Guojun Huang1, Qi Chen1, Wangteng Wu2, Jianwei Wang3, Paul K Chu4, Hongzhen Bai5, Guping Tang6. 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.
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.
Poor buffering capacity of chitosan (n class="Chemical">CS) results in insufficient intracellular gene release which poses the major barrier in gene delivery. Herein, we reconstructed pristine n>n class="Chemical">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.