Treatments of disease or disorders using nanoparticles for focused hyperthermia to increase therapy efficacy

Abstract

Methods are provided for the treatment of diseases and disorders using systematically-introduced nanoparticles to create a focused localized hyperthermia in a target area to enhance the effect of additional treatment therapies such as ionizing radiation. Advantages include an enhancement of the therapeutic effect of other therapies by increasing perfusion or reducing hypoxia in the treatment area, further, the methods herein may also result in the disruption of the vasculature, which provide further impetus for such treatments, singly and in combination with conventional therapies such as chemotherapy and radiation therapy. Methods for treating a target area may comprise systemically introducing nanoparticles into an organism; allowing the nanoparticles to preferentially accumulate in the target area, applying an external energy where the nanoparticles are adapted to transduce at least a portion of the external energy into a heal energy so as to create a focused localized hyperthermia; and applying a subsequent additional therapy.

1 . A method for the treatment of cancer comprising
 the systemic delivery of energy-absorbing particles to a tumor,   the application of electromagnetic or mechanical energy to the area resulting in an elevated temperature in the tumor,   and the application of ionizing radiation to the tumor.   
     
     
         2 . The method of  claim 1  wherein the localized hyperthermia reduces the hypoxia of the tumor. 
     
     
         3 . The method of  claim 1  wherein the tumor vasculature is disrupted. 
     
     
         4 . The method of  claim 1  wherein the localized hyperthermia initially reduces the hypoxia of the tumor and the combined hyperthermia and radiation results in a disruption of the tumor vasculature. 
     
     
         5 . A method for the disruption of vasculature of a target area comprising
 the delivery of energy-absorbing particles to the target area,   the application of electromagnetic or mechanical energy to the area resulting in an elevated temperature in the vasculature of the target area,   and the application of ionizing radiation to the target area.   
     
     
         6 . A method for the disruption of vasculature of a target area comprising
 the application of electromagnetic energy in a wavelength absorbed by the blood component of the target area resulting in an elevated temperature in the vasculature of the target area,   and the application of ionizing radiation to the target area.   
     
     
         7 . A method for the treatment of tumors comprising:
 increasing the perfusion of tumors by   the delivery of energy-absorbing particles to the target area   followed by the application of electromagnetic or mechanical energy   resulting in an elevated temperature of the target area   and the delivery of a therapeutic agent to the tumor   wherein the efficacy is enhanced by the increased perfusion.   
     
     
         8 . The method of  claim 7  wherein the therapeutic agent is a chemotherapeutic drug. 
     
     
         9 . The method of  claim 7  wherein the therapeutic agent is a gene therapy vector. 
     
     
         10 . The method of  claim 7  wherein the therapeutic agent is a drug delivery vector. 
     
     
         11 . The method of  claim 10 . wherein the drug delivery vector is selected from among liposomes or micelles or hollow nanoparticles or drug eluting nanoparticles. 
     
     
         12 . The method of  claim 7  wherein the therapeutic agent is an immunotherapeutic agent. 
     
     
         13 . The method of  claim 7  wherein the therapeutic agent is vascular-targeted therapy. 
     
     
         14 . A method for the treatment of tumors comprising:
 increasing the hypoxia of tumors by   the systemic delivery of energy-absorbing particles to the target area   followed by the application of electromagnetic or mechanical energy   resulting in an elevated temperature of the target area,   followed by the application of ionizing radiation to the tumor,   resulting in the disruption of the vasculature of the tumor   and the delivery of a hypoxia-targeted therapy to the tumor.   
     
     
         15 . The method of  claim 14  wherein the hypoxia-targeted therapy is an anerobic bacterial spore. 
     
     
         16 . The method of  claim 14  wherein the hypoxia-targeted therapy is an inhibitor of HIF1 Alpha or thioredoxin. 
     
     
         17 . The method of  claim 1  wherein the energy-absorbing particles are selected from among, or are a combination of, nanoshells, nanorods, carbon nanotubes, fullerenes, paramagnetic particles, metallic nanoparticles, and other absorbers of electromagnetic energy or absorbers of acoustic energy. 
     
     
         18 . The method of  claim 5  wherein the energy-absorbing particles are selected from among, or are a combination of, nanoshells, nanorods, carbon nanotubes, fullerenes, paramagnetic particles, metallic nanoparticles, and other absorbers of electromagnetic energy or absorbers of acoustic energy. 
     
     
         19 . The method of  claim 7  wherein the energy-absorbing particles are selected from among, or are a combination of, nanoshells, nanorods, carbon nanotubes, fullerenes, paramagnetic particles, metallic nanoparticles, and other absorbers of electromagnetic energy or absorbers of acoustic energy. 
     
     
         20 . The method of  claim 14  wherein the energy-absorbing particles are selected from among, or are a combination of, nanoshells, nanorods, carbon nanotubes, fullerenes, paramagnetic particles, metallic nanoparticles, and other absorbers of electromagnetic energy or absorbers of acoustic energy.