Systems, methods, and biomaterials for radiation therapy

Abstract

Methods and systems for radiation therapy involve administering a payload / combination of biocompatible high-Z and semiconductor NPs to tissue, such as a tumor or an eye. Ionizing radiation may be directed towards the payload, and ionized electrons generate Cerenkov radiation (CR). The CR interacts with semiconductor NPs to produce chemical species that are damaging to cells. The payload may be administered via injection or via a radiotherapy (RT) device that includes NPs in a biodegradable polymer matrix. Biodegradation of the polymer matrix, which results in release of its payload, may be remotely activated using, for example, electromagnetic or sound waves. The payload may include one or more immunologic adjuvants capable of promoting an immunologic response at remote sites (such as a metastatic tumors) that are separate from the site at which the NPs and adjuvants were administered.

1 - 77 . (canceled) 
     
     
         78 . A radiation therapy method comprising:
 administering a payload comprising first high z nanoparticles (NPs) and second semiconductor NPs to a tissue site of a subject; and   applying an ionizing first radiation directed at the site at which the payload was administered;   wherein a second radiation is generated via interaction of the first high z NPs with the first radiation;   wherein chemical species are generated via interaction of the second semiconductor NPs with the second radiation;   wherein the chemical species are damaging to one or more cells at the tissue site, and   wherein the first high z NPs include NPs comprising an element having an atomic number of at least 26.   
     
     
         79 . The method of  claim 78 , wherein the first high z NPs include NPs comprising an element having an atomic number of between 26 and 79. 
     
     
         80 . The method of  claim 78 , wherein the first high z NPs comprise at least one of gold NPs, gadolinium NPs, or iron oxide NPs. 
     
     
         81 . The method of  claim 78 , wherein the second semiconductor NPs are metal oxide NPs. 
     
     
         82 . The method of  claim 81 , wherein the second semiconductor NPs include NPs selected from the group consisting of titanium oxide and zinc oxide. 
     
     
         83 . The method of  claim 78 , wherein the second semiconductor NPs are doped with an image contrast agent. 
     
     
         84 . The method of  claim 78 , wherein the first high z NPs emit electrons via photoelectric interaction with the first radiation. 
     
     
         85 . The method of  claim 84 , wherein the electrons are damaging to one or more cells at the site. 
     
     
         86 . The method of  claim 78 , wherein the first radiation is x-radiation. 
     
     
         87 . The method of  claim 78 , wherein the second radiation is Cerenkov radiation. 
     
     
         88 . The method of  claim 87 , wherein the first high z NPs emit electrons via photoelectric interaction with the first radiation, and wherein the Cerenkov radiation is generated via interaction of the electrons with tissue of the subject. 
     
     
         89 . The method of  claim 78 , wherein the payload is administered via injection. 
     
     
         90 . The method of  claim 78 , wherein the payload is administered via a radiotherapy (RT) device. 
     
     
         91 . The method of  claim 90 , wherein the RT device includes a device selected from the group consisting of a fiducial marker, a radiotherapy spacer, and a radiotherapy beacon. 
     
     
         92 . The method of  claim 90 , wherein the RT device includes a hollow core. 
     
     
         93 . The method of  claim 92 , wherein at least a portion of the payload is situated in the hollow core. 
     
     
         94 . The method of  claim 90 , wherein the RT device includes a polymer matrix. 
     
     
         95 . The method of  claim 94 , wherein the polymer matrix includes a polymer selected from the group consisting of PLGA and chitosan. 
     
     
         96 . The method of  claim 94 , wherein the polymer matrix is biodegradable, wherein the RT device releases at least a portion of the payload via biodegradation of the polymer matrix, and wherein biodegradation of the polymer matrix is remotely activated by a stimulator. 
     
     
         97 . The method of  claim 78 , wherein the first radiation is delivered via a local radiation source comprising an implanted x-ray emitting radioisotope. 
     
     
         98 . The method of  claim 78 , wherein the first radiation is delivered via external beam radiotherapy (EBRT). 
     
     
         99 . The method of  claim 78 , wherein the payload further includes one or more immunologic adjuvants. 
     
     
         100 . The method of  claim 78 , wherein the chemical species are reactive oxygen species (ROS). 
     
     
         101 . A radiation therapy method comprising:
 administering a payload comprising high z nanoparticles (NPs) and semiconductor NPs to a tissue site of a subject; and   applying a megavolt ionizing radiation directed at the site at which the payload was administered via an external radiation beam;   wherein a Cerenkov radiation is generated via interaction of the megavolt ionizing radiation with the high z NPs at the tissue site;   wherein chemical species are generated via interaction of the semiconductor NPs with the Cerenkov radiation;   wherein the chemical species are damaging to one or more cells at the tissue site, and   wherein the high z NPs include NPs comprising an element having an atomic number of at least 26.   
     
     
         102 . The method of  claim 101 , wherein the high z NPs include NPs comprising an element having an atomic number of between 26 and 79. 
     
     
         103 . The method of  claim 101 , wherein the high z NPs comprise at least one of gold NPs, gadolinium NPs, or iron oxide NPs. 
     
     
         104 . The method of  claim 101 , wherein the semiconductor NPs include NPs selected from the group consisting of titanium oxide and zinc oxide. 
     
     
         105 . The method of  claim 101 , wherein the payload further includes an immunologic adjuvant. 
     
     
         106 . The method of  claim 101 , wherein the chemical species are reactive oxygen species generated via interaction of the semiconductor NPs with the Cerenkov radiation.