Method and composition for hyperthermally treating cells
A method and composition for hyperthermally diagnosing and monitoring treatment of cells with photoacoustic sound and nanoparticles. The heat (temperature) and photoacoustic sound wave production inside the target tissue is measured. The desired temperature is achieved using a laser and photoacoustic imaging technique. Hyperthermia treatment of tissue applies a heat source to kill cells without protein denaturation. The hyperthermia treatment may further comprise platelet-derived treatment. The method introduces an encapsulated dye that is released at a selected temperature in the target site to indicate that a threshold temperature has been reached to hyperthermally treat the tissue. The temperature to which the target site is treated ranges from about 39° C. to about 58° C., and may last from about 5 seconds to about 30 minutes. The composition which can be a liposome composition encapsulating the dye can be introduced to the bloodstream to flow through the target site.
1. A method of treating a tumor in a patient without protein denaturation, the method comprising
i) introducing a composition comprising an antitumor-antibody-labeled nanoparticle wherein the nanoparticle forms an antibody labeled nanoparticle-cell complex at a tumor site,
ii) exposing the patient to an energy source wherein the nanoparticles respond by expanding thus generating an acoustic signal,
iii) measuring the acoustic signal and relating the measured signal to a temperature of the nanoparticle-cell complex, and
iv) controlling the temperature of the nanoparticle-cell complex from about 39° C. to about 58° C. based on the acoustic signal to hyperthermally damage or kill cells in the tumor.
2. The method of claim 1 where the exposing step is limited to the tumor site.
3. The method of claim 1 where the antitumor-antibody-labeled nanoparticle is introduced by direct injection at the tumor site or by indirect injection into a bodily fluid.
4. The method of claim 1 where the antitumor-antibody-labeled nanoparticle is magnetic, diamagnetic, ferromagnetic, paramagnetic, or combinations thereof.
5. The method of claim 1 where the antitumor-antibody-labeled nanoparticle contains at least one (poly)ethylene glycol moiety.
6. The method of claim 1 further comprising performing extracorporeal dialysis on the patient under conditions to remove a protein of the tumor.
7. The method of claim 1 where the nanoparticle is gold, diamond, platinum, carbon, a quantum dot, or combinations thereof.
8. The method of claim 1 where the energy source is electromagnetic radiation or a magnetic field energy source.
9. The method of claim 8 comprising magnetic nanoparticles where the energy source is an alternating magnetic field.
10. The method of claim 9 where the magnetic field ranges from 0.0001 Tesla (T) to 13 T or from 0.0001 T to 11 T.
11. The method of claim 8 where the electromagnetic radiation is between 350 nm to 1300 nm.
12. The method of claim 8 where the electromagnetic radiation is between 450 nm to 600 nm.
13. The method of claim 1 where the nanoparticle size is between 2 nm to 700 nm.
14. The method of claim 13 where the nanoparticle size is between 50 nm to 250 nm.
15. The method of claim 1 such that the temperature is maintained from about 1 minute to about 30 minutes.
16. The method of claim 1 wherein the acoustic signal is measured with an acoustic wave sensor or an acoustic wave detector.
17. The method of claim 1 further comprising imaging the tumor site.
18. The method of claim 17 where imaging is by at least one of photoacoustic imaging, magnetic resonance imaging, X-ray imaging, optical coherence tomography, ultrasound imaging, fluorescence imaging, positron imaging, and surface enhanced Raman spectroscopy.
19. The method of claim 1 where the temperature ranges from about 39° C. to about 45° C., or from about 45° C. to about 49° C., or from about 49° C. to about 56° C.
20. The method of claim 1 further comprising providing the method to the patient in conjunction with chemotherapy, radiation therapy, anti-vascular endothelial growth-factor therapy, steroid therapy, or combinations thereof.
21. The method of claim 1 where the energy source is microwave radiation or radiofrequency radiation.
22. The method of claim 1 wherein a temperature indicating substance comprising a first fluorescent dye encapsulated in a first temperature sensitive liposome, and a second fluorescent dye encapsulated in a second temperature sensitive liposome, are provided with the nanoparticles, wherein the first fluorescent dye is released from the first liposome when heating to a temperature of at least 42° C. but below the protein denaturation temperature to indicate an effective temperature for hyperthermally treating the tissue without releasing the second fluorescent dye from the second liposome, and wherein the second fluorescent dye is released from the second liposome to indicate a higher temperature but before a protein denaturation temperature is exceeded.
23. The method of claim 22 in which an agent for chemotherapy, radiation therapy, anti-vascular endothelial growth-factor therapy, steroid therapy, or combinations thereof is included with the first fluorescent dye.
24. A method of treating an infectious agent in a patient, the method comprising
i) introducing a composition comprising an antiinfectious agent-antibody-labeled nanoparticle and a temperature indicating substance, wherein the nanoparticle forms an antiinfectious agent-antibody-labeled nanoparticle-cell complex in the patient,
ii) exposing the patient to an energy source wherein the nanoparticles respond by expanding thus generating an acoustic signal,
iii) measuring the acoustic signal and relating the measured signal to a temperature of the nanoparticle-cell complex, and
iv) controlling the temperature of the nanoparticle-cell complex from about 40° C. to about 49° C. based on the acoustic signal to hyperthermally treat the infectious agent, destroying or rendering the infectious agent inactive.
25. A method of ameliorating a neurodegenerative process in a patient, the method comprising
i) introducing a composition comprising an anti-neurodegenerative protein antibody-labeled nanoparticle and a temperature indicating substance into blood, brain, or cerebrospinal fluid of a patient, wherein the nanoparticle forms an anti-neurodegenerative protein-labeled nanoparticle complex at a target site in the patient,
ii) exposing the patient to an energy source wherein the nanoparticles respond by expanding thus generating an acoustic signal,
iii) measuring the acoustic signal and relating the measured signal to a temperature of the nanoparticle-cell complex based on the acoustic signal, and
iv) controlling the temperature of the nanoparticle complex from about 39° C. to about 55° C. based on the acoustic signal to hyperthermally treat the target site, reducing, preventing aggregation of, or destroying the neurodegenerative protein.
26. The method of claim 25 where the neurodegenerative protein of the anti-neurodegenerative protein antibody is beta amyloid protein.