Autor: |
Dana Tarab‐Ravski, Inbal Hazan‐Halevy, Meir Goldsmith, Lior Stotsky‐Oterin, Dor Breier, Gonna Somu Naidu, Anjaiah Aitha, Yael Diesendruck, Brandon D. Ng, Hagit Barsheshet, Tamar Berger, Iuliana Vaxman, Pia Raanani, Dan Peer |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Advanced Science, Vol 10, Iss 21, Pp n/a-n/a (2023) |
Druh dokumentu: |
article |
ISSN: |
2198-3844 |
DOI: |
10.1002/advs.202301377 |
Popis: |
Abstract Multiple myeloma (MM) is a cancer of differentiated plasma cells that occurs in the bone marrow (BM). Despite the recent advancements in drug development, most patients with MM eventually relapse and the disease remains incurable. RNA therapy delivered via lipid nanoparticles (LNPs) has the potential to be a promising cancer treatment, however, its clinical implementation is limited due to inefficient delivery to non‐hepatic tissues. Here, targeted (t)LNPs designed for delivery of RNA payload to MM cells are presented. The tLNPs consist of a novel ionizable lipid and are coated with an anti‐CD38 antibody (αCD38‐tLNPs). To explore their therapeutic potential, it is demonstrated that LNPs encapsulating small interference RNA (siRNA) against cytoskeleton‐associated protein 5 (CKAP5) lead to a ≈90% decrease in cell viability of MM cells in vitro. Next, a new xenograft MM mouse model is employed, which clinically resembles the human disease and demonstrates efficient homing of MM cells to the BM. Specific delivery of αCD38‐tLNPs to BM‐residing and disseminated MM cells and the improvement in therapeutic outcome of MM‐bearing mice treated with αCD38‐tLNPs‐siRNA‐CKAP5 are shown. These results underscore the potential of RNA therapeutics for treatment of MM and the importance of developing effective targeted delivery systems and reliable preclinical models. |
Databáze: |
Directory of Open Access Journals |
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