Described herein are systems and methods for employing a tumor targeted cerium oxide nanoparticle system, T-CeNP, for cancer therapy to hinder cancer associated fibroblast (CAF) transdifferentiation and reprogram CAFs back to normal fibroblasts to reduce tumor size and prevent metastasis.

A process for making nanoparticles of biocompatible materials is described, wherein an aqueous reaction mixture comprising cerous ion, ethylenediaminedisuccinic acid, an oxidant, water, and optionally citric acid, is provided along with temperature conditions to directly form within the reaction mixture, a stable dispersion of cerium oxide nanoparticles. Biocompatible nanoparticles comprised of cerium oxide, ethylenediaminedisuccinic acid, and optionally citric acid, are described. An increase in catalase-like enzyme activity is demonstrated by cerium oxide nanoparticles prepared with citric acid and ethylenediaminedisuccinic acid.

A process for making nanoparticles of biocompatible materials is described, wherein an aqueous reaction mixture comprising cerous ion, ethylenediaminedisuccinic acid, an oxidant, water, and optionally citric acid, is provided along with temperature conditions to directly form within the reaction mixture, a stable dispersion of cerium oxide nanoparticles. Biocompatible nanoparticles comprised of cerium oxide, ethylenediaminedisuccinic acid, and optionally citric acid, are described. An increase in catalase-like enzyme activity is demonstrated by cerium oxide nanoparticles prepared with citric acid and ethylenediaminedisuccinic acid.

Methods for treating tumors by administering FLASH radiation and a therapeutic agent to a patient with cancer are disclosed. The methods provide the dual benefits of anti-tumor efficacy plus normal tissue protection when combining therapeutic agents with FLASH radiation to treat cancer patients. The methods described herein also allow for the classification of patients into groups for receiving optimized radiation treatment in combination with a therapeutic agent based on patient-specific biomarker signatures. Also provided are radiation treatment planning methods and systems incorporating FLASH radiation and therapeutic agents.

Methods for treating tumors by administering FLASH radiation and a therapeutic agent to a patient with cancer are disclosed. The methods provide the dual benefits of anti-tumor efficacy plus normal tissue protection when combining therapeutic agents with FLASH radiation to treat cancer patients. The methods described herein also allow for the classification of patients into groups for receiving optimized radiation treatment in combination with a therapeutic agent based on patient-specific biomarker signatures. Also provided are radiation treatment planning methods and systems incorporating FLASH radiation and therapeutic agents.

In various embodiments, methods of treating a cancer are provided. In certain embodiments, the methods comprise administering to a mammal in need thereof i) one or more checkpoint inhibitor(s); and ii) one or more camptothecin analogs, and, optionally, or one or more autophagy inhibitors wherein said camptothecin analog, and one or more autophagy inhibitors, when present, are provided inside a delivery vehicle where said delivery vehicle comprises: a nanoparticle comprising one or more cavities disposed within said nanoparticle and an outside surface where said one or more cavities are in fluid communication the outside surface of said nanoparticle; said one or more camptothecin analog, one or more autophagy inhibitors, when present, are disposed within said one or more cavities; and a lipid bilayer is disposed on the surface of said nanoparticle where said lipid bilayer fully encapsulates the nanoparticle.

In various embodiments, methods of treating a cancer are provided. In certain embodiments, the methods comprise administering to a mammal in need thereof i) one or more checkpoint inhibitor(s); and ii) one or more camptothecin analogs, and, optionally, or one or more autophagy inhibitors wherein said camptothecin analog, and one or more autophagy inhibitors, when present, are provided inside a delivery vehicle where said delivery vehicle comprises: a nanoparticle comprising one or more cavities disposed within said nanoparticle and an outside surface where said one or more cavities are in fluid communication the outside surface of said nanoparticle; said one or more camptothecin analog, one or more autophagy inhibitors, when present, are disposed within said one or more cavities; and a lipid bilayer is disposed on the surface of said nanoparticle where said lipid bilayer fully encapsulates the nanoparticle.

The presently disclosed subject matter provides agents, compositions, and methods for augmenting ablation of a target tissue in a subject in need thereof, for example, using agents that modulate protective and/or reparative cellular processes induced in target tissue by application of ablative energy to the target tissue to sensitize the target tissue to the ablative energy. The presently disclosed subject matter further provides methods for augmenting radiofrequency ablation of cardiac tissue, for example, by applying radiofrequency energy to ablate cardiac tissue in the presence of metallic nanoparticles magnetically guided to the cardiac tissue.

The presently disclosed subject matter provides agents, compositions, and methods for augmenting ablation of a target tissue in a subject in need thereof, for example, using agents that modulate protective and/or reparative cellular processes induced in target tissue by application of ablative energy to the target tissue to sensitize the target tissue to the ablative energy. The presently disclosed subject matter further provides methods for augmenting radiofrequency ablation of cardiac tissue, for example, by applying radiofrequency energy to ablate cardiac tissue in the presence of metallic nanoparticles magnetically guided to the cardiac tissue.

Disclosed herein are anti-lymphocyte antigen 6 complex, locus H (LY6H) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.