title: Biodegradable Multiamine Polymeric Vector for siRNA Delivery.
abstract: The gene silencing activity of small interfering RNA (siRNA) has led to their use as tools for target validation and as potential therapeutics for a variety of diseases. A major challenge is the development of vectors with high delivery efficiency and low toxicity. Although poly(ethylenimine) (PEI) has been regarded as the most promising polymeric vector for nucleic acid delivery, the nonbiodegradable structure greatly hinders its clinical application. In the present study, a diblock copolymer, PEG-PAsp(DIP-DETA), of poly(ethylene glycol) (PEG) and poly(L-aspartic acid) (PAsp) randomly grafted with pH-sensitive 2-(diisopropylamino)ethylamine (DIP) and diethylenetriamine (DETA) groups was synthesized via ring-opening polymerization and aminolysis reaction. Similar to polyethylenimine (PEI), the copolymer possesses a multiamine structure that not only allows effective siRNA complexation at neutral pH but also facilitates lysosomal release of siRNA via a proton buffering effect. Moreover, the poly(L-aspartic acid) backbone renders the vector biodegradability, which is not achievable with PEI. This novel polymeric vector can mediate effective intracellular siRNA delivery in various cancer cells. Consequently, the delivery of BCL-2 siRNA resulted in target gene silencing, inducing apoptosis and inhibiting the growth of cancer cells. These results show the potential of this non-PEI based polymeric vector with proton buffering capacity and biodegradability for siRNA delivery in cancer therapy.
authors: Yuanyuan
authors: Y
authors: Yuan
authors: Faming
authors: F
authors: Gong
authors: Yang
authors: Y
authors: Cao
authors: Weicai
authors: W
authors: Chen
authors: Du
authors: D
authors: Cheng
authors: Xintao
authors: X
authors: Shuai
mesh_terms: D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival; D011992:Endosomes / Q000378:metabolism; D005021:Ethylamines / Q000737:chemistry; D005434:Flow Cytometry; D020868:Gene Silencing; D005822:Genetic Vectors; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007834:Lasers; D008247:Lysosomes / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011522:Protons; D034741:RNA, Small Interfering / Q000737:chemistry*
chemical_list: C000601119:2-(diisoproylamino)ethylamine; D001672:Biocompatible Materials; D005021:Ethylamines; D010455:Peptides; D011108:Polymers; D011522:Protons; D034741:RNA, Small Interfering; C017645:polyaspartate; D011092:Polyethylene Glycols; D011094:Polyethyleneimine