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Biodegradable nanosyringes for intracellular amplification-based dual-diagnosis and gene therapy in single living cells† †Electronic supplementary information (ESI) available: Experimental details, additional data and graphs. See DOI: 10.1039/c9sc01894h

Authors :
Shen, Xiaotong
Zhang, Ying
Sun, Jianghui
Lu, Hua
Ouyang, Jin
Na, Na
Source :
Chemical Science
Publication Year :
2019
Publisher :
Royal Society of Chemistry, 2019.

Abstract

Biodegradable nanosyringes were prepared to achieve efficient loading, delivery and release of biomolecules (enzymes, nucleic acids, and even silencing RNA (siRNA)) into living cells for amplification-based dual-detection of cancer biomarkers and gene therapy for cancer.<br />The efficient delivery of biomolecules into living cells as well as their easy biodegradation have been challenges for the application of intracellular amplification for sensitive multiple-diagnosis and gene therapy for cancer. Herein, new strategies of amplification-based dual-detection of cancer biomarkers (Let-7a miRNA and VEGF) and gene therapy for cancers are put forward. These are achieved through biodegradable nanosyringes (NSs), rigid and sharp in vitro but degradable in vivo, which are applied for the efficient loading, delivery and release of biomolecules (enzymes, nucleic acids, and even silencing RNA) into living cells. After penetrating cell membranes and escaping from endosomes through their rigid and sharp tips, NSs release biomolecules for fast and easy “one-step” rolling circle amplification (ring formation and amplification) in single living cells. Therefore, based on signals from two probes, FAM-Probe and Cy5-Probe, that selectively bind to amplification products, 100 aM of Let-7a and 100 fM of VEGF could be detected, which are much lower than reported values. Furthermore, siRNAs can also be delivered by NSs for gene therapy, and their therapeutic effect was evaluated by their in vivo antitumor efficacy in CCRF-CEM subcutaneous xenograft nude mice. Rigid in vitro and degradable in vivo, NSs show potential for achieving fast, sensitive and safe cancer diagnosis and efficient therapy.

Subjects

Subjects :
Chemistry

Details

Language :
English
ISSN :
20416539 and 20416520
Volume :
10
Issue :
24
Database :
OpenAIRE
Journal :
Chemical Science
Accession number :
edsair.pmid..........c8a2a5c13a84721ef900dcfcf04ef8da