Research Project: RNA İlaç Taşıyabilen Spion Bazlı Çok Fonksiyonlu Nano taşıyıcıların Geliştirilmesi
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Contributors
Funders
ID
TB.00187
Authors
Acar, Havva Funda Yağcı
Faculty Member
Publications
Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles
(BioMed Central, 2020) Acar, Havva Funda Yağcı; Gözüaçık, Devrim; Ünal, Özlem; Akkoç, Yunus; Koçak, Muhammed; Nalbat, Esra; Doğan-Ekici, Asiye Işın; Department of Chemistry; Graduate School of Sciences and Engineering; KUTTAM (Koç University Research Center for Translational Medicine); KUYTAM (Koç University Surface Science and Technology Center); Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING; Research Center
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.
Magnetofection of green fluorescent protein encoding DNA-bearing polyethyleneimine-coated superparamagnetic iron oxide nanoparticles to human breast cancer cells
(American Chemical Society (ACS), 2019) Acar, Havva Funda Yağcı; Ünal, Özlem; Zuvin, Merve; Koşar, Ali; Gözüaçık, Devrim; Kutlu, Özlem; Kaya, Veysel Oğulcan; Kuruoğlu, Efe; Department of Chemistry; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Gene therapy is a developing method for the treatment of various diseases. For this purpose, the search for nonviral methods has recently accelerated to avoid toxic effects. A strong alternative method is magnetofection, which involves the use of superparamagnetic iron oxide nanoparticles (SPIONs) with a proper organic coating and external magnetic field to enhance the localization of SPIONs at the target site. In this study, a new magnetic actuation system consisting of four rare-earth magnets on a rotary table was designed and manufactured to obtain improved magnetofection. As a model, green fluorescent protein DNA-bearing polyethyleneimine-coated SPIONs were used. Magnetofection was tested on MCF7 cells. The system reduced the transfection time (down to 1 h) of the standard polyethyleneimine transfection protocol. As a result, we showed that the system could be effectively used for gene transfer.
