Reduction sensitive CC9-PEG-SSBPEI/miR-148b nanoparticles: synthesis, characterization, targeting delivery and application for anti-metastasis

Abstract miRNAs such as miR-148b play crucial regulatory role in tumor metastasis, but their applications are limited because they are easy to degrade in serum conditions and lack targeting ability. Herein, CC9-PEG-SSBPEI was synthesized and used as nano-carrier for miR-148b. DLS and gel retardation analyses indicated that CC9-PEG-SSBPEI could combine with miR-148b by charge interaction and formed into nanoparticles with the size changed from 811.6 nm to 146.4 nm. CC9-PEG-SSBPEI could protect miR-148b from RNase A degradation and showed a reduction sensitive release of miR-148b. FACS analysis and CLSM images displayed that the conjugated CC9 peptide improved the accumulation and penetration of the nanoparticles in HuH-7 liver cancer cells through binding with the target of miR-148b neuropilin-1(NRP-1) on the cell surface. The raised level of miR-148b in turn inhibited the expression of NRP-1 and suppressed the migration of HuH-7 liver cancer cells. Moreover, hemolysis and cytotoxicity assay demonstrated that the nanoparticles had good hemo- and cyto- compatibility. Hence, CC9-PEG-SSBPEI/miR-148b nanoparticles had the potential for targeting delivery of miR-148b and anti-metastasis of hepatocellular carcinoma (HCC) cells.