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Background: MicroRNAs (miRNAs) are emerging as vital biomarkers since their abnormal expression is associated with various disease types including cancer. Therefore, it is essential to develop a sensitive and specific platform to monitor the dynamic expression of miRNAs for early clinical diagnosis and treatment. In this study, we designed a functionalized polydopamine (PDA)-based theranostic nanoprobe for efficient detection of miR-21 and in vivo synergistic cancer therapy.
Methods: PDA was synthesized from dopamine hydrochloride and functionalized with polyethylene glycol (PEG). PDA-PEG nanoparticles were loaded with FITC-labeled hairpin DNA (hpDNA) and an anticancer drug doxorubicin (DOX). The measurement of miRNA-21 expression was reflected by the fluorescence quenching and release assay. The cellular toxicity of nanoprobe was assessed by Cell Counting Kit-8 (CCK-8) assay. Furthermore, the diagnosis and therapy effect of nanoparobe were investigated in xenograft tumor models.
Results: PDA-PEG nanoparticles showed good stability in different solutions and effectively quench the fluorescence of FITC-labeled hpDNA. The presence of miR-21 induced the dissociation of hpDNA from PDA-PEG and subsequent the recovery of fluorescence signals. Upon cellular uptake of these nanoprobes, a dose-dependent fluorescence activation and synergetic cytotoxic effect were observed due to the release of DOX and inhibition of miR-21 function. Furthermore, PDA-PEG-DOX-hpDNA nanoparticles can afford long-term monitoring of miR-21 and combined therapeutic efficacy in the nude mice bearing 4T1 tumors.
Conclusions: Our results demonstrate the capability of PDA-PEG-DOX-hpDNA as a theranostic nanoprobe for continuously tracking of miRNAs and synergetic cancer therapy.
Keywords
PDA nanoparticles, miRNA-21, Imaging, Cancer theranostics
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This is a preprint. It has not completed peer review.
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Molecular Therapy - Nucleic Acids.
Version 1
Posted 22 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Molecular Therapy - Nucleic Acids.
Background: MicroRNAs (miRNAs) are emerging as vital biomarkers since their abnormal expression is associated with various disease types including cancer. Therefore, it is essential to develop a sensitive and specific platform to monitor the dynamic expression of miRNAs for early clinical diagnosis and treatment. In this study, we designed a functionalized polydopamine (PDA)-based theranostic nanoprobe for efficient detection of miR-21 and in vivo synergistic cancer therapy.
Methods: PDA was synthesized from dopamine hydrochloride and functionalized with polyethylene glycol (PEG). PDA-PEG nanoparticles were loaded with FITC-labeled hairpin DNA (hpDNA) and an anticancer drug doxorubicin (DOX). The measurement of miRNA-21 expression was reflected by the fluorescence quenching and release assay. The cellular toxicity of nanoprobe was assessed by Cell Counting Kit-8 (CCK-8) assay. Furthermore, the diagnosis and therapy effect of nanoparobe were investigated in xenograft tumor models.
Results: PDA-PEG nanoparticles showed good stability in different solutions and effectively quench the fluorescence of FITC-labeled hpDNA. The presence of miR-21 induced the dissociation of hpDNA from PDA-PEG and subsequent the recovery of fluorescence signals. Upon cellular uptake of these nanoprobes, a dose-dependent fluorescence activation and synergetic cytotoxic effect were observed due to the release of DOX and inhibition of miR-21 function. Furthermore, PDA-PEG-DOX-hpDNA nanoparticles can afford long-term monitoring of miR-21 and combined therapeutic efficacy in the nude mice bearing 4T1 tumors.
Conclusions: Our results demonstrate the capability of PDA-PEG-DOX-hpDNA as a theranostic nanoprobe for continuously tracking of miRNAs and synergetic cancer therapy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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