Theranostics 2018; 8(14):3808-3823. doi:10.7150/thno.25255

Research Paper

Self-assembled dual fluorescence nanoparticles for CD44-targeted delivery of anti-miR-27a in liver cancer theranostics

Xiao Zheng1, Fan Zhang1, Yawei Zhao1, Jing Zhang1, Jianati Dawulieti1, Yue Pan1, Lianzhi Cui4, Madi Sun1, Dan Shao1,3✉, Mingqiang Li3, Kan He1, Ming Zhang1, Jing Li1✉, Li Chen1,2✉

1. Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China
2. School of Nursing, Jilin University, Changchun 130021, China
3. Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
4. Clinical Laboratory, Jilin Cancer Hospital, Changchun 130012, China

Abstract

Despite the vital role miRNA-27a plays in driving the development and progress of liver cancer, miRNA-based inhibition therapy is hampered due to its undesired degradation and off-target effects. Herein, a multifunctional nanoparticle for noninvasive tracking of targeted delivery of anti-miR-27a oligonucleotides against liver cancer was constructed.

Methods: Dual-fluorescent conjugates (QD-HA-PEI) were first fabricated through crosslinking hyaluronic acid (HA), polyethyleneimine (PEI) and near-infrared (NIR) fluorescent quantum dots (QDs) via a facile one-pot approach. Antisense oligonucleotide was then encapsulated by QD-HA-PEI to form anti-miR-27a/QD-HA-PEI via electrostatic interactions. Targeting, biodistribution, bioimaging, in vitro cytotoxicity and in vivo anti-tumor effects were evaluated and the underlying mechanism was studied.

Results: The NIR fluorescence of anti-miR-27a/QD-HA-PEI could be employed to monitor CD44 receptor-targeted cellular uptake and tumor accumulation. Importantly, the intrinsic fluorescence of anti-miR-27a/QD-HA-PEI remained in the “ON” state in extracellular or blood environment, but switched to the “OFF” state in the intracellular environment, indicating pH-responsive oligonucleotide release. Furthermore, anti-miR-27a/QD-HA-PEI exhibited effective and selective anti-cancer effects in vitro and in vivo with fewer side effects via the direct down-regulation of oncogenic transcription factors FOXO1 and PPAR-γ.

Conclusion: Our findings validate the dual-fluorescent nanoparticles as delivery vectors of therapeutic miRNA, capable of simultaneous tumor imaging and tracking of miRNA-based modulation therapy, thereby providing an efficient and safe approach for liver cancer theranostics.

Keywords: Dual fluorescence, HA-PEI, anti-miR-27a, theranostics, liver cancer

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How to cite this article:
Zheng X, Zhang F, Zhao Y, Zhang J, Dawulieti J, Pan Y, Cui L, Sun M, Shao D, Li M, He K, Zhang M, Li J, Chen L. Self-assembled dual fluorescence nanoparticles for CD44-targeted delivery of anti-miR-27a in liver cancer theranostics. Theranostics 2018; 8(14):3808-3823. doi:10.7150/thno.25255. Available from http://www.thno.org/v08p3808.htm