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In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy
Do Won Hwang1, Han Young Kim2, Fangyuan Li3
1Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Medical Research Center, Institute of Radiation Medicine, Seoul National University College of Medicine, Republic of Korea; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract:
Oncogene-targeted nucleic acid therapy has been spotlighted as a new paradigm for cancer therapeutics. However, in vivo delivery issues and uncertainty of therapeutic antisense drug reactions remain critical hurdles for a successful targeted cancer therapy. In this study, we developed a fluorescence-switchable theranostic nanoplatform using hyaluronic acid (HA)-conjugated graphene oxide (GO), which is capable of both sensing oncogenic miR-21 and inhibiting its tumorigenicity simultaneously. Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes loaded onto HA-GO (HGP21) specifically targeted CD44-positive MBA-MB231 cells and showed fluorescence recovery by interacting with endogenous miR-21 in the cytoplasm of the MBA-MB231 cells. Knockdown of endogenous miR-21 by HGP21 led to decreased proliferation and reduced migration of cancer cells, as well as the induction of apoptosis, with enhanced PTEN levels. Interestingly, in vivo fluorescence signals markedly recovered 3 h after the intravenous delivery of HGP21 and displayed signals more than 5-fold higher than those observed in the HGPscr-treated group of tumor-bearing mice. These findings demonstrate the possibility of using the HGP nanoplatform as a cancer theranostic tool in miRNA-targeted therapy.
Insights
A novel nanoplatform using hyaluronic acid-conjugated graphene oxide simultaneously detects and inhibits oncogenic miR-21 in cancer cells. This theranostic tool shows promise for targeted cancer therapy by improving in vivo delivery and therapeutic outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- Oncogene-targeted nucleic acid therapy offers a new approach for cancer treatment.
- Challenges in in vivo delivery and unpredictable drug reactions hinder targeted cancer therapy.
- MicroRNA-21 (miR-21) is an oncogene frequently overexpressed in various cancers.
Purpose of the Study:
- To develop a fluorescence-switchable theranostic nanoplatform for simultaneous sensing and inhibition of oncogenic miR-21.
- To evaluate the efficacy of the nanoplatform in targeting CD44-positive cancer cells and inhibiting tumor growth.
- To assess the in vivo performance and theranostic capabilities of the developed nanoplatform.
Main Methods:
- Conjugation of hyaluronic acid (HA) with graphene oxide (GO) and loading of Cy3-labeled antisense miR-21 peptide nucleic acid (PNA) probes (HGP21).
- Specific targeting of CD44-positive MBA-MB231 cells and in vitro evaluation of miR-21 sensing and inhibition.
- In vivo intravenous administration of HGP21 in tumor-bearing mice and monitoring of fluorescence signals and therapeutic effects.
Main Results:
- HGP21 specifically targeted CD44-positive cancer cells, with fluorescence recovery indicating interaction with endogenous miR-21.
- Knockdown of miR-21 by HGP21 significantly reduced cancer cell proliferation and migration, and induced apoptosis, with increased PTEN levels.
- In vivo studies showed marked fluorescence signal recovery within 3 hours post-intravenous delivery, with signals over 5-fold higher than controls in tumor-bearing mice.
Conclusions:
- The developed HA-conjugated GO nanoplatform (HGP21) functions as an effective theranostic tool for miRNA-targeted cancer therapy.
- This nanoplatform enables simultaneous sensing and inhibition of oncogenic miR-21, overcoming key delivery hurdles.
- The findings highlight the potential of this nanoplatform for advanced cancer diagnostics and therapeutics.
