Co-delivery of miR-181a and melphalan by lipid nanoparticles for treatment of seeded retinoblastoma

• DOI: 10.1016/j.jconrel.2019.02.014
• Publication Date: 2019-02-15T07:42:15Z
• Authors: Seyed Nasrollah T...; Rabeb Mouna Derbali; Chun Yang; Rosanne Superstein; Patrick Hamel; Jeanne Leblond Chain; Pierre Hardy
• Keywords: Melphalan; Retinoblastoma; Viability assay

Melphalan is an efficient chemotherapeutic agent that currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and hazardous integration this drug in healthy cells inevitable. MicroRNAs are short non-coding single-stranded RNAs affect a vast range biological processes. Previously, we focused on regulatory role miR-181a during cancer development progression. In manuscript, 171 nm switchable lipid nanoparticles (LNP) co-delivered melphalan with encapsulation efficiencies 93%. Encapsulation LNP significantly improved its therapeutic efficiency. Gene analysis shows decreases expression anti-proliferative gene MAPK1 anti-apoptotic Bcl-2, but increased pro-apoptotic BAX. Our results suggest two agents have complementary effect reducing viability cultured Rb (primary cell line) decreasing counts in-vivo xenograft model rats. proposed co-delivery technique increases impact, allows for lower administration melphalan, consequently, could minimize cytotoxic side-effects drug.