A recent study conducted by the University of Pennsylvania, Philadelphia, has shown promising results in reducing tumor burden and improving the survival rates of multiple myeloma patients. The researchers utilized siRNA-based silencing of Cyclophilin A (CyPA), a protein associated with tumor progression and chemotherapeutic resistance in bone marrow endothelial cells. This targeted nanoparticle delivery system has the potential to revolutionize multiple myeloma therapy.
Published in the prestigious journal PNAS, the paper titled “In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles for multiple myeloma therapy” describes the successful delivery of nucleic acid therapeutics to bone marrow endothelial cells using a nanoparticle platform. Multiple myeloma is a currently incurable blood cancer that primarily affects the bone marrow, with limited survival rates for patients.
By inhibiting CyPA and making the cancer cells more susceptible to chemotherapy, the researchers were able to hinder the progression of multiple myeloma. However, delivering inhibiting molecules to the bone marrow endothelium has always been a challenge.
Small interfering RNA (siRNA) therapeutics have shown great potential in silencing specific genes associated with diseases. In this study, the researchers developed nanoparticles that could encapsulate siRNA and protect it from degradation in the bloodstream. The functionalization of the nanoparticle surface chemistry enabled specific tissue targeting.
In a live mouse model, the nanoparticle delivery system successfully silenced CyPA, reducing multiple myeloma invasion and disrupting interactions with bone marrow endothelial cells. When combined with the therapeutic drug bortezomib, CyPA silencing sensitized cancer cells to treatment, reducing proliferation and angiogenesis, and ultimately prolonging mouse survival.
This groundbreaking study suggests that the nanoparticle platform developed by the research team could be applied to other malignancies, providing a potential breakthrough in the delivery of nucleic acid therapeutics.
More information:
Pedro P. G. Guimarães et al, In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles for multiple myeloma therapy, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2215711120
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Nanoparticles deliver small interfering RNA to slow multiple myeloma (2023, June 17)
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