Method and composition for hyperthermally treating cells
A method and composition for hyperthermally treating tumor cells in a patient under conditions that affect tumor stem cells and tumor cells. In one embodiment, the method provides a synergetic effect with chemotherapy.
1. A method of drug delivery and thermal damage to target tumor cells in a patient in need thereof, the method comprising
administering anti-tumor antibody specific coated drug containing nanoparticles to a patient in need thereof, the nanoparticles forming an antibody labeled nanoparticle-cell complex at a target site,
thereafter locally administering thermal therapy at the tumor site containing the anti-tumor antibody specific coated drug containing nanoparticles wherein the nanoparticles respond by expanding thus generating a an acoustic signal,
measuring the acoustic signal and relating the measured signal to
a first temperature at the nanoparticle tumor cell complex and thereafter a second temperature at the nanoparticle tumor cell complex, and
controlling the temperature of the nanoparticle tumor cell complex from at least 37° C. to 43° C. for the first temperature for an initial stage of thermotherapy, and at least one of 43° C. to 58° C., 43° C. to 45° C., 43° C. to 58° C., 45° C. to 50° C., 50° C. to 58° C., 58° C. to 60° C., greater than 58° C., or greater than 60° C. for the second temperature, based on the acoustic signal,
the thermotherapy resulting in specific drug delivery and thermal damage to tumor cells.
2. The method of claim 1 where the thermal therapy is limited to the nanoparticle tumor cell complex site and does not substantially affect normal cells proximate to the tumor.
3. The method of claim 1 where the thermal therapy is provided by at least one of electromagnetic radiation, ultrasound energy, alternating magnetic field.
4. The method of claim 1 where the anti-tumor antibody specific coated nanoparticles further comprises a known thermal sensitive polymer, resulting in release of a chemotherapeutic agent contained in the nanoparticle by dissociation of the polymer when the thermal sensitive temperature is reached by the initial stage of thermotherapy.
5. The method of claim 1 performed on the patient receiving at least one of chemotherapy, radiation therapy, anti-vascular endothelial growth-factor therapy, or steroid therapy.
6. The method of claim 1 further comprising imaging the tumor site after therapy and optionally repeating the method based on the imaging results.
7. The method of claim 6 where imaging comprises thermal imaging, photoacoustic imaging, X-ray imaging, optical coherence tomography, ultrasound imaging, fluorescence imaging, chemiluminescent imaging, positron imaging, surface enhanced Raman spectroscopy, and/or magnetic resonance imaging.
8. A method of targeting tumor stem cells for therapy in a patient in need thereof, the method comprising
combining chemotherapy with thermotherapy by
administering anti-tumor antibody specific coated drug containing nanoparticles to a patient in need thereof, the nanoparticles forming an antibody labeled nanoparticle-cell complex at a target site,
thereafter locally administering thermal therapy at the tumor site containing the anti-tumor antibody specific coated drug containing nanoparticles wherein the nanoparticles respond by expanding thus generating a an acoustic signal,
measuring the acoustic signal and relating the measured signal to
a first temperature of the nanoparticle tumor cell complex and thereafter a second temperature of the nanoparticle tumor cell complex, and
controlling the temperature of the nanoparticle tumor cell complex from at least 37° C. to 43° C. for the first temperature for an initial stage of thermotherapy, and at least one of 43° C. to 58° C., 43° C. to 45° C., 43° C. to 58° C., 45° C. to 50° C., 50° C. to 58° C., 58° C. to 60° C., greater than 58° C., or greater than 60° C. for the second temperature, based on the acoustic signal,
the tumor thermotherapy being a stepwise increase in temperature that at relatively lower temperatures primes the tumor stem cells for increased susceptibility to the chemotherapy then, at relatively higher temperatures, kills the primed tumor stem cells with a synergistic combination of the chemotherapy and the thermotherapy.
9. The method of claim 8 where the patient has undergone chemotherapy prior to the thermotherapy.
10. The method of claim 8 where the patient is simultaneously undergoing chemotherapy with the thermotherapy.
11. A method of providing thermotherapy to a cancer patient, the method comprising
(a) administering to a cancer patient in need thereof a composition comprising at least one biocompatible excipient and a liposome, where the liposome comprises at least one nanoparticle and at least one anticancer drug, optionally conjugated to the at least one nanoparticle, under conditions to provide a concentration of the anticancer drug at a target site sufficient to be amenable to thermal therapy, and
(b) providing an energy source wherein the nanoparticles respond by expanding thus generating an acoustic signal,
(c) measuring the acoustic signal and relating the measured signal to a first temperature of the nanoparticle at the tumor site and a second temperature of the nanoparticle tumor site, and controlling the temperature of the nanoparticle from at least 37° C. to 43° C. for the first temperature and 43° C. to 58° C., greater than 58° C., or greater than 60° C. for the second temperature, based on the acoustic signal to hyperthermally treat cells,
the thermotherapy resulting in specific staged drug delivery and thermal damage to tumor cells.
12. The method of claim 11 further comprising administering a labeled composition in (a) and then (d) optionally imaging the target site.
13. The method of claim 12 where the composition in (a) contains a magnetic, diamagnetic, ferromagnetic, and/or paramagnetic nanoparticle.
14. The method of claim 12 where the optional imaging step is by magnetic resonance imaging.
15. The method of claim 11 where the composition administered in (a) contains a gold nanoparticle, diamond nanoparticle, platinum nanoparticle, and/or carbon nanoparticle.
16. The method of claim 11 where the energy source provided in (b) is limited to the nanoparticle tumor cell complex site and does not affect normal cells proximate to the target site.