PK11195-chitosan-graft-polyethylenimine-modified SPION as a mitochondria-targeting gene carrier

Abstract

Superparamagnetic iron oxide nanoparticle (SPION) holds great potential as a gene delivery system due to its unique properties, such as good biocompatibility and non-invasive targeting ability. In this study, we modified SPION with chitosan-graft-PEI (CHI-g-PEI) and PK11195, to fabricate a mitochondria-targeting gene carrier, PK-CP-SPION. PK-CP-SPION manifested prominent physicochemical properties for magnetic guided gene delivery, and it could effectively condense and protect DNA at proper weight ratios. The in vitro cytotoxicity of PK-CP-SPIONs was mild. Under an external magnetic field, the transfection efficiency of PK-CP-SPIONs was comparable to PEI 25 K with shorter transfection time. PK11195 facilitated the specific accumulation of PK-CP-SPIONs in mitochondria, leading to the leakage of cytochrome c, the dissipation of mitochondrial membrane potential and subsequently the activation of mitochondria apoptosis pathway. These results indicated that with further development, PK-CP-SPIONs could serve as a multifunctional nanoplatform for magnetic targeting gene delivery and mitochondria-targeting therapy, leading enhanced therapeutic effect towards tumor cells.

• Gene therapy
• magnetofection
• mitochondria-targeting
• non-viral vector
• superparamagnetic iron oxide nanoparticles

Declaration of interest

The authors report no conflicts of interest in this work.

This work was supported by the Funds for Creative Research Groups of China, National Natural Science Foundation of China (No. 81421005) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Part of this work was supported by the Jiangsu Province Public Technology Service Center of Nanodrug Preparation and Evaluation. Part of this work was also supported by the National Natural Science Foundation of China (Grant No. 81573369 and 21301191) the Natural Science Foundation of Jiangsu Province (Grant No. BK20130661 and BK20140659).