A mannosylated PEI-CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy

Zhenzhen Pan; Xuejia Kang; Yuaner Zeng; Wenyuan Zhang; Huige Peng; Jinyu Wang; Wei Huang; Huiyuan Wang; Youqing Shen; Yongzhuo Huang

doi:10.1039/c7py00882a

A mannosylated PEI-CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy

Zhenzhen Pan, Xuejia Kang, Yuaner Zeng, Wenyuan Zhang, Huige Peng, Jinyu Wang, Wei Huang, Huiyuan Wang, Youqing Shen, Yongzhuo Huang

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Polyethylenimine (PEI) is the most widely applied polymeric vector in gene delivery. However, its therapeutic application is hampered by the high cytotoxicity and poor in vivo transfection efficiency. We constructed a mannosylated, bioreducible hybrid of low-molecular-weight PEI and cell-penetrating peptide (termed Man-PEI_5k-CPP) as a vector to deliver plasmid TRAIL (pTRAIL) for colorectal cancer treatment. We discovered that the colon cancer cells overexpressed mannose receptors (MR). With the combined functions of the tumor-targeting ligand and the CPP, the Man-PEI_5k-CPP not only increased the cellular uptake efficiency, but also improved the efficiency of transfection, thus yielding enhanced inhibition efficacy on HCT116 human colon cancer cells, compared to the conventional PEI_25k. The animal studies further confirmed the treatment success of Man-PEI_5k-CPP/pTRAIL in the mice bearing xenografted HCT116 tumors and showed minimal systemic toxicity.

Original language	English
Pages (from-to)	5275-5285
Number of pages	11
Journal	Polymer Chemistry
Volume	8
Issue number	35
DOIs	https://doi.org/10.1039/c7py00882a
State	Published - 21 Sep 2017
Externally published	Yes

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title = "A mannosylated PEI-CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy",

abstract = "Polyethylenimine (PEI) is the most widely applied polymeric vector in gene delivery. However, its therapeutic application is hampered by the high cytotoxicity and poor in vivo transfection efficiency. We constructed a mannosylated, bioreducible hybrid of low-molecular-weight PEI and cell-penetrating peptide (termed Man-PEI5k-CPP) as a vector to deliver plasmid TRAIL (pTRAIL) for colorectal cancer treatment. We discovered that the colon cancer cells overexpressed mannose receptors (MR). With the combined functions of the tumor-targeting ligand and the CPP, the Man-PEI5k-CPP not only increased the cellular uptake efficiency, but also improved the efficiency of transfection, thus yielding enhanced inhibition efficacy on HCT116 human colon cancer cells, compared to the conventional PEI25k. The animal studies further confirmed the treatment success of Man-PEI5k-CPP/pTRAIL in the mice bearing xenografted HCT116 tumors and showed minimal systemic toxicity.",

author = "Zhenzhen Pan and Xuejia Kang and Yuaner Zeng and Wenyuan Zhang and Huige Peng and Jinyu Wang and Wei Huang and Huiyuan Wang and Youqing Shen and Yongzhuo Huang",

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doi = "10.1039/c7py00882a",

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T1 - A mannosylated PEI-CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy

AU - Pan, Zhenzhen

AU - Kang, Xuejia

AU - Zeng, Yuaner

AU - Zhang, Wenyuan

AU - Peng, Huige

AU - Wang, Jinyu

AU - Huang, Wei

AU - Wang, Huiyuan

AU - Shen, Youqing

AU - Huang, Yongzhuo

PY - 2017/9/21

Y1 - 2017/9/21

N2 - Polyethylenimine (PEI) is the most widely applied polymeric vector in gene delivery. However, its therapeutic application is hampered by the high cytotoxicity and poor in vivo transfection efficiency. We constructed a mannosylated, bioreducible hybrid of low-molecular-weight PEI and cell-penetrating peptide (termed Man-PEI5k-CPP) as a vector to deliver plasmid TRAIL (pTRAIL) for colorectal cancer treatment. We discovered that the colon cancer cells overexpressed mannose receptors (MR). With the combined functions of the tumor-targeting ligand and the CPP, the Man-PEI5k-CPP not only increased the cellular uptake efficiency, but also improved the efficiency of transfection, thus yielding enhanced inhibition efficacy on HCT116 human colon cancer cells, compared to the conventional PEI25k. The animal studies further confirmed the treatment success of Man-PEI5k-CPP/pTRAIL in the mice bearing xenografted HCT116 tumors and showed minimal systemic toxicity.

AB - Polyethylenimine (PEI) is the most widely applied polymeric vector in gene delivery. However, its therapeutic application is hampered by the high cytotoxicity and poor in vivo transfection efficiency. We constructed a mannosylated, bioreducible hybrid of low-molecular-weight PEI and cell-penetrating peptide (termed Man-PEI5k-CPP) as a vector to deliver plasmid TRAIL (pTRAIL) for colorectal cancer treatment. We discovered that the colon cancer cells overexpressed mannose receptors (MR). With the combined functions of the tumor-targeting ligand and the CPP, the Man-PEI5k-CPP not only increased the cellular uptake efficiency, but also improved the efficiency of transfection, thus yielding enhanced inhibition efficacy on HCT116 human colon cancer cells, compared to the conventional PEI25k. The animal studies further confirmed the treatment success of Man-PEI5k-CPP/pTRAIL in the mice bearing xenografted HCT116 tumors and showed minimal systemic toxicity.

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U2 - 10.1039/c7py00882a

DO - 10.1039/c7py00882a

M3 - 文章

AN - SCOPUS:85029405664

SN - 1759-9954

VL - 8

SP - 5275

EP - 5285

JO - Polymer Chemistry

JF - Polymer Chemistry

IS - 35

ER -

A mannosylated PEI-CPP hybrid for TRAIL gene targeting delivery for colorectal cancer therapy

Abstract

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