期刊
THERANOSTICS
卷 5, 期 6, 页码 583-596出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.11234
关键词
Cationic liposomes; siRNA therapeutics; Poly(carboxybetaine); Polyethylene glycol; Accelerated blood clearance (ABC) phenomenon
资金
- National Natural Science Foundation of China [21304099, 51203162, 51103159, 51373177]
- National High Technology Research and Development Program [2014AA020708, 2012AA022703, 2012AA020804]
- Instrument Developing Project of the Chinese Academy of Sciences [YZ201253, YZ201313]
- Open Funding Project of the National Key Laboratory of Biochemical Engineering [Y22504A169]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA09030301-3]
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.
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