Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition

Autor:	Takuya Nishinakagawa, Mai Hazekawa, Takahiro Uchida, Daisuke Ishibashi, Takeshi Mori, Miyako Yoshida
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Small interfering RNA Science Cell macromolecular substances Gene delivery Endocytosis Micelle Article Cell membrane chemistry.chemical_compound Immunoglobulin Fab Fragments Mice Polylactic Acid-Polyglycolic Acid Copolymer Cell Line Tumor Neoplasms medicine Animals Humans Cyclin B1 RNA Small Interfering Micelles RNA Double-Stranded Multidisciplinary Chemistry Pharmaceutics Gene Transfer Techniques technology industry and agriculture PLGA medicine.anatomical_structure Cell culture Drug delivery Biophysics Heterografts Medicine
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that protects siRNAs from nucleases and facilitates siRNA cellular uptake is required. We previously reported the potential of siRNA-poly(D,L-lactic-co-glycolic acid; PLGA) micelles as an effective siRNA delivery tool in a murine peritoneal dissemination model by local injection. However, there was no effective formulation for siRNA delivery to target cells via intravenous injection. This study aimed to prepare siRNA–PLGA/Fabʹ–PLGA mixed micelles for siRNA delivery to target floating cells and evaluate its formulation in vitro. As the target siRNA protein in CEMx174, CyclinB1 levels were significantly reduced when siRNA–PLGA/Fabʹ–PLGA mixed micelles were added to cells compared with siRNA–PLGA micelles. siRNA–PLGA/Fabʹ–PLGA mixed micelles have high cell permeability and high target cell accumulation by endocytosis because flow cytometry detected labeling micelles in target cells. This study supports siRNA–PLGA/Fabʹ–PLGA mixed micelles as an effective siRNA delivery tool. This formulation can be administered systemically in dosage form against target cells, including cancer metastasis or blood cancer.
Databáze:	OpenAIRE
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