Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy

Yujing Li; Jianxun Ding; Xiaoding Xu; Run Shi; Phei Er Saw; Junqing Wang; Shirley Chung; Wenliang Li; Bader M. Aljaeid; Robert J. Lee; Wei Tao; Lesheng Teng; Omid C. Farokhzad; Jinjun Shi

doi:10.1021/acs.nanolett.0c00757

Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy

Yujing Li, Jianxun Ding, Xiaoding Xu, Run Shi, Phei Er Saw, Junqing Wang, Shirley Chung, Wenliang Li, Bader M. Aljaeid, Robert J. Lee, Wei Tao, Lesheng Teng^*, Omid C. Farokhzad^*, Jinjun Shi^*

^*Corresponding author for this work

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

52 Citations (Scopus)

Abstract

As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.

Original language	English
Pages (from-to)	4857-4863
Number of pages	7
Journal	Nano Letters
Volume	20
Issue number	7
DOIs	https://doi.org/10.1021/acs.nanolett.0c00757
Publication status	Published - 8 Jul 2020
Externally published	Yes

Keywords

CDC20
RNA interference
cancer therapy
gene silencing
hypoxia
polypeptide nanoparticle

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.nanolett.0c00757

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title = "Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy",

abstract = "As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.",

keywords = "CDC20, RNA interference, cancer therapy, gene silencing, hypoxia, polypeptide nanoparticle",

author = "Yujing Li and Jianxun Ding and Xiaoding Xu and Run Shi and Saw, {Phei Er} and Junqing Wang and Shirley Chung and Wenliang Li and Aljaeid, {Bader M.} and Lee, {Robert J.} and Wei Tao and Lesheng Teng and Farokhzad, {Omid C.} and Jinjun Shi",

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year = "2020",

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doi = "10.1021/acs.nanolett.0c00757",

language = "English",

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T1 - Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy

AU - Li, Yujing

AU - Ding, Jianxun

AU - Xu, Xiaoding

AU - Shi, Run

AU - Saw, Phei Er

AU - Wang, Junqing

AU - Chung, Shirley

AU - Li, Wenliang

AU - Aljaeid, Bader M.

AU - Lee, Robert J.

AU - Tao, Wei

AU - Teng, Lesheng

AU - Farokhzad, Omid C.

AU - Shi, Jinjun

PY - 2020/7/8

Y1 - 2020/7/8

N2 - As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.

AB - As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of CDC20 and exhibited potent antitumor efficacy. We expect that this strategy of targeting hypoxia-correlated protumorigenic genes by hypoxia-responsive RNAi nanoparticles may provide a promising approach in cancer therapy.

KW - CDC20

KW - RNA interference

KW - cancer therapy

KW - gene silencing

KW - hypoxia

KW - polypeptide nanoparticle

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DO - 10.1021/acs.nanolett.0c00757

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EP - 4863

JO - Nano Letters

JF - Nano Letters

IS - 7

ER -

Dual Hypoxia-Targeting RNAi Nanomedicine for Precision Cancer Therapy

Abstract

Keywords

UN SDGs

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