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

被引:75
作者
Tabatabaei, Seyed Nasrollah [1 ,2 ,3 ,4 ]
Derbali, Rabeb Mouna [5 ]
Yang, Chun [1 ,2 ,3 ]
Superstein, Rosanne [6 ]
Hamel, Patrick [6 ]
Chain, Jeanne Leblond [5 ]
Hardy, Pierre [1 ,2 ,3 ]
机构
[1] Univ Montreal, Dept Pediat, Montreal, PQ, Canada
[2] Univ Montreal, Dept Physiol, Montreal, PQ, Canada
[3] Univ Montreal, Dept Pharmacol, Montreal, PQ, Canada
[4] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Nanomed, Tehran, Iran
[5] Univ Montreal, Fac Pharm, Gene Delivery Lab, Montreal, PQ, Canada
[6] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada
关键词
Retinoblastoma; Melphalan; miR-181a; Liposomes; Lipid nanoparticles; Nanoparticles; Co-delivery technique; Complementary effect; Apoptosis; DRUG-DELIVERY; INTRAVITREAL MELPHALAN; LIPOSOMES; MICRORNAS; INJECTION; SIRNA; EYE; MICROPARTICLES; PROLIFERATION; INTRAARTERIAL;
D O I
10.1016/j.jconrel.2019.02.014
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Melphalan is an efficient chemotherapeutic agent that is currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and the hazardous integration of this drug in healthy cells is inevitable. MicroRNAs are short non-coding single-stranded RNAs that affect a vast range of biological processes. Previously, we focused on the regulatory role of miR-181a during cancer development and progression. In this manuscript, 171 nm switchable lipid nanoparticles (LNP) co-delivered melphalan and miR-181a with encapsulation efficiencies of 93%. Encapsulation of melphalan in LNP significantly improved its therapeutic efficiency. Gene analysis shows that miR-181a decreases the expression of anti-proliferative gene MAPK1 and antiapoptotic gene Bcl-2, but significantly increased the expression of pro-apoptotic gene BAX. Our results suggest that the two agents have a complementary effect in reducing the viability of cultured Rb cells (primary and cell line) and decreasing Rb cell counts in an in-vivo xenograft Rb model in rats. Our results suggest that the proposed co-delivery technique significantly increases the therapeutic impact, allows for lower administration of melphalan, and consequently, could minimize the cytotoxic side-effects of this drug.
引用
收藏
页码:177 / 185
页数:9
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