In Vitro and Ex Vivo Anti-myeloma Effects of Nanocomposite AsS/ZnS/FeO

Overview

Journal Sci Rep

Specialty Science

Date 2022 Oct 27

PMID 36289430

Authors

Danka Cholujova

Lenka Koklesova

Zdenka Lukacova Bujnakova

Erika Dutkova

Zuzana Valuskova

Patricia Beblava

Anna Matisova

Jan Sedlak

Jana Jakubikova

Affiliations

Soon will be listed here.

Abstract

Nanoparticles in medicine can integrate actively targeted imaging agents and drug delivery vehicles, and combining multiple types of therapeutics in a single particle has numerous advantages, especially in multiple myeloma. MM is an incurable hematological disorder characterized by clonal proliferation of plasma cells in the bone marrow. In this study, we evaluated the anti-myeloma activity of 3 nanocomposites (3NPs): AsS/ZnS/FeO (1:4:1), AsS/ZnS/FeO with folic acid (FA), and AsS/ZnS/FeO with FA and albumin with reduced survival MM cell lines and primary MM samples by each of 3NP. Cytotoxic effects of 3NPs were associated with caspase- and mitochondria-dependent apoptosis induction and reduced c-Myc expression. Modulation of cell cycle regulators, such as p-ATM/ATM and p-ATR/ATR, and increases in p-Chk2, cyclin B1, and histones were accompanied by G/M arrest triggered by 3NPs. In addition, 3NPs activated several myeloma-related signaling, including JNK1/2/3, ERK1/2 and mTOR. To overcome BM microenvironment-mediated drug resistance, nanocomposites retained its anti-MM activity in the presence of stroma. 3NPs significantly decreased the stem cell-like side population in MM cells, even in the context of stroma. We observed strong synergistic effects of 3NPs combined with lenalidomide, pomalidomide, or melphalan, suggesting the potential of these combinations for future clinical studies.

Citing Articles

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PMID: 39384153 PMC: 11611669. DOI: 10.1016/j.jconrel.2024.10.003.

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