Spherical and rod-shaped gold nanoparticles with surface poly (ethylene glycol) (PEG) chains were characterized for size, shape, charge, poly dispersity and surface plasmon resonance. The nanoparticles were injected intravenously to 6-8 weeks old female nu/nu mice bearing orthotopic ovarian tumors and their biodistribution in vital organs was compared. Gold nanorods were taken up to a lesser extent by the liver, had longer circulation time in the blood, and higher accumulation in the tumors, compared with their spherical counterparts. The cellular uptake of PEGylated gold nanoparticles by a murine macrophage-like cell line as a function of geometry was examined. Compared to nanospheres, PEGylated gold nanorods were taken up to a lesser extent by macrophages. These studies point to the importance of gold nanoparticle geometry and surface properties on transport across biological barriers.
Using a series of gold nanoparticles with incremental increase in dimensions but varying geometries (spherical vs rods) we have evaluated the infl uence of shape, size, surface properties and concentration on cellular uptake, adsorption of proteins and toxicity in a human prostate cancer cell line (PC-3). In the range of 30-90 nm diameter studied, spherical particles of 50 nm in diameter without polyethylene glycol (PEG) had the highest uptake. Surface attachment of PEG reduced cellular uptake. PEGylated gold nanorods had a net positive charge compared with their spherical counterparts and particle geometry infl uenced cellular uptake. In the absence of serum proteins the uptake of plain spherical GNPs increased. These studies pave the way for the tailoring of gold nanoparticles for targeted tumor therapy applications.
Nanocarriers responding to light have great potential for pinpoint therapy, and recent studies have revealed promising in vivo activity. However, light-selective gene transfer still remains challenging in the systemic application. Here we report systemic light-responsive nanocarriers for gene delivery developed through the sequential self-assembly of ABC-type triblock copolymer/DNA/dendrimeric photosensitizer, forming polyplex micelles with three-layered functional nanocompartments. The DNA-packaged core is covered by the photosensitizer-incorporated intermediate layer, which is encompassed by an outer shielding shell. This three-layered structure permits multistep photosensitizer and DNA delivery into a solid tumour by a systemic route: the shielding layer minimizes unfavourable interactions with blood components, and the photosensitizer is delivered to endo-/lysosomal membranes to facilitate light-selective cytoplasmic translocation of the micelles, accomplishing DNA delivery into the nucleus to exert gene expression. The polyplex micelles display 4100-fold photoenhanced gene expression in cultured cells and exhibit light-induced in vivo gene transfer in solid tumours following systemic administration.
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