Abstract
Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of −38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0%–43.7% at nanogel concentrations of 0.05–0.5 mg/mL and rabbit aorta endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition of 8.0%–22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.
Highlights
Nanoparticles have attracted significant attention due to their various applications in the fields of biotechnology and biomedical sciences
Characteristic sulfate absorptions were identified in the Fourier Transformed Infrared Spectroscopy (FT-IR) spectra of compounds: bands around 1274 cm−1 for asymmetric S=O stretching vibration and bands around 1045 cm−1 for symmetric C–O vibration associated with a C–O–SO3 group
The SNFuc FI-IR spectrum showed the intensity of these bands increased due the presence of N–H (3000–3400 cm−1) and stretching vibrations of CH2 in hexadecyl residues (2921 and around 2850 cm−1) [21]
Summary
Nanoparticles have attracted significant attention due to their various applications in the fields of biotechnology and biomedical sciences. The term nanogel is frequently used to define aqueous dispersions of hydrogel particles composed of nanoscale-sized physically or chemically cross-linked polymer networks [1]. Their application in medicine is very promising since they exhibit high stability and loading capacity, as well as responsiveness to environmental factors such as pH, ionic strength and temperature, making them viable candidates for transport and drug release. When nanoparticles enter the bloodstream they are often opsonized by plasma proteins and/or rapidly removed from the blood by the mononuclear phagocytic system [2]. Hydrophobic particles are typically opsonized much faster than their hydrophilic counterparts [3]. Some polymers have been evaluated as protecting groups, including polyacrylamides, polyvinyl alcohol (PVA), poly(ethylene glycol) (PEG) and polysaccharides [4]
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