Engineering multifunctional bioactive citric acid-based nanovectors for intrinsical targeted tumor imaging and specific siRNA gene delivery in vitro/in vivo

Min Wang; Yi Guo; Yumeng Xue; Wen Niu; Mi Chen; Peter X Ma; Bo Lei

doi:10.1016/j.biomaterials.2019.01.045

Engineering multifunctional bioactive citric acid-based nanovectors for intrinsical targeted tumor imaging and specific siRNA gene delivery in vitro/in vivo

Biomaterials. 2019 Apr:199:10-21. doi: 10.1016/j.biomaterials.2019.01.045. Epub 2019 Feb 2.

Authors

Min Wang¹, Yi Guo¹, Yumeng Xue¹, Wen Niu¹, Mi Chen¹, Peter X Ma², Bo Lei³

Affiliations

¹ Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China.
² Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2009, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109-1055, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA.
³ Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China; Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710054, China; Instrument Analysis Center, Xi'an Jiaotong University, Xi'an 710054, China. Electronic address: rayboo@xjtu.edu.cn.

PMID: 30731420
DOI: 10.1016/j.biomaterials.2019.01.045

Abstract

Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR also exhibited good blood compatibility and cell compatibility against C2C12, MCF-7 and A549. Compared with commercial transfection agent Lipofectamine™ 2000, PPFR had a high cellular uptake, equivalent transfection efficiency and effectively down-regulated intracellular p65 expression in A549 cancer cells. Importantly, PPFR could efficiently accumulate and label the tumor tissue through the fluorescent imaging, selectively deliver siRNA into tumor tissue in vivo based on the tumor-bearing nude mice model. This work may provide a facile strategy to synthesize multifunctional biocompatible biomaterials for targeted tumor imaging and gene therapy.

Keywords: Bioactive biomaterials; Citric acid-based polymers; Gene delivery; Module assembly; Photoluminescence; Targeted tumor bioimaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Biocompatible Materials / chemistry*
Cell Line, Tumor
Citric Acid / chemistry*
Diagnostic Imaging*
Fluorescence
Folic Acid / chemistry
Gene Silencing
Gene Transfer Techniques*
Humans
Luminescent Measurements
Mice, Inbred BALB C
Mice, Nude
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Nanotechnology*
Neoplasms / diagnostic imaging*
Neoplasms / pathology
Polyethyleneimine / chemistry
Proton Magnetic Resonance Spectroscopy
RNA, Small Interfering / administration & dosage*
Rats
Rhodamines / chemistry

Substances

Antineoplastic Agents
Biocompatible Materials
RNA, Small Interfering
Rhodamines
Citric Acid
Polyethyleneimine
Folic Acid
rhodamine B