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    Magnetic Gelatin Nanoparticles As A Biocompatible Carrier System for Small Interfering RNA in Human Colorectal Cancer: Synthesis, Optimization, Characterization, and Cell Viability Studies
    (2022) Selimovic, Amina; Kara, Goknur; Denkbas, Emir Baki
    Iron oxide-based nanoparticles have gained tremendous attention in developing next-generation personalized medicine modalities. Gelatin can be a good alternative for encapsulating iron oxide nanoparticles with its biocompatibility, biodegradability, low immunogenicity, and richness of functional groups. Herein, magnetic iron oxide nanoparticles (MNPs) were synthesized, coated with gelatin (Gel-MNPs), and loaded with mammalian target of rapamycin (mTOR)-silencing siRNA to induce the in vitro therapeutic effect in colorectal cancer (CRC) cells. To the best of our knowledge, this study is the first report using Gel-MNPs as siRNA carriers. We first optimized several experimental conditions for the preparation of MNPs and Gel-MNPs and the resulting opti-mized nanoparticles showed a narrow size and size distribution. Gelatin-coating increased the storage stability by preventing the aggregation of MNPs and did not alter the magnetic characteristics of MNPs significantly. siRNA encapsulation abilities of Gel-MNPs were determined in the range of 18.4% and 41.5% in varying siRNA amounts. Bare Gel-MNPs were highly cytocompatible against CRC cells, Caco-2, while Gel-MNPs-mTOR-siRNA exhibited a significant anticancer effect to kill these cells. Comparison with HiPerFect, a commercial siRNA transfection reagent, demonstrated that Gel-MNPs-mTOR-siRNA inhibited cell viability almost similar to or better than HiPerFect-mTOR-siRNA. Taken together, our data indicated that Gel-MNPs could potentially be used in further gene silencing approaches as a safe and multifunctional siRNA carrier candidate.
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    Silencing of survivin and cyclin B1 through siRNA-loaded arginine modified calcium phosphate nanoparticles for non-small-cell lung cancer therapy
    (2020) Kara, Goknur; Parlar, Ayhan; Cakmak, Melike Cokol; Coko, Murat; Denkbas, Emir Baki; Bakan, Feray; 32956996
    With the development of nanotechnology, various drug delivery systems including inorganic nanoparticles, liposomes, polymers, etc. have been developed over the past decade. Some of these nanoparticles are also forthcoming candidates for the successful delivery of small interfering RNA (siRNA) for targeted gene silencing. Upon its discovery, siRNA was perceived as a highly promising agent in the treatment of various diseases. However, it could not exhibit the expected clinical outcomes owing to the unfavorable challenges during delivery. One such challenge was identified as the lack of an effective carrier. Among the carriers, calcium phosphate (CaP) nanoparticles have attracted remarkable attention due to the superior biochemical properties and hold great promise for siRNA. It is well known that synthesis conditions influence the types of crystalline phases of CaPs as well as morphology. In this study, to address the influence of these parameters on the success of siRNA delivery, three different arginine (Arg) modified CaP nanoparticles having different chemical and morphological characteristics were synthesized as being the carriers of two specific siRNAs against survivin and cyclin B1. The functioning of CaP surfaces with Arg results in positive zeta potential on the surfaces. Functionalized nanoparticles have a higher loading capacity compared to unmodified particles, as they have a cationic surface that can be easily attached to negatively charged siRNAs. The gene silencing ability and the consequent in vitro antitumor activity of these CaP-Arg-siRNA complexes were investigated using A549 non-small-cell lung cancer cells. We found that high survivin and cyclin B1 expression is associated with worse survival in patients with lung cancer based on the Kaplan-Meier database. Considering the promoting role of survivin and cyclin B1 in cancer development and progression, CaP-Arg-siRNA mediated suppression of these genes resulted in a significant decrease in cell growth and induction of apoptosis. Our data suggest that all three CaP-Arg nanoparticles synthesized in this work can be used as safe and efficient nanocarriers for siRNA delivery, offering the opportunity to develop new therapeutic strategies for the treatment of lung cancer.