Gold nanorods (AuNRs) possess unique photothermal properties due to their strong plasmonic absorption in the near-infrared region of the electromagnetic spectrum. They have been explored widely as an alternative or a complement to chemotherapy in cancer treatment. However, the use of AuNRs as an injectable medicine is greatly hindered by their stability in biological media. Therefore, studies have been focused on improving the stability of AuNRs by introducing biocompatible surface functionalizations such as polyethylene glycol (PEG) coatings. However, these coatings can affect heat conduction and alter their photothermal behavior. Herein, we studied how functionalization of AuNRs with PEG chains of different molecular weights determined the temperature distribution of suspensions under near-infrared irradiation, cell uptake in vitro , and hyperthermia-induced cytotoxicity. Thermogravimetric analysis of the PEG-conjugated AuNRs exhibited slightly different PEG mass fractions of 12.0%, 12.7%, and 18.5% for PEG chains with molecular weights of 2, 5, and 10 kDa, respectively, implying distinct structures for PEG brushes. When exposed to near-infrared radiation, we found greater temperatures and temperature gradients for longer PEG chains, while rapid aggregation was observed in unmodified (raw) AuNRs. The effect of the PEG coating on heat transport was investigated using molecular dynamics simulations, which revealed the atomic scale structure of the PEG brushes and demonstrated lower thermal conductivity for PEG-coated AuNRs than for unmodified AuNRs. We also characterized the uptake of the AuNRs into mouse melanoma cells in vitro and determined their ability to kill these cells when subjected to near-infrared radiation. For all PEG-coated AuNRs, exposure to 10 s of near-infrared radiation significantly reduced cell viability relative to unirradiated controls, with this viability further decreasing with increasing AuNR doses, indicating potential phototherapeutic effects. The 5 kDa PEG coating appeared to yield the best performance, yielding significant phototoxicity at even the lowest dose considered (0.5 μg mL −1 ), while also exhibiting high colloidal stability, which could help in rational design consideration of AuNRs for NIR induced photothermal therapy.
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Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes
Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.
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- Award ID(s):
- 1750607
- NSF-PAR ID:
- 10319865
- Date Published:
- Journal Name:
- Membranes
- Volume:
- 11
- Issue:
- 8
- ISSN:
- 2077-0375
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/membranes11080572
