia Chindamo;IRIS CHIARA SALAROGLIO;Chiara Riganti;Marina GALLARATE
2022-01-01

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.
2022
23
19
11555
11573
breast cancer cells; doxorubicin derivative; lipid nanoparticles; multi-drug resistance; osteosarcoma cells
Elena PEIRA; Daniela Chirio; Simona Sapino; Konstantin CHEGAEV; Giulia Chindamo; IRIS CHIARA SALAROGLIO; Chiara Riganti; Marina GALLARATE
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1885286
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