Self-assembled nanoparticles for cellular delivery of peptide nucleic acid using amphiphilic N,N,N-trimethyl-O-alkyl chitosan derivatives |
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| Authors: | Chundong Liu Jianhua Wang Sheng Huang Lin Yu Yan Wang Hang Chen Dong Wang |
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| Affiliation: | 1.Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering,Chongqing University,Chongqing,China |
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| Abstract: | ![]()
Peptide nucleic acid (PNA) holds enormous potentials as antisense/antigenic drug due to its specific binding ability and biostability with DNA or RNA. However, the poor cellular delivery is the key obstacle in development of PNA therapy. To overcome this difficulty, we developed self-assembled nanoparticles (NPs) for delivery of PNA to living cells using amphiphilic CS derivatives. A series of N,N,N-trimethyl-O-alkyl chitosans (TMACs) with different lengths of alkyl chains were synthesized. The structures of these synthesized chemicals were characterized with FT-IR and 1H NMR. We found that the TMACs were all able to self-assemble in aqueous condition to form nano-size NPs. These nano-size NPs are spherical shape with a size range of around 100?nm and a zeta potential above +30?mV. PNA was easily encapsulated into chitosan derivative NPs by an ultrasonic method with entrapment efficiency up to 75%. The PNA-loaded TMAC NPs released the drug in a sustained manner in PBS (pH 7.4) at 37?°C. N,N,N-trimethyl-O-cetyl chitosan (TMCC) showed the best in vitro hemocompatibility and cell viability. These TMCC based NPs were able to dramatically increase the cellular uptake of PNA, specifically, 66-fold higher compared to without using these nanoparticles. The results suggest that the designed TMCC NPs might be a promising solution for improving cellular delivery of PNA. | |
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