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Binary System for MicroRNA-Targeted Imaging in Single Cells and Photothermal Cancer Therapy
Ruo-Can Qian1, Yue Cao1, Yi-Tao Long1
1Key Laboratory for Advanced Materials, School of Chemistry and Molecular Engineering, East China University of Science and Technology , 130 Meilong Road, Shanghai, 200237, People's Republic of China.
Abstract:
Abnormal expression of microRNAs (miRNAs) is often associated with tumorigenesis, metastasis, and progression. Among them, miRNA-21 is found to be overexpressed in most of the cancer cells. Here, a binary system is designed for miRNA-21 targeted imaging and photothermal treatment in single cells. The binary system is composed by a pair of probes (probe-1 and probe-2), which are encapsulated in liposomes for cell delivery. Both of the two probes adopt gold nanoparticles (AuNPs) as the core material, and the AuNPs are functionalized with Cy5-marked molecular beacon (MB-1/MB-2 for probe-1/probe-2, respectively). The loop part of MBs are designed to be complementary with miRNA-21. Therefore, after the binary system enters into the cytoplasm, MBs can be opened upon miRNA-21 triggered hybridization, which turns "on" the fluorescence of Cy5 for the localization of miRNA-21. At the same time, a cross-linking between the probes occurs since the far ends of MB-1 and MB-2 are designed to be complementary with each other. The miRNA-induced aggregation shifts the absorption of AuNPs to near-infrared, which can be observed under dark-field microscopy (DFM) and used for the following photothermal therapy. Under near-infrared (NIR) irradiation, MCF-7 breast cancer cells are successfully killed. The proposed system can be further applied in tumor-bearing mice and shows significant therapeutic effect. This work provides a new tool for intracellular miRNA analysis and targeted treatment against cancer.
Insights
This study introduces a novel binary system for detecting and treating cancers by targeting microRNA-21 (miRNA-21). The system enables precise imaging of cancer cells and effective photothermal therapy, demonstrating significant therapeutic effects in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Biology
Background:
- Aberrant microRNA (miRNA) expression is linked to cancer development and spread.
- miRNA-21 is frequently overexpressed in various cancer types, making it a potential therapeutic target.
Purpose of the Study:
- To design and evaluate a binary system for simultaneous imaging and photothermal therapy of miRNA-21 in cancer cells.
- To develop a tool for intracellular miRNA analysis and targeted cancer treatment.
Main Methods:
- A binary system using gold nanoparticles functionalized with molecular beacons (MBs) was developed for miRNA-21 detection.
- Liposomes encapsulated the probes for efficient cell delivery.
- miRNA-21 binding triggered Cy5 fluorescence for imaging and probe aggregation for photothermal therapy.
- Dark-field microscopy (DFM) was used for visualization, and near-infrared (NIR) irradiation induced cell death.
Main Results:
- The binary system successfully localized miRNA-21 within single cells by activating Cy5 fluorescence.
- miRNA-21 triggered probe aggregation, shifting gold nanoparticle absorption to the near-infrared spectrum.
- MCF-7 breast cancer cells were effectively killed upon NIR irradiation.
- The system showed significant therapeutic effects in tumor-bearing mice models.
Conclusions:
- The developed binary system offers a dual-function tool for intracellular miRNA analysis and targeted cancer photothermal therapy.
- This approach provides a promising new strategy for cancer treatment, particularly for cancers with elevated miRNA-21 levels.
