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Cancer Cell Theranostics based on MicroRNA/Bi2Se3 Nanoparticle Complex

초록/요약

Cancer cell theranostic agents as the newly-emerged therapeutic tools, are usually composed of a nanoplatform and therapeutic/imaging functionaries. An ideal nanoplatform should possess a: (i) proper size; (ii) good biocompatibility, hydrophobicity and surface functionalizability; (iii) capability of imaging, cargo delivery and tracking; (iv) ability to perform therapeutic tasks. Recently, bismuth selenide nanoparticle (Bi2Se3 NP) as a class of topological insulator (TI) has shown exotic electrochemical and plasmonic features to be a potential nanoplatform candidate. On the other hand, microRNA (miRNA) has represented significant capability of cancer diagnosis and therapy to be perfectly applied in theranostics. However, precise detection of miRNAs due to their homologous sequences and low abundance in living cells is still challenging. Also, direct utilization of Bi2Se3 NPs into the biotechnological applications is still restricted due to the surface functionalization, hydrophobicity and biocompatibility issues. In this study, we firstly could accurately detect miRNA and confirmed its function as a notable cancer biomarker, by profiling two cancer cell subtypes based on their difference in miRNA expression levels. Then, we synthesized Bi2Se3 NP and enhanced its surface functionalizability and water solubility by its encapsulation with Au and Ag to fabricate plasmonic biocompatible nanocarriers. A newly-developed multifunctional SERS-active PTT nanoparticle composed of Au@Bi2Se3 core shell nanoparticle harboring anti-miRNA and folic acid mediated pH-sensitive cell penetrating peptide was reported to selectively treat cancer cells by employing both miRNA detection/inhibition and photothermal therapy. Also, by encapsulation of Bi2Se3 with Ag and designing a novel three-way junction RNA structure, for the first time we could address the nanoparticle multi-functionalization challenges and report a new paradigm for prerequisite drug delivery and miRNA inhibition mechanism to give rise to a highly efficient cancer cell differentiation therapy. The proposed study sheds the light on the significance of miRNA as a diagnosis and therapeutic functionary as well as the biotechnological applications of exotic Bi2Se3 nanoparticle to pave the way for the fabrication of more practical and reliable theranostic agents.

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