Nanobubbles
The present invention provides a nanobubble comprising a continuous outer shell, the outer shell comprising a cross-linked polymeric material, an inner wall of the continuous outer shell and a hollow core within the continuous outer shell. The nanobubble may be less than 250 nm in diameter. In a further aspect of the invention, the cross-linked polymeric material is a cellulose-based material.
1. A nanobubble composition at about 0.5 mg/ml to about 1 mg/ml for controlled ultrasound activated cargo release in targeted cells, wherein the ultrasound activated cargo release changes said cells' 5 mC level and gene expression pattern, wherein the nanobubble composition is made by:
providing a homogenized gel consisting of a cellulose based material at about 0.1% to about 2% w/v,
saturating the homogenized gel with oxygen and optionally with cargos under continuous sonication to produce nanobubbles,
cross-linking the homogenized gel, nanobubbles and cargos with a trivalent cross-linker at about 0.1% to about 1% to form an encapsulated structure, wherein said encapsulated structure comprises a continuous outer shell and an inner wall of the continuous outer shell, wherein the continuous outer shell and inner wall encapsulate cargos selected from the group consisting of fluorophore, a pharmaceutical, a biomolecule, a ligand, contrast imaging agents, antibodies, lipids, protein receptors, aptamers or combinations thereof; and
a hollow core, wherein the hollow core is filled with oxygen, and
wherein the nanobubble is less than about 250 nm in diameter.
2. The nanobubble of claim 1 wherein the cellulose based material comprises sodium carboxymethyl cellulose, polyethylene glycol, chitosan sodium hyaluronate, poly(lactic-co-glycolic acid, polystyrene, hydrogels, sodium starch glycolate, poly(vinyl pyrrolidone), microcrystalline cellulose, hydroxypropylmethyl cellulose, HPMC phthalate, oxycellulose, sodium stearyl fumarate, alpha cellulose, pre-gelatinized starch, starch acetate, albumin, dextran, chitosan or combination thereof.
3. The nanobubble of claim 1 wherein the nanobubble is less than about 200 nm in diameter.
4. The nanobubble of claim 1 wherein the nanobubble is less than about 100 nm in diameter.
5. The nanobubble of claim 1 wherein the nanobubble is less than about 50 nm in diameter.
6. The nanobubble of claim 1 wherein the nanobubble bursts at a frequency of about 1.1 MHz over a range of about 0.01 to about 1100 mv/cm 3 .
7. The nanobubble of claim 6 wherein about 50 percent of the nanobubble will burst at 70 mv/cm 3 .
8. The nanobubble of claim 1 wherein the hollow core and the outer shell have pores.
9. A method of controlled delivery of a cargo to a cell, comprising:
providing a nanobubble of claim 1 to the cell;
providing a form of energy at a given frequency or power or intensity of sound wave,
wherein the form of energy is configured to trigger the nanobubble of claim 1 to resonate and burst releasing the cargo to the cell.
10. The method of claim 9 wherein the form of energy is adjusted to trigger the bursting time.
11. The method of claim 9 wherein the nanobubble size and density is adjustable, with the size between about 50 nm to about 200 nm and the density between about 0.5 mg/ml to about 1 mg/ml.
12. The nanobubble composition of claim 1 , wherein the polymeric material is 0.1% w/v sodium carboxymethyl cellulose (NaCMC).
13. The nanobubble composition of claim 1 , wherein the cross-linker is 1% aluminum chloride (AlCl 3 ).