TY - JOUR
T1 - Probing the Role of Charged Functional Groups on Nanoparticles Grafted with Polyglycerol in Protein Adsorption and Cellular Uptake
AU - Zou, Yajuan
AU - Ito, Shinji
AU - Fujiwara, Masazumi
AU - Komatsu, Naoki
N1 - Funding Information:
The authors acknowledge Dr. Li Zhao (Soochow University), Prof. Hirohito Tsue, Dr. Toru Tsuchiya, Dr. Yuta Suzuki, and Dr. Takahiro Fujiwara (Kyoto University) for their helpful discussions. The authors also thank Mr. Haruyasu Kohda, Ms. Keiko Okamoto‐Furuta, and Mr. Tatsuya Katsuno (Kyoto University) for their help with TEM sample preparation, Dr. Junko Satoh (Kyoto University) for her help with LC‐MS/MS sample preparation. The analysis of FACS, TEM, and ICP was performed at the Analysis Center of Institute for Integrated Cell‐Material Sciences (iCeMS), Kyoto University with the help from Dr. Takayuki Homma and Dr. Masahiko Tsujimoto (iCeMS, Kyoto University). This work was supported in part by JSPS KAKENHI grant number 20H02584, 20H00335, and 21K19906 and by AMED grant number 211m0203013j0003. A part of the results was obtained by using research equipment shared in MEXT Project for promoting public utilization of advanced research infrastructure (program for supporting introduction of the new sharing system) grant number JPMXS0421700120. The TOC graphic was created with BioRender.com.
Funding Information:
The authors acknowledge Dr. Li Zhao (Soochow University), Prof. Hirohito Tsue, Dr. Toru Tsuchiya, Dr. Yuta Suzuki, and Dr. Takahiro Fujiwara (Kyoto University) for their helpful discussions. The authors also thank Mr. Haruyasu Kohda, Ms. Keiko Okamoto-Furuta, and Mr. Tatsuya Katsuno (Kyoto University) for their help with TEM sample preparation, Dr. Junko Satoh (Kyoto University) for her help with LC-MS/MS sample preparation. The analysis of FACS, TEM, and ICP was performed at the Analysis Center of Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University with the help from Dr. Takayuki Homma and Dr. Masahiko Tsujimoto (iCeMS, Kyoto University). This work was supported in part by JSPS KAKENHI grant number 20H02584, 20H00335, and 21K19906 and by AMED grant number 211m0203013j0003. A part of the results was obtained by using research equipment shared in MEXT Project for promoting public utilization of advanced research infrastructure (program for supporting introduction of the new sharing system) grant number JPMXS0421700120. The TOC graphic was created with BioRender.com. The 2.4 section subheading was corrected on May 25, 2022 after initial online publication.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/5/25
Y1 - 2022/5/25
N2 - In biofluids, charged functional groups on the surface of nanoparticles (NPs) interact with cells through the protein corona. However, the cascade effects of charged groups on corona formation and cellular uptake remain unclear. Herein, carboxy, sulfate, and amino groups are quantitatively introduced at the periphery of polyglycerol (PG)-grafted nanodiamond and superparamagnetic iron oxide NP to probe their roles in corona formation and cellular uptake. The uptake efficiency and intracellular aggregation state of NPs are revealed to correlate with protein affinity of the charged groups; sulfate at lower density and carboxylate exhibit no affinity to proteins, inducing negligible or no cellular uptake. In contrast, sulfate at higher density and ammonium associate with fetal bovine serum proteins to alter the aggregation state of the internalized NPs. It is further demonstrated that the distinct protein corona profiles on NP-PG-OSO3− and NP-PG-NH3+ surfaces dictate their uptake mechanism. The protein corona of NP-PG-OSO3− suppresses cellular uptake via downregulation of macropinocytosis and clathrin-mediated endocytosis, whereas that of NP-PG-NH3+ enhances uptake through upregulation of macropinocytosis and caveolae-mediated endocytosis. This study clarifies the elusive role of the charged groups in protein adsorption and cellular uptake, which sheds light on NP design for controlled cellular uptake and theranostics in nanomedicine.
AB - In biofluids, charged functional groups on the surface of nanoparticles (NPs) interact with cells through the protein corona. However, the cascade effects of charged groups on corona formation and cellular uptake remain unclear. Herein, carboxy, sulfate, and amino groups are quantitatively introduced at the periphery of polyglycerol (PG)-grafted nanodiamond and superparamagnetic iron oxide NP to probe their roles in corona formation and cellular uptake. The uptake efficiency and intracellular aggregation state of NPs are revealed to correlate with protein affinity of the charged groups; sulfate at lower density and carboxylate exhibit no affinity to proteins, inducing negligible or no cellular uptake. In contrast, sulfate at higher density and ammonium associate with fetal bovine serum proteins to alter the aggregation state of the internalized NPs. It is further demonstrated that the distinct protein corona profiles on NP-PG-OSO3− and NP-PG-NH3+ surfaces dictate their uptake mechanism. The protein corona of NP-PG-OSO3− suppresses cellular uptake via downregulation of macropinocytosis and clathrin-mediated endocytosis, whereas that of NP-PG-NH3+ enhances uptake through upregulation of macropinocytosis and caveolae-mediated endocytosis. This study clarifies the elusive role of the charged groups in protein adsorption and cellular uptake, which sheds light on NP design for controlled cellular uptake and theranostics in nanomedicine.
KW - cellular uptake
KW - charged functional groups
KW - nanoparticles
KW - polyglycerol
KW - protein corona
UR - http://www.scopus.com/inward/record.url?scp=85122727885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122727885&partnerID=8YFLogxK
U2 - 10.1002/adfm.202111077
DO - 10.1002/adfm.202111077
M3 - Article
AN - SCOPUS:85122727885
VL - 32
JO - Advanced Functional Materials
JF - Advanced Functional Materials
SN - 1616-301X
IS - 22
M1 - 2111077
ER -