Systems and methods for particle radiation enhanced delivery of therapy

Abstract

Systems and methods for enhancing the selective targeting of agents for preferential action at a target with reduced action with healthy tissue distal the target tissue. One or more agents can be combined with nano scale structures/particles for delivery to the target tissue. Appropriate bombardment with accelerated particle radiation, such as proton radiation, induces the release of the agents at the target site. Nano carriers can be combined with therapeutic and/or imaging enhancement agents. Imaging of the target tissue can provide a verification of the delivered dose of particle radiation. Nanocarriers can be provided with an outer shell selected for biocompatibility and durability in the in vivo environment and further selected to provide a feedback mechanism in the treatment environment to accelerate the release of the agent and reduce a total radiation dose needed for that release.

1 . An in vivo agent delivery vehicle comprising:
 a nano structure;   an in vivo agent comprising a layer arranged around the exterior of the nanostructure such that the in vivo-agent can be durably entrained within living tissue and wherein bombardment with a selected dose of particle radiation releases the in vivo agent from the nano structure; and   an outer coating such that the in vivo agent layer is interposed between the nanostructure and the outer coating.   
     
     
         2 . The in vivo agent delivery vehicle of  claim 1 , wherein the nanostructure comprises a gold nanoparticle. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The in vivo agent delivery vehicle of  claim 1 , wherein the in vivo agent delivery vehicle is configured to release the in vivo agent upon bombardment with proton radiation. 
     
     
         6 . The in vivo agent delivery vehicle of  claim 1 , wherein the nanostructure comprises one or more internal voids and wherein the in vivo agent is contained at least partially within the one or more voids. 
     
     
         7 . The in vivo agent delivery vehicle of  claim 1 , wherein the in vivo agent comprises a therapeutic agent. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The in vivo agent delivery vehicle of  claim 1 , wherein the in vivo agent comprises antibodies selected for tumor antigens. 
     
     
         11 - 18 . (canceled) 
     
     
         19 . An in vivo agent delivery vehicle comprising:
 a nanostructure comprising one or more internal voids; and   an in vivo agent contained at least partially within the one or more voids such that the in vivo-agent can be durably entrained within living tissue and wherein bombardment with a selected dose of particle radiation releases the in vivo agent from the nanostructure.   
     
     
         20 . The in vivo delivery vehicle of claim  18 , wherein the nanostructure comprises a gold particle. 
     
     
         21 . The in vivo agent delivery vehicle of claim  18 , wherein the in vivo agent delivery vehicle is configured to release the in vivo agent upon bombardment with proton radiation. 
     
     
         22 . The in vivo agent delivery vehicle of claim  18 , wherein the in vivo agent comprises a therapeutic agent. 
     
     
         23 . The in vivo agent delivery vehicle of claim  18 , wherein the in vivo agent comprises antibodies selected for tumor antigens. 
     
     
         24 . The in vivo agent delivery vehicle of claim  18 , wherein the in vivo agent comprises a layer arranged about an exterior of the nanostructure. 
     
     
         25 . The in vivo agent delivery vehicle of  claim 24 , further comprising an outer coating such that the in vivo agent layer is interposed between the nanostructures and the outer coating. 
     
     
         26 . An in vivo agent delivery vehicle comprising:
 an in vivo agent for entraining within a target tissue;   an outer coating selected to enhance biocompatibility of the in vivo agent delivery vehicle; and   a nanostructure for bombardment by particle radiation, the particle radiation being directed along one or more desired treatment vectors and characterized by a Bragg Peak being provided such that the Bragg peak can be employed to preferentially localize activation and release of the in vivo agent, thereby reducing undesired transfer of radiation energy to tissue upstream or downstream of the target tissue along the one or more vectors;   wherein the in vivo agent is engaged with the nanostructure and the in vivo agent is interposed between the nanostructure and the outer coating.   
     
     
         27 . The in vivo agent delivery vehicle of  claim 26 , wherein the nanostructure comprises a gold nanoparticle. 
     
     
         28 . The in vivo agent delivery vehicle of  claim 26 , wherein the in vivo agent comprises a layer arranged about an exterior of the nanostructure. 
     
     
         29 . The in vivo agent delivery vehicle of  claim 26 , wherein the nanostructure comprises one or more internal voids and wherein the in vivo agent is contained at least partially within the one or more voids. 
     
     
         30 . The in vivo agent delivery vehicle of  claim 26 , wherein the in vivo agent comprises a therapeutic agent. 
     
     
         31 . The in vivo agent delivery vehicle of  claim 26 , wherein the in vivo agent comprises antibodies selected for tumor antigens. 
     
     
         32 . The in vivo agent delivery vehicle of  claim 26 , wherein bombardment by particle radiation induces decomposition of the outer coating so as to release the in vivo agent.