Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

2020-04-28
Unal, O
Akkoc, Y
Kocak, M
Nalbat, Esra
Dogan-Ekici, AI
Yagci, Acar
Gozuacik, D
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
178
views
0
downloads
Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.
SPION, Theranostic nanoparticle, Cancer treatment, Gene therapy, MicroRNA, MIR376B, Autophagy
https://hdl.handle.net/11511/31611
Journal of nanobiotechnology
Graduate School of Informatics, Article

Suggestions

The Antiproliferative Effect of Celecoxib Loaded pNIPAM Nanoparticles
Bayyurt, Banu; Hasırcı, Vasıf Nejat (2012-09-01)
The aim of this study was to design a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) nanoparticles (NPs). The model drug, Celecoxib, is a cyclooxygenase-2 inhibitor and has a great potential in chemoprevention and treatment of various cancer types, however, the clinical use is limited due to the side effects on the cardiovascular system which is most probably due to the high doses used in clinical applications. In this study, a novel nanoparticle preparation approach, nanoprecipitation, ...
Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery
ÜNSOY, GÖZDE; Khodadust, Rouhollah; Yalcin, Serap; Mutlu, Pelin; Gündüz, Ufuk (2014-10-01)
Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field. Among various materials, chitosan has a great importance as a pH sensitive...
Biopolymer based micro/nanoparticles as drug carriers for the treatment of skin diseases
Eke, Gözde; Hasırcı, Vasıf Nejat; Hasırcı, Nesrin; Department of Micro and Nanotechnology (2011)
Controlled drug delivery systems are becoming increasingly interesting with the contribution of nanotechnology. In the case of transdermal applications the greatest limitation is the highly impermeable outermost layer of the skin, the stratum corneum. One promising method of controlled transdermal drug delivery of the skin therapeutics is the use of nanoparticles as carriers. Encapsulation of the drug, as opposed to classical topical application of creams or emulsions, allows the drug to diffuse into hair f...
Superior Photodynamic Therapy of Colon Cancer Cells by Selenophene-BODIPY-Loaded Superparamagnetic Iron Oxide Nanoparticles
Ozvural Sertcelik, Kubra Nur; Karaman, Osman; Almammadov, Toghrul; Günbaş, Emrullah Görkem; Kolemen, Safacan; Yagci Acar, Havva; Onbasli, Kubra (2022-01-01)
© 2022 Wiley-VCH GmbH.Development of targeted nanoparticles as carriers to deliver photosensitizers to cancer cells is highly beneficial for ensuring the expected therapeutic outcome of photodynamic therapy. Herein, polyacrylic acid (PAA) coated superparamagnetic iron oxide nanoparticles (SPIONs), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) were loaded with a BODIPY-based (BOD-Se-I) photosensitizer (Cet-PAA@SPION/BOD-Se-I) to achieve enhanced and selective photodynami...
Targeted delivery of CPG-oligodeoxynucleotide to breast cancer cells by poly-amidoamine dendrimer-modified magnetic nanoparticles
Taghavi Pourianazar, Negar; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2016)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Citation Formats
O. Unal et al., “Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.,” Journal of nanobiotechnology, pp. 65–65, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31611.
METU IIS - Integrated Information Service open@metu.edu.tr