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We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.


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Aggregation-induced emission (AIE) dye loaded polymer nanoparticles for gene silencing in pancreatic cancer and their in vitro and in vivo biocompatibility evaluation

Show Author's information Rui Hu1Chengbin Yang1Yucheng Wang1Guimiao Lin2Wei Qin3Qingling Ouyan1Wing-Cheung Law4Quoc Toan Nguyen5Ho Sup Yoon5Xiaomei Wang2Ken-Tye Yong1( )Ben Zhong Tang3( )
School of Electrical and Electronic EngineeringNanyang Technological UniversitySingapore639798Singapore
The Engineering Lab of Synthetic Biology and the Key Lab of Biomedical EngineeringSchool of MedicineShenzhen UniversityShenzhen518060China
Department of ChemistryThe Hong Kong University of Science and TechnologyClear Water Bay, Kowloon, Hong KongChina
Department of Industrial and Systems EngineeringThe Hong Kong Polytechnic UniversityHung Hom, Kowloon, Hong KongP.R. China
Division of Structural Biology & BiochemistrySchool of Biological SciencesNanyang Technological UniversitySingapore639798Singapore

Abstract

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

Keywords: aggregation-induced emission, pancreatic cancer, gene silencing, polymer nanoparticles

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Publication history
Copyright
Acknowledgements

Publication history

Received: 14 August 2014
Revised: 08 November 2014
Accepted: 14 November 2014
Published: 06 December 2014
Issue date: May 2015

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Acknowledgements

Acknowledgement

This work was supported by the National Natural Science Foundation of China (NSFC) (61107017, 81301318), the Start-up grant (M4080141.040) from Nanyang Technological University, Tier 1 Academic Research Funds (M4010360.040 RG29/10) from Singapore Ministry of Education and partially from the Singapore Ministry of Education under a Tier 2 Research Grant MOE2010-T2-2-010 (4020020.040 ARC2/11) and the grant from the Shenzhen Basic Research Project (JC201005280391A)

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