Bioengineering fluorescent virus-like particle/RNAi nanocomplexes act synergistically with temozolomide to eradicate brain tumors

Hao Han Pang; Chiung Yin Huang; Ya Wen Chou; Chia Jung Lin; Zi Lin Zhou; Yow Ling Shiue; Kuo Chen Wei; Hung Wei Yang

doi:10.1039/c9nr01247h

Bioengineering fluorescent virus-like particle/RNAi nanocomplexes act synergistically with temozolomide to eradicate brain tumors

Hao Han Pang, Chiung Yin Huang, Ya Wen Chou, Chia Jung Lin, Zi Lin Zhou, Yow Ling Shiue, Kuo Chen Wei, Hung Wei Yang

Department of Biomedical Engineering

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

33 Citations (Scopus)

Abstract

The proof-of-concept strategy in this study based on biodegradable and biocompatible self-assembling fluorescent virus-like particle/RNAi nanocomplexes (VLP/RNAi) produced in Escherichia coli (E. coli) followed by surface modification with a cell-penetrating peptide (CPP) and an apolipoprotein E peptide (ApoEP) (dP@VLP/RNAi), which can cross the blood-brain barrier (BBB) to inhibit the DNA repair mechanism and act synergistically with temozolomide (TMZ) for promoting clinical chemotherapy has achieved good therapeutic effects towards malignant brain tumors. The synergistic value of this study's design was verified in intracranial mouse models of glioblastomas (GBMs). Intravenous administration of this formulation enhanced the curative efficacy of TMZ by downregulating the hepatocyte growth factor receptor (c-MET) gene in GBM U87 cells. Furthermore, upon gene-chemotherapy, the methylated DNA in GBM U87 cells was significantly enhanced by inhibiting the DNA repair mechanism, leading to significant brain tumor suppression. The results of this study could be critical for the design of RNAi-based genetic therapeutics for promoting chemotherapy against brain tumors.

Original language	English
Pages (from-to)	8102-8109
Number of pages	8
Journal	Nanoscale
Volume	11
Issue number	17
DOIs	https://doi.org/10.1039/c9nr01247h
Publication status	Published - 2019 May 7

All Science Journal Classification (ASJC) codes

General Materials Science

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title = "Bioengineering fluorescent virus-like particle/RNAi nanocomplexes act synergistically with temozolomide to eradicate brain tumors",

abstract = "The proof-of-concept strategy in this study based on biodegradable and biocompatible self-assembling fluorescent virus-like particle/RNAi nanocomplexes (VLP/RNAi) produced in Escherichia coli (E. coli) followed by surface modification with a cell-penetrating peptide (CPP) and an apolipoprotein E peptide (ApoEP) (dP@VLP/RNAi), which can cross the blood-brain barrier (BBB) to inhibit the DNA repair mechanism and act synergistically with temozolomide (TMZ) for promoting clinical chemotherapy has achieved good therapeutic effects towards malignant brain tumors. The synergistic value of this study's design was verified in intracranial mouse models of glioblastomas (GBMs). Intravenous administration of this formulation enhanced the curative efficacy of TMZ by downregulating the hepatocyte growth factor receptor (c-MET) gene in GBM U87 cells. Furthermore, upon gene-chemotherapy, the methylated DNA in GBM U87 cells was significantly enhanced by inhibiting the DNA repair mechanism, leading to significant brain tumor suppression. The results of this study could be critical for the design of RNAi-based genetic therapeutics for promoting chemotherapy against brain tumors.",

author = "Pang, {Hao Han} and Huang, {Chiung Yin} and Chou, {Ya Wen} and Lin, {Chia Jung} and Zhou, {Zi Lin} and Shiue, {Yow Ling} and Wei, {Kuo Chen} and Yang, {Hung Wei}",

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AU - Zhou, Zi Lin

AU - Shiue, Yow Ling

AU - Wei, Kuo Chen

AU - Yang, Hung Wei

PY - 2019/5/7

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Bioengineering fluorescent virus-like particle/RNAi nanocomplexes act synergistically with temozolomide to eradicate brain tumors

Abstract

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