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Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon

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 (...

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Autores principales: Li, Yan, Liu, Ruiyuan, Shi, Yuanjie, Zhang, Zhenzhong, Zhang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377727/
https://www.ncbi.nlm.nih.gov/pubmed/25825598
http://dx.doi.org/10.7150/thno.11234
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author Li, Yan
Liu, Ruiyuan
Shi, Yuanjie
Zhang, Zhenzhong
Zhang, Xin
author_facet Li, Yan
Liu, Ruiyuan
Shi, Yuanjie
Zhang, Zhenzhong
Zhang, Xin
author_sort Li, Yan
collection PubMed
description 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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spelling pubmed-43777272015-03-30 Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon Li, Yan Liu, Ruiyuan Shi, Yuanjie Zhang, Zhenzhong Zhang, Xin Theranostics Research Paper 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. Ivyspring International Publisher 2015-02-27 /pmc/articles/PMC4377727/ /pubmed/25825598 http://dx.doi.org/10.7150/thno.11234 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Li, Yan
Liu, Ruiyuan
Shi, Yuanjie
Zhang, Zhenzhong
Zhang, Xin
Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title_full Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title_fullStr Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title_full_unstemmed Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title_short Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon
title_sort zwitterionic poly(carboxybetaine)-based cationic liposomes for effective delivery of small interfering rna therapeutics without accelerated blood clearance phenomenon
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377727/
https://www.ncbi.nlm.nih.gov/pubmed/25825598
http://dx.doi.org/10.7150/thno.11234
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