IN VIVO PHOTOACOUSTIC AND PHOTOTHERMAL NANO-THERANOSTICS OF BIOFILMS
A composition and methods for the non-invasive destruction of bacteria cells in vivo using a combination therapy of antibiotics and photothermal nano-theranostics. In one aspect, a composition and method for destroying at least one bacteria cell using a functionalized PA contrast agent with a targeting agent, coating, and antibiotic that uses photoacoustic signals to create thermal energy and release the loaded antibiotic are described.
1 . A method for selectively destroying at least one bacterial cell within a subject in vivo, comprising:
contacting at least one functionalized nanoconstruct with the at least one bacterial cell, wherein the at least one functionalized nanoconstruct comprises:
at least one PA contrast agent;
a coating on the surface of the at least one PA contrast agent;
at least one targeting agent linked to the at least one PA contrast agent or the coating; and
at least one antibiotic loaded on the coating;
triggering at least one ablation laser pulse delivered at a wavelength and energy level sufficient to cause destruction of at least one bacterial cell; and
releasing the at least one antibiotic from the functionalized nanoconstruct.
2 . The method of claim 1 , further comprising:
directing at least one detection laser pulse into an area of interest containing the at least one bacterial cell; and
detecting at least one photoacoustic signal emitted by the at least one PA contrast agent bound to a targeting moiety on the at least one bacterial cell via the targeting agent.
3 . The method of claim 2 , further comprising:
monitoring a frequency of detection of a remaining portion of bacterial cells; and
terminating when the frequency of detection of the remaining portion of bacterial cells falls below a threshold level.
4 . The method of claim 1 , wherein the at least one PA contrast agent is selected from the group consisting of: gold nanospheres, gold nanoshells, gold nanorods, gold nanocages, carbon nanoparticles, perfluorocarbon nanoparticles, carbon nanotubes, spectrally tunable golden carbon nanotubes, carbon nanohorns, magnetic nanoparticles, silica-coated magnetic nanoparticles, quantum dots, binary gold-carbon nanotube nanoparticles, multilayer nanoparticles, clustered nanoparticles, liposomes, micelles, and microbubbles.
5 . The method of claim 3 , wherein the at least one PA contrast agent is gold nanocages.
6 . The method of claim 1 , wherein the at least one targeting agent comprises an antibody, a protein, a ligand for one or more specific cell receptors, a receptor, a peptide, or a wheat germ agglutinin.
7 . The method of claim 1 , wherein the at least one targeting agent is selected from the group consisting of antibodies to protein A receptors of Staphylococcus aureus , antibodies to a lipoprotein, ligands to polysaccharide and siderophore receptors of a bacteria, and an antibody specific for a protein highly expressed in the bacteria but absent in mammalian cells.
8 . The method of claim 6 , wherein the at least one bacterial cell is chosen from: Clostridium difficile ; Carbapenem-resistant Enterobacteriaceae (CRE); drug-resistant Neisseria gonorrhoeae ; multidrug-resistant Acinetobacter ; drug-resistant Campylobacter ; extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs); vancomycin-resistant Enterococcus (VRE); multidrug-resistant Pseudomonas aeruginosa ; drug-resistant non-typhoidal Salmonella ; drug-resistant Salmonella typhi ; drug-resistant Shigella ; methicillin-resistant Staphylococcus aureus (MRSA); drug-resistant Streptococcus pneumoniae ; drug-resistant tuberculosis; vancomycin-resistant Staphylococcus aureus (VRSA); erythromycin-resistant Group A Streptococcus ; clindamycin-resistant Group B Streptococcus; Staphylococcus epidermis ; and any combination thereof.
9 . The method of claim 1 , wherein the at least one antibiotic comprises daptomycin.
10 . The method of claim 1 , wherein the coating comprises polydopamine.
11 . The method of claim 3 , wherein the at least one detection laser pulse comprises a first wavelength used with a first PA contrast agent to detect the at least one bacteria cell and the at least one ablation laser pulse comprises a second wavelength used with a second PA contrast agent to destroy the at least one bacteria cell.
12 . The method of claim 1 , wherein the at least one functionalized nanoconstruct is contacted with the at least one bacterial cell using injection at an injection site of the subject.
13 . A functionalized nanoconstruct for selectively destroying at least one bacterial cell within a subject in vivo, comprising:
at least one PA contrast agent;
a coating on the surface of the at least one PA contrast agent;
at least one targeting agent linked to the at least one PA contrast agent or the coating; and
at least one antibiotic loaded on the coating,
wherein the at least one functionalized nanoconstruct binds to a targeting moiety on the at least one bacterial cell via the targeting agent.
14 . The functionalized nanoconstruct of claim 13 , wherein the at least one PA contrast agent is selected from the group consisting of: gold nanospheres, gold nanoshells, gold nanorods, gold nanocages, carbon nanoparticles, perfluorocarbon nanoparticles, carbon nanotubes, spectrally tunable golden carbon nanotubes, carbon nanohorns, magnetic nanoparticles, silica-coated magnetic nanoparticles, quantum dots, binary gold-carbon nanotube nanoparticles, multilayer nanoparticles, clustered nanoparticles, liposomes, micelles, and microbubbles.
15 . The functionalized nanoconstruct of claim 14 , wherein the at least one PA contrast agent is gold nanocages.
16 . The functionalized nanoconstruct of claim 13 , wherein the at least one targeting agent is selected from the group consisting of antibodies to protein A receptors of Staphylococcus aureus , antibodies to a lipoprotein, ligands to polysaccharide and siderophore receptors of a bacteria, and an antibody specific for a protein highly expressed in a bacteria but absent in mammalian cells.
17 . The functionalized nanoconstruct of claim 16 , wherein the at least one bacterial cell is chosen from: Clostridium difficile ; Carbapenem-resistant Enterobacteriaceae (CRE); drug-resistant Neisseria gonorrhoeae ; multidrug-resistant Acinetobacter ; drug-resistant Campylobacter ; extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs); vancomycin-resistant Enterococcus (VRE); multidrug-resistant Pseudomonas aeruginosa ; drug-resistant non-typhoidal Salmonella ; drug-resistant Salmonella typhi ; drug-resistant Shigella ; methicillin-resistant Staphylococcus aureus (MRSA); drug-resistant Streptococcus pneumoniae ; drug-resistant tuberculosis; vancomycin-resistant Staphylococcus aureus (VRSA); erythromycin-resistant Group A Streptococcus ; clindamycin-resistant Group B Streptococcus; Staphylococcus epidermis ; and any combination thereof.
18 . The functionalized nanoconstruct of claim 13 , wherein the at least one antibiotic comprises daptomycin.
19 . The functionalized nanoconstruct of claim 13 , wherein the coating comprises polydopamine.
20 . The functionalized nanoconstruct of claim 13 , wherein the at least one functionalized nanoconstruct is contacted with the at least one bacteria cell using injection at an injection site of the subject.