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

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.

• Authors: Xiao Zheng, Fan Zhang, Yawei Zhao, Jing Zhang, Jianati Dawulieti, Yue Pan, Lianzhi Cui, Madi Sun, Dan Shao, Mingqiang Li, Kan He, Ming Zhang, Jing Li, Li Chen
• Journal: Theranostics (Theranostics) Vol. 8 Issue 14 Pg. 3808-3823 ( 2018) ISSN: 1838-7640 [Electronic] Australia
• PMID: 30083261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antagomirs
• Antineoplastic Agents
• MIRN27 microRNA, human
• MicroRNAs

Topics

• Animals
• Antagomirs (administration & dosage, analysis, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, analysis, pharmacokinetics)
• Cell Survival (drug effects)
• Disease Models, Animal
• Hep G2 Cells
• Heterografts
• Humans
• Liver Neoplasms (drug therapy)
• MicroRNAs (antagonists & inhibitors)
• Molecular Targeted Therapy (methods)
• Nanoparticles (administration & dosage, analysis)
• Neoplasm Transplantation
• Optical Imaging (methods)
• Theranostic Nanomedicine (methods)
• Treatment Outcome