Effect of Protein Corona on Mitochondrial Targeting Ability and Cytotoxicity of Triphenylphosphonium Conjugated with Polyglycerol-Functionalized Nanodiamond
Autor: | Naoki Komatsu, Heon Gyu Kang, Yajuan Zou, Wei Wang, Yuquan Wang, Guoqing Cheng, Nishikawa Masahiro |
---|---|
Rok vydání: | 2021 |
Předmět: |
Glycerol
endocrine system Endosome Polymers Pharmaceutical Science Protein Corona 02 engineering and technology 030226 pharmacology & pharmacy Nanodiamonds Polyethylene Glycols HeLa 03 medical and health sciences 0302 clinical medicine Organophosphorus Compounds Lysosome Neoplasms Drug Discovery medicine Moiety Humans Cytotoxicity Cell Proliferation Drug Carriers biology Chemistry 021001 nanoscience & nanotechnology biology.organism_classification Mitochondria medicine.anatomical_structure A549 Cells Biophysics Molecular Medicine Surface modification 0210 nano-technology Fetal bovine serum HeLa Cells |
Zdroj: | Molecular pharmaceutics. 18(7) |
ISSN: | 1543-8392 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |