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PH-responsive hybrid nanoparticle with enhanced dissociation characteristic for siRNA delivery.


ABSTRACT:

Introduction

Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application.

Materials and methods

In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes.

Results

The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity.

Conclusion

Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.

SUBMITTER: Shi M 

PROVIDER: S-EPMC6207255 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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pH-responsive hybrid nanoparticle with enhanced dissociation characteristic for siRNA delivery.

Shi Menghao M   Zhao Xiufeng X   Zhang Jiulong J   Pan Shuang S   Yang Chunrong C   Wei Ying Y   Hu Haiyang H   Qiao Mingxi M   Chen Dawei D   Zhao Xiuli X  

International journal of nanomedicine 20181026


<h4>Introduction</h4>Specific polo-like kinase (PLK1) silencing with small interface RNA (siRNA) may be an effective approach for PLK1-overexpressed lung cancer. However, low siRNA concentration into cytoplasm of tumor tissue severely limits its application.<h4>Materials and methods</h4>In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with  ...[more]

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