In-vitro and In-vivo Difference in Gene Delivery by Lithocholic Acid-polyethyleneimine Conjugate

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2019 Jun 30

PMID 31254934

Citations 22

Authors

Jianping Wang

Fanfei Meng

Bieong-Kil Kim

Xue Ke

Yoon Yeo

Affiliations

Soon will be listed here.

Abstract

Polyethyleneimine (PEI) is widely used for the delivery of nucleic acids, but its clinical application is limited due to high cytotoxicity and instability in biological fluids. To overcome these challenges, linear PEI (2.5 kDa) was modified with lithocholic acid (LCA) to produce a LCA-PEI conjugate (lp), and its complex with plasmid DNA (pDNA) was covered with hyaluronic acid (HA). Ternary complexes of pDNA, lp, and HA ("DlpH") were prepared in different ratios and tested in cells and tumor-bearing mice for gene transfection efficiency. DlpH with a relatively high lp/pDNA ratio (Hi-DlpH) was more resistant to DNase and heparin treatment and showed more efficient gene transfection than DlpH with a lower lp/pDNA ratio (Lo-DlpH) in vitro. In contrast, Hi- and Lo-DlpH showed distinct transfection efficiency in vivo in a tumor-size dependent manner, where Hi-DlpH showed relatively high gene transfection in tumors of <300 mm but performed poorly in tumors of >500 mm and Lo-DlpH did the opposite. Tumor-associated macrophages, which increase with tumor growth and preferentially intercept Hi-DlpH, may account for the poor performance of Hi-DlpH in relatively large tumors. Accordingly, suggestions are made for future in vitro screening of new gene formulations to better predict their in vivo performances.

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