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.
Original language | English |
---|---|
Article number | 2301377 |
Journal | Advanced Science |
Volume | 10 |
Issue number | 21 |
Early online date | 12 May 2023 |
DOIs | |
State | Published - 27 Jul 2023 |
Keywords
- BM niche
- MM murine model
- RNA therapy
- cancer
- lipid nanoparticles
- multiple myeloma
- targeted delivery
All Science Journal Classification (ASJC) codes
- General Engineering
- General Chemical Engineering
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- General Materials Science
- General Physics and Astronomy
- Medicine (miscellaneous)