Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes

Mingji Jin,1 Guangming Jin,2 Lin Kang,1 Liqing Chen,1 Zhonggao Gao,1 Wei Huang11State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Diagnostic...

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Autores principales:	Jin M, Jin G, Kang L, Chen L, Gao Z, Huang W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PEG detachable co-delivery survivin siRNA paclitaxel pH responsive Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/43a5c19cd33845fe91abd0382a02d4ca
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spelling	oai:doaj.org-article:43a5c19cd33845fe91abd0382a02d4ca2021-12-02T02:17:36ZSmart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes1178-2013https://doaj.org/article/43a5c19cd33845fe91abd0382a02d4ca2018-04-01T00:00:00Zhttps://www.dovepress.com/smart-polymeric-nanoparticles-with-ph-responsive-and-peg-detachable-pr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mingji Jin,1 Guangming Jin,2 Lin Kang,1 Liqing Chen,1 Zhonggao Gao,1 Wei Huang11State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Diagnostic Radiology 2, Yanbian University Hospital, Yanji, Jilin, China Background: The co-delivery of chemotherapeutic agents and small interfering RNA (siRNA) within one cargo can enhance the anticancer outcomes through its synergistic therapeutic effects. Materials and methods: We prepared smart polymeric nanoparticles (NPs) with pH-responsive and poly(ethylene glycol) (PEG)-detachable properties to systemically co-deliver paclitaxel (PTX) and siRNA against survivin gene for lung cancer therapy. The cationic polyethyleneimine-block-polylactic acid (PEI-PLA) was first synthesized and characterized, with good biocompatibility. PTX was encapsulated into the hydrophobic core of the PEI-PLA polymers by dialysis, and then the survivin siRNA was loaded onto the PTX-loaded NPs (PEI-PLA/PTX) through electrostatic interaction between siRNA and PEI block. Finally, the negatively charged poly(ethylene glycol)-block-poly(l-aspartic acid sodium salt) (PEG-PAsp) was coated onto the surface of NPs by electrostatic interaction to form final smart polymeric NPs with mean particle size of 82.4 nm and zeta potential of 4.1 mV. After uptake of NPs by tumor cells, the PEG-PAsp segments became electrically neutral owing to the lower endosome pH and consequently detached from the smart NPs. This process allowed endosomal escape of the NPs through the proton-sponge effect of the exposed PEI moiety. Results: The resulting NPs achieved drug loading of 6.04 wt% and exhibited good dispersibility within 24 h in 10% fetal bovine serum (FBS). At pH 5.5, the NPs presented better drug release and cellular uptake than at pH 7.4. The NPs with survivin siRNA effectively knocked down the expression of survivin mRNA and protein owing to enhanced cell uptake of NPs. Cell counting kit-8 (CCK-8) assay showed that the NPs presented low systemic toxicity and improved antiproliferation effect of PTX on A549 cells. Moreover, in vivo studies demonstrated that accumulated NPs in the tumor site were capable of inhibiting the tumor growth and extending the survival rate of the mice by silencing the survivin gene and delivering PTX into tumor cells simultaneously. Conclusion: These results indicate that the prepared nano-vectors could be a promising co-delivery system for novel chemo/gene combination therapy. Keywords: PEG detachable, co-delivery, survivin siRNA, paclitaxel, pH responsive Jin MJin GKang LChen LGao ZHuang WDove Medical PressarticlePEG detachableco-deliverysurvivin siRNApaclitaxelpH responsiveMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2405-2426 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PEG detachable co-delivery survivin siRNA paclitaxel pH responsive Medicine (General) R5-920
spellingShingle	PEG detachable co-delivery survivin siRNA paclitaxel pH responsive Medicine (General) R5-920 Jin M Jin G Kang L Chen L Gao Z Huang W Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
description	Mingji Jin,1 Guangming Jin,2 Lin Kang,1 Liqing Chen,1 Zhonggao Gao,1 Wei Huang11State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2Department of Diagnostic Radiology 2, Yanbian University Hospital, Yanji, Jilin, China Background: The co-delivery of chemotherapeutic agents and small interfering RNA (siRNA) within one cargo can enhance the anticancer outcomes through its synergistic therapeutic effects. Materials and methods: We prepared smart polymeric nanoparticles (NPs) with pH-responsive and poly(ethylene glycol) (PEG)-detachable properties to systemically co-deliver paclitaxel (PTX) and siRNA against survivin gene for lung cancer therapy. The cationic polyethyleneimine-block-polylactic acid (PEI-PLA) was first synthesized and characterized, with good biocompatibility. PTX was encapsulated into the hydrophobic core of the PEI-PLA polymers by dialysis, and then the survivin siRNA was loaded onto the PTX-loaded NPs (PEI-PLA/PTX) through electrostatic interaction between siRNA and PEI block. Finally, the negatively charged poly(ethylene glycol)-block-poly(l-aspartic acid sodium salt) (PEG-PAsp) was coated onto the surface of NPs by electrostatic interaction to form final smart polymeric NPs with mean particle size of 82.4 nm and zeta potential of 4.1 mV. After uptake of NPs by tumor cells, the PEG-PAsp segments became electrically neutral owing to the lower endosome pH and consequently detached from the smart NPs. This process allowed endosomal escape of the NPs through the proton-sponge effect of the exposed PEI moiety. Results: The resulting NPs achieved drug loading of 6.04 wt% and exhibited good dispersibility within 24 h in 10% fetal bovine serum (FBS). At pH 5.5, the NPs presented better drug release and cellular uptake than at pH 7.4. The NPs with survivin siRNA effectively knocked down the expression of survivin mRNA and protein owing to enhanced cell uptake of NPs. Cell counting kit-8 (CCK-8) assay showed that the NPs presented low systemic toxicity and improved antiproliferation effect of PTX on A549 cells. Moreover, in vivo studies demonstrated that accumulated NPs in the tumor site were capable of inhibiting the tumor growth and extending the survival rate of the mice by silencing the survivin gene and delivering PTX into tumor cells simultaneously. Conclusion: These results indicate that the prepared nano-vectors could be a promising co-delivery system for novel chemo/gene combination therapy. Keywords: PEG detachable, co-delivery, survivin siRNA, paclitaxel, pH responsive
format	article
author	Jin M Jin G Kang L Chen L Gao Z Huang W
author_facet	Jin M Jin G Kang L Chen L Gao Z Huang W
author_sort	Jin M
title	Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
title_short	Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
title_full	Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
title_fullStr	Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
title_full_unstemmed	Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes
title_sort	smart polymeric nanoparticles with ph-responsive and peg-detachable properties for co-delivering paclitaxel and survivin sirna to enhance antitumor outcomes
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/43a5c19cd33845fe91abd0382a02d4ca
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Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes

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