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Effect of Protein Corona on Mitochondrial Targeting Ability and Cytotoxicity of Triphenylphosphonium Conjugated with Polyglycerol-Functionalized Nanodiamond.
Zou, Yajuan; Nishikawa, Masahiro; Kang, Heon Gyu; Cheng, Guoqing; Wang, Wei; Wang, Yuquan; Komatsu, Naoki.
Afiliación
  • Zou Y; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • Nishikawa M; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • Kang HG; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • Cheng G; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • Wang W; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • Wang Y; Key Laboratory for Physical Electronics and Devices of the Ministry of Education and Key Laboratory of Photonics Technology for Information of Shaanxi Province, School of Electronics Science and Engineering, Xi'an Jiaotong University, Xi'an 710049, China.
  • Komatsu N; Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Mol Pharm ; 18(7): 2823-2832, 2021 07 05.
Article en En | MEDLINE | ID: mdl-34165304
Functionalization of nanoparticles (NPs) with targeting moieties has a high potential to advance precision nanomedicine. However, the targeting moieties on a NP surface are known to be masked by a protein corona in biofluids, lowering the targeting efficiency. Although it has been demonstrated at the cellular level, little is known about the influence of the protein corona on the subcellular targeting. Herein, we adopted triphenylphosphonium (TPP) as a mitochondrial targeting moiety and investigated the effects of protein coronas from fetal bovine serum and human plasma on its targeting ability and cytotoxicity. Specifically, we introduced TPP in low (l) and high (h) densities on the surface of nanodiamond (ND) functionalized with polyglycerol (PG). Despite the "corona-free" PG interface, we found that the TPP moiety attracted proteins to form a corona layer with clear linearity between the TPP density and the protein amount. By performing investigations on human cervix epithelium (HeLa) and human lung epithelial carcinoma (A549) cells, we further demonstrated that (1) the protein corona alleviated the cytotoxicity of both ND-PG-TPP-l and -h, (2) a smaller amount of proteins on the surface of ND-PG-TPP-l did not affect its mitochondrial targeting ability, and (3) a larger amount of proteins on the surface of ND-PG-TPP-h diminished its targeting specificity by restricting the NDs inside the endosome and lysosome compartments. Our findings will provide in-depth insights into the design of NPs with active targeting moiety for more precise and safer delivery at the subcellular level.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organofosforados / Polietilenglicoles / Polímeros / Nanodiamantes / Corona de Proteínas / Glicerol / Mitocondrias / Neoplasias Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organofosforados / Polietilenglicoles / Polímeros / Nanodiamantes / Corona de Proteínas / Glicerol / Mitocondrias / Neoplasias Límite: Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos