Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine-Modified Gelatin Nanoparticles.

Tzu-Ting Hung,Hsing-Yi Yu,Ming-Ju Chou,Jui-Ching Hsia,Edward Chern,Hsiao-Mei Chao,Ying-Hou Chen,Yi-You Huang

doi:10.3390/ma11020301

Abstract

Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.

Highlights

Intracellular functional proteins, such as specific transcriptional factors or epigenetic modulators, may trigger cell fate transition/cell reprogramming during development and pathophysiological processes.Recently, several studies showed that cell reprogramming may be a new approach for regenerative medicine and disease therapy
We showed that polyethyleneimine (PEI)-modified Gelatin nanoparticles (GNPs) could deliver DNA/plasmid with high efficiency in vivo and in vitro [17]
Discussion intracellular functional protein delivery by nano/micro carriers has become more important for biomedical application, such as cell reprogramming in regenerative medicine, cell fate transition, and cancer differentiation therapy

Summary

Introduction

Intracellular functional proteins, such as specific transcriptional factors or epigenetic modulators, may trigger cell fate transition/cell reprogramming during development and pathophysiological processes. Several studies showed that cell reprogramming may be a new approach for regenerative medicine and disease therapy. In 2006, Yamanaka et al transduced the transcription factors Oct, Sox. C-Myc with a retroviral system to induce fibroblasts to change their cell fate into a pluripotent state and generated induced pluripotent stem cells [1]. Liver fibrosis is a chronic inflammatory disease and severe liver fibrosis may lead toward liver cancer. Liver fibrosis is caused by hepatic stellate cell activation and extracellular matrix accumulation in the liver.

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Results

Conclusion