Reconstructed chitosan with alkylamine for enhanced gene delivery by promoting endosomal escape

Guojun Huang; Qi Chen; Wangteng Wu; Jianwei Wang; Paul K Chu; Hongzhen Bai; Guping Tang

doi:10.1016/j.carbpol.2019.115339

Reconstructed chitosan with alkylamine for enhanced gene delivery by promoting endosomal escape

Carbohydr Polym. 2020 Jan 1:227:115339. doi: 10.1016/j.carbpol.2019.115339. Epub 2019 Sep 19.

Authors

Guojun Huang¹, Qi Chen¹, Wangteng Wu², Jianwei Wang³, Paul K Chu⁴, Hongzhen Bai⁵, Guping Tang⁶

Affiliations

¹ Department of Chemistry, Zhejiang University, Hangzhou 310028, China; Department of Physics and Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
² Department of Chemistry, Zhejiang University, Hangzhou 310028, China; School of Medicine, Zhejiang University, Hangzhou 310019, China.
³ Department of Chemistry, Zhejiang University, Hangzhou 310028, China.
⁴ Department of Physics and Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
⁵ Department of Chemistry, Zhejiang University, Hangzhou 310028, China. Electronic address: hongzhen_bai@zju.edu.cn.
⁶ Department of Chemistry, Zhejiang University, Hangzhou 310028, China; Department of Physics and Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China. Electronic address: tangguping@zju.edu.cn.

PMID: 31590870
DOI: 10.1016/j.carbpol.2019.115339

Abstract

Poor buffering capacity of chitosan (CS) results in insufficient intracellular gene release which poses the major barrier in gene delivery. Herein, we reconstructed pristine CS with propylamine (PA), (diethylamino) propylamine (DEAPA), and N, N-dimethyl- dipropylenetriamine (DMAMAPA) to obtain a series of alkylamine-chitosan (AA-CS). The introduction of multiple amino groups with rational ratios functionally enhance the buffering capacity of AA-CS, among which DMAPAPA-CS showed buffering capacity of 1.58 times that of chitosan. The reconstructed AA-CS functionally enhance the ability of gene binding and endosomal escape. It was observed that the DMAPAPA-CS/pDNA complexes exhibit a notable gene delivery efficiency, which promotes the functionalization of loaded pDNA. Importantly, the in vivo delivery assay reveals that the deep penetration issue can be resolved using DMAPAPA-CS gene delivery vector. Finally, the DMAPAPA-CS is applied to deliver the therapeutic p53 gene in A549 bearing mice, showing efficient therapeutic potential for cancer.

Keywords: Alkylamine; Buffering capacity; Chitosan; Endosomal escape; Gene delivery.

MeSH terms

A549 Cells
Amines / administration & dosage*
Amines / chemistry
Amines / pharmacokinetics
Animals
Cell Survival / drug effects
Chitosan / administration & dosage*
Chitosan / chemistry
Chitosan / pharmacokinetics
DNA / administration & dosage*
DNA / chemistry
Endocytosis
Endosomes*
Erythrocytes / drug effects
Female
Gene Transfer Techniques*
HEK293 Cells
Hemolysis / drug effects
Humans
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Lung Neoplasms / therapy
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / chemistry
RNA, Small Interfering / pharmacokinetics
Tumor Suppressor Protein p53 / genetics*

Substances

Amines
RNA, Small Interfering
Tumor Suppressor Protein p53
DNA
Chitosan