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具有光致发光和可生物降解性的聚柠檬酸盐-聚乙二醇-聚乙烯亚胺聚合物作为高度生物相容性和高效的载体,用于生物成像引导的 siRNA 和 miRNA 递送。

Photoluminescent and biodegradable polycitrate-polyethylene glycol-polyethyleneimine polymers as highly biocompatible and efficient vectors for bioimaging-guided siRNA and miRNA delivery.

机构信息

Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710054, China.

Department of Biologic and Materials Sciences, Department of Biomedical Engineering, Macromolecular Science and Engineering Center, Department of Materials Science and Engineering, University of Michigan, Ann Arbor 48109, USA.

出版信息

Acta Biomater. 2017 May;54:69-80. doi: 10.1016/j.actbio.2017.02.034. Epub 2017 Feb 20.

DOI:10.1016/j.actbio.2017.02.034
PMID:28219808
Abstract

UNLABELLED

Development of biodegradable and biocompatible non-viral vectors with intrinsical multifunctional properties such as bioimaging ability for highly efficient nucleic acids delivery still remains a challenge. Here, a biodegradable poly (1,8-octanedio-citric acid)-co-polyethylene glycol grafted with polyethyleneimine (PEI) (POCG-PEI) polymers with the photoluminescent capacity were synthesized for nucleic acids delivery (siRNA and miRNA). POCG-PEI polymers can efficiently bind various nucleic acids, protect them against enzymatic degradation and release the genes in the presence of polyanionic heparin. POCG-PEI also showed a significantly low cytotoxicity, enhanced cellular uptake and high transfection efficiency of nucleic acids, as compared to commercial transfection agents, lipofectamine 2000 (Lipo) and polyethylenimine (PEI 25K). POCG-PEI polymers demonstrate an excellent photostability, which allows for imaging the cells and real-time tracking the nucleic acids delivery. The photoluminescent property, low cytotoxicity, biodegradation, good gene binding and protection ability and high genes delivery efficiency make POCG-PEI highly competitive as a non-virus vector for genes delivery and real-time bioimaging applications. Our results may be also an important step for designing biodegradable biomaterials with multifunctional properties towards bioimaging-guided genes therapeutic applications.

STATEMENT OF SIGNIFICANCE

Here, a biodegradable poly (1,8-octanedio-citric acid)-co-polyethylene glycol grafted with polyethyleneimine (PEI) (POCG-PEI) polymers with controlled photoluminescent capacity were synthesized for nucleic acids delivery (siRNA and miRNA). POCG-PEI polymers can efficiently bind various nucleic acids, protect them against enzymatic degradation and release the genes in the presence of polyanionic heparin. POCG-PEI also showed a significantly low cytotoxicity, enhanced cellular uptake and high transfection efficiency of nucleic acids, as compared to commercial transfection agents, lipofectamine 2000 (Lipo) and polyethylenimine (PEI 25K). POCG-PEI polymers demonstrate an excellent photostability, which allows for imaging the cells and real-time tracking the nucleic acids delivery. Our results may be also an important step for designing biodegradable biomaterials with multifunctional properties towards bioimaging-guided genes therapeutic applications.

摘要

未加标签

开发具有内在多功能特性的可生物降解和生物相容的非病毒载体,例如生物成像能力,对于高效核酸传递仍然是一个挑战。在这里,合成了具有光致发光能力的可生物降解的聚(1,8-辛二酸-柠檬酸)-共-聚乙二醇接枝聚乙烯亚胺(PEI)(POCG-PEI)聚合物,用于核酸传递(siRNA 和 miRNA)。POCG-PEI 聚合物可以有效地结合各种核酸,保护它们免受酶降解,并在带负电荷的肝素存在下释放基因。与商业转染试剂脂质体 2000(Lipo)和聚乙烯亚胺(PEI 25K)相比,POCG-PEI 还表现出显著降低的细胞毒性、增强的细胞摄取和核酸的高转染效率。POCG-PEI 聚合物具有优异的光稳定性,允许对细胞进行成像并实时跟踪核酸传递。光致发光特性、低细胞毒性、可生物降解性、良好的基因结合和保护能力以及高基因传递效率使 POCG-PEI 成为一种极具竞争力的非病毒载体,可用于基因传递和实时生物成像应用。我们的结果也可能是朝着生物成像引导基因治疗应用设计具有多功能特性的可生物降解生物材料的重要一步。

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