E-Book

E-Book 3rd Congress

  • SiRNA Delivery using Lipid-Polymer Nanoparticles to Target Cyclophilin A for the Treatment of Multiple Myeloma
  • Sina Eshaghi,1 Mohadeseh Ramezani,2 Mohammad Hossein Ahmadi,3,*
    1. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
    2. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
    3. Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.


  • Introduction: Multiple myeloma (MM) is a clonal plasma cell malignancy that forms solid tumors in the protective microenvironment of the bone marrow. After non-Hodgkin's lymphoma, this hematologic cancer is the second most common hematologic malignancy. Traditional treatment strategies for MMs include radiotherapy, chemotherapy, and stem cell transplantation. Although immunotherapy and cell therapy have also made significant progress in the last decade, nearly half of patients experience relapse or drug resistance. Therefore, there is a greater clinical need for innovative and more effective MM treatments. In this study, the use of a nanoparticle platform to deliver siRNA to the bone marrow endothelium to inhibit the secretion of cyclophilin A (CyPA) was investigated as a potential therapeutic approach to eliminate the colonization and proliferation of MM cells in the bone marrow.
  • Methods: In this review, articles were collected from PubMed, Scopus, and Google Scholar that were published between the years 2020 and 2023. These databases were searched using the keywords multiple myeloma, nanoparticle, SiRNA, and CyPA.
  • Results: Cyclophilin A (CyPA) is a homing factor secreted by bone marrow endothelial cells (BMECs). Investigations showed that CyPA inhibits implantation, proliferation, and colonization of MM cells in the bone marrow microenvironment and can be effective in drug resistance. This factor stimulates the migration of MM cells through the CD147 receptor. Recent studies have investigated how to engineer a potential therapeutic method that uses interfering RNA (iRNA) and nanoparticles to enter and target CyPA in the blood vessels of the bone marrow. This strategy inhibits CyPA in CEMBs. For this purpose, nanoparticles (with the combination of polymer-lipid or lipid-PEG) and siRNA are formulated through controlled mixing in a microfluidic device and enter the targeted tissue and subsequently the cell. In recent studies, several formulations of NP and siRNA combination have been analyzed. The results showed that with a certain formulation of the combination of nanoparticles and siCyPA and their entry into the endothelial cells of the bone marrow, it is possible to prevent the invasion of MM cells into the bone marrow and their spread.
  • Conclusion: The results of the studies show that siCyPA can inhibit the ability of MM cells to adhere and invade through BMEC monolayers. Overall, this study provides a combined therapeutic strategy to target the bone marrow microenvironment, rather than the cancer cells themselves, as a means to treat MM, which could be extended to the treatment of other hematologic malignancies, or malignancies that metastasize to bone.
  • Keywords: Multiple myeloma; nanoparticles; SiRNA; CyPA