title: Zwitterionic poly(carboxybetaine)-based cationic liposomes for effective delivery of small interfering RNA therapeutics without accelerated blood clearance phenomenon.
abstract: For efficient delivery of small interfering RNA (siRNA) to the target diseased site in vivo, it is important to design suitable vehicles to control the blood circulation of siRNA. It has been shown that surface modification of cationic liposome/siRNA complexes (lipoplexes) with polyethylene glycol (PEG) could enhance the circulation time of lipoplexes. However, the first injection of PEGylated lipoplexes in vivo induces accelerated blood clearance and enhances hepatic accumulation of the following injected PEGylated lipoplexes, which is known as the accelerated blood clearance (ABC) phenomenon. Herein, we developed zwitterionic poly(carboxybetaine) (PCB) modified lipoplexes for the delivery of siRNA therapeutics, which could avoid protein adsorption and enhance the stability of lipoplexes as that for PEG. Quite different from the PEGylation, the PCBylated lipoplexes could avoid ABC phenomenon, which extended the blood circulation time and enhanced the tumor accumulation of lipoplexes in vivo. After accumulation in tumor site, the PCBylation could promote the cellular uptake and endosomal/lysosomal escape of lipoplexes due to its unique chemical structure and pH-sensitive ability. With excellent tumor accumulation, cellular uptake and endosomal/lysosomal escape abilities, the PCBylated lipoplexes significantly inhibited tumor growth and induced tumor cell apoptosis.
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China ; 3. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Ruiyuan
authors.initials: R
authors.lastname: Liu
authors.affiliation: 4. School of Life Sciences, University of Beijing Institute of Technology, Beijing, 100081, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 3. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1. National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D002412:Cations / Q000737:chemistry; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes / Q000097:blood / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000097:blood / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000178:Acrylamides; D002412:Cations; D008081:Liposomes; D011108:Polymers; D034741:RNA, Small Interfering; C533866:poly(carboxybetaine acrylamide); D011092:Polyethylene Glycols
keywords: Accelerated blood clearance (ABC) phenomenon.; Cationic liposomes; Poly(carboxybetaine); Polyethylene glycol; siRNA therapeutics
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