Jian-Ming Lü1, Zhengdong Liang1, Xiaoxiao Wang1, Jianhua Gu2, Qizhi Yao1,3, Changyi Chen1. 1. Division of Surgical Research, Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Plaza, Houston, TX 77030, USA. 2. AFM/SEM Core Facility, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA. 3. Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA.
Abstract
AIM: To develop an improved delivery system for nucleic acids. MATERIALS & METHODS: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEI polymer were determined. RESULTS: The new LGA-PEI polymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models. CONCLUSION: The new LGA-PEI polymer is a safer and more effective system to deliver DNA or RNA than PEI.
AIM: To develop an improved delivery system for nucleic acids. MATERIALS & METHODS: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEIpolymer were determined. RESULTS: The new LGA-PEIpolymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models. CONCLUSION: The new LGA-PEIpolymer is a safer and more effective system to deliver DNA or RNA than PEI.
Authors: Maria Camilla Operti; Yusuf Dölen; Jibbe Keulen; Eric A W van Dinther; Carl G Figdor; Oya Tagit Journal: Pharmaceutics Date: 2019-11-08 Impact factor: 6.321