TY - JOUR
T1 - Increasing the Efficacy of Gold Nanorod Uptake in Stem Cell-Derived Therapeutic Cells
T2 - Implications for Stem Cell Labeling and Optical Coherence Tomography Imaging
AU - Marquart, Grant W.
AU - Stoddard, Jonathan
AU - Kinnison, Karen
AU - Zhou, Felicia
AU - Hugo, Richard
AU - Ryals, Renee
AU - Shubert, Scott
AU - McGill, Trevor J.
AU - Mackiewicz, Marilyn R.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) grant # RL5GM118963, UL1GM118964, and TL4GM118965 and by the National Science Foundation grant # 2145427. It was also supported by the Integrated Pathology Core at the Oregon National Primate Research Center (ONPRC), which is supported by the NIH Award P51 OD 011092. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Authors G.W.M., K.K., R.H., and F.Z. received support from # RL5GM118963, UL1GM118964, and TL4GM118965. J.S., R.R., S.S., and T.M. received support for the project through the Integrated Pathology Core at the Oregon National Primate Research Center (ONPRC), which is supported by the NIH Award P51 OD 011092. M.R.M., received support from NIH grants # RL5GM118963, UL1GM118964, and TL4GM118965 and the National Science Foundation grant # 2145427.
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/5/27
Y1 - 2022/5/27
N2 - The advancement of safe nanomaterials for use as optical coherence tomography (OCT) imaging and stem cell-labeling agents to longitudinally visually track therapeutic derived retinal stem cells to study their migration, survival rate, and efficacy is challenged by instability, intracellular aggregation, low uptake, and cytotoxicity. Here, we describe a series of hybrid lipid-coated gold nanorods (AuNRs) that could solve these issues. These nanomaterials were made via a layer-by-layer assembly approach, and their stability in biological media, mechanism, efficiency of uptake, and toxicity were compared with a commercially available set of AuNRs with a 5 nm mesoporous silica (mSiO2)-polymer coating. These nanomaterials can serve as stem cell labeling and OCT imaging agents because they absorb in the near-infrared (NIR) region away from biological tissues. Although both subtypes of AuNRs were taken up by retinal pigment epithelial, neural progenitor, and baby hamster kidney cells, slightly negatively charged hybrid lipid-coated AuNRs had minimal aggregation in biological media and within the cytoplasm of cells (∼3000 AuNRs/cell) as well as minimal impact on cell health. Hybrid lipid-coated AuNRs modified with cell-penetrating peptides had the least toxicological impact, with >92% cell viability. In contrast, the more "sticky" AuNRs with a 5 nm mSiO2-polymer coating showed significant aggregation in biological media and within the cytoplasm with lower-than-expected uptake of AuNRs (∼5400 of AuNRs/cell) given their highly positive surface charge (35+ mV). Collectively, we have demonstrated that hybrid lipid-coated AuNRs, which absorb in the NIR-II region away from biological tissues, with tuned surface chemistry can label therapeutic derived stem cells with minimal aggregation and impact on cell health as well as enhance uptake for OCT imaging applications.
AB - The advancement of safe nanomaterials for use as optical coherence tomography (OCT) imaging and stem cell-labeling agents to longitudinally visually track therapeutic derived retinal stem cells to study their migration, survival rate, and efficacy is challenged by instability, intracellular aggregation, low uptake, and cytotoxicity. Here, we describe a series of hybrid lipid-coated gold nanorods (AuNRs) that could solve these issues. These nanomaterials were made via a layer-by-layer assembly approach, and their stability in biological media, mechanism, efficiency of uptake, and toxicity were compared with a commercially available set of AuNRs with a 5 nm mesoporous silica (mSiO2)-polymer coating. These nanomaterials can serve as stem cell labeling and OCT imaging agents because they absorb in the near-infrared (NIR) region away from biological tissues. Although both subtypes of AuNRs were taken up by retinal pigment epithelial, neural progenitor, and baby hamster kidney cells, slightly negatively charged hybrid lipid-coated AuNRs had minimal aggregation in biological media and within the cytoplasm of cells (∼3000 AuNRs/cell) as well as minimal impact on cell health. Hybrid lipid-coated AuNRs modified with cell-penetrating peptides had the least toxicological impact, with >92% cell viability. In contrast, the more "sticky" AuNRs with a 5 nm mSiO2-polymer coating showed significant aggregation in biological media and within the cytoplasm with lower-than-expected uptake of AuNRs (∼5400 of AuNRs/cell) given their highly positive surface charge (35+ mV). Collectively, we have demonstrated that hybrid lipid-coated AuNRs, which absorb in the NIR-II region away from biological tissues, with tuned surface chemistry can label therapeutic derived stem cells with minimal aggregation and impact on cell health as well as enhance uptake for OCT imaging applications.
KW - cell uptake studies
KW - cell-penetrating peptides
KW - lipid-coated gold nanorods
KW - optical coherence tomography imaging
KW - stem cells
KW - toxicity
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U2 - 10.1021/acsanm.2c00958
DO - 10.1021/acsanm.2c00958
M3 - Article
AN - SCOPUS:85131135801
SN - 2574-0970
VL - 5
SP - 6995
EP - 7008
JO - ACS Applied Nano Materials
JF - ACS Applied Nano Materials
IS - 5
ER -