A novel potential biocompatible hyperbranched polyspermine for efficient lung cancer gene therapy.

Abstract

The clinical successful application of gene therapy critically depends upon the development of non-toxic and efficient delivery system. Although polycationic non-viral vectors hold great promise in nanomedicine, the exploring of application in clinics still remains a big challenge. To develop a non-toxic and efficient non-viral gene delivery system, two kinds of endogenous substance, citric acid (CA) and spermine (SPE), were used to prepare a new low charge density hyperbranched polyspermine (HPSPE) by one-pot polymerization. The biocompatibility evaluated by hemolytic activity and red blood cell (RBC) aggregation indicated that HPSPE was highly biocompatible without causing hemolysis and RBC aggregation compared with PEI as well as SPE. The MTS assay also demonstrated that the cell viability of HPSPE was above 90% even at 200 μg/mL at different time (24 and 72 h), which much higher than PEI 25K. Besides, HPSPE showed high transfection efficiency without any toxic effect after aerosol delivery to the mice. Moreover, aerosol delivery of HPSPE/Akt1 shRNA significantly reduced tumor size and numbers and efficiently suppressed lung tumorigenesis ultimately in K-ras(LA1) lung cancer model mice. These results suggest that low charge density as well as endogenous substance skeleton endow HPSPE with great potential for toxicity-free and efficient gene therapy.

• Authors: Rong-Lin Xie, Yoon-Jeong Jang, Lei Xing, Bing-Feng Zhang, Feng-Zhen Wang, Peng-Fei Cui, Myung-Haing Cho, Hu-Lin Jiang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 478 Issue 1 Pg. 19-30 (Jan 15 2015) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 25448566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Small Interfering
• Green Fluorescent Proteins
• Citric Acid
• Spermine
• DNA
• Akt1 protein, mouse
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Citric Acid (chemistry)
• DNA (administration & dosage)
• Erythrocytes (drug effects, pathology)
• Gene Transfer Techniques
• Green Fluorescent Proteins (genetics, metabolism)
• Hemolysis (drug effects)
• Humans
• Lung Neoplasms (metabolism, pathology, therapy)
• Male
• Mice, Inbred C57BL
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Small Interfering (administration & dosage)
• Rats
• Spermine (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Tumor Burden (drug effects)