PURPOSE: Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain - (16-mercaptohexadecyl)trimethylammonium bromide (MTAB). METHODS: Step-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation. RESULTS: Fourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of OEG+GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm2) of femtosecond laser irradiation than the alkanethiol MTAB. CONCLUSION: OEG+GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.

• Klíčová slova
• cellular uptake, gold nanorods, oligoethylene glycol, photothermal stability, quaternary ammonium salts,
• MeSH
• biologický transport MeSH
• HeLa buňky MeSH
• hydrofobní a hydrofilní interakce MeSH
• koloidy MeSH
• kvartérní amoniové sloučeniny chemie   MeSH
• lidé MeSH
• ligandy MeSH
• nanotrubičky chemie   MeSH
• polyethylenglykoly chemie   MeSH
• stabilita léku MeSH
• teplota * MeSH
• zlato chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• koloidy MeSH
• kvartérní amoniové sloučeniny MeSH
• ligandy MeSH
• polyethylenglykoly MeSH
• zlato MeSH

BACKGROUND: Poly-l-lysine (PLL) enhances nanoparticle (NP) uptake, but the molecular mechanism remains unresolved. We asked whether PLL may interact with negatively charged glycoconjugates on the cell surface and facilitate uptake of magnetic NPs (MNPs) by tumor cells. METHODS: PLL-coated MNPs (PLL-MNPs) with positive and negative ζ-potential were prepared and characterized. Confocal and transmission electron microscopy was used to analyze cellular internalization of MNPs. A colorimetric iron assay was used to quantitate cell-associated MNPs (MNPcell). RESULTS: Coadministration of PLL and dextran-coated MNPs in culture enhanced cellular internalization of MNPs, with increased vesicle size and numbers/cell. MNPcell was increased by eight- to 12-fold in response to PLL in a concentration-dependent manner in human glioma and HeLa cells. However, the application of a magnetic field attenuated PLL-induced increase in MNPcell. PLL-coating increased MNPcell regardless of ζ-potential of PLL-MNPs, whereas magnetic force did not enhance MNPcell. In contrast, epigallocatechin gallate and magnetic force synergistically enhanced PLL-MNP uptake. In addition, heparin, but not sialic acid, greatly reduced the enhancement effects of PLL; however, removal of heparan sulfate from heparan sulfate proteoglycans of the cell surface by heparinase III significantly reduced MNPcell. CONCLUSION: Our results suggest that PLL-heparan sulfate proteoglycan interaction may be the first step mediating PLL-MNP internalization by tumor cells. Given these results, PLL may facilitate NP interaction with tumor cells via a molecular mechanism shared by infection machinery of certain viruses.

• Klíčová slova
• glycoconjugate, heparan sulfate proteoglycan, magnetic nanoparticles, poly-l-lysine, tea catechin,
• MeSH
• buněčná membrána metabolismus   MeSH
• dextrany chemie   metabolismus   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• gliom farmakoterapie   patologie   MeSH
• HeLa buňky MeSH
• heparansulfát proteoglykany chemie   metabolismus   MeSH
• lidé MeSH
• magnetické nanočástice aplikace a dávkování   chemie   MeSH
• magnetické pole MeSH
• nádorové buněčné linie MeSH
• polylysin chemie   metabolismus   farmakokinetika   MeSH
• polysacharid-lyasy metabolismus   MeSH
• transmisní elektronová mikroskopie MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dextrany MeSH
• heparansulfát proteoglykany MeSH
• heparitinsulfate lyase MeSH Prohlížeč
• magnetické nanočástice MeSH
• polylysin MeSH
• polysacharid-lyasy MeSH
• železo MeSH