Magnetic nanoscale particle compositions, and therapeutic methods related thereto

Abstract

Disclosed are thermotherapeutic compositions for treating disease material, and methods of targeted therapy utilizing such compositions. These compositions comprise a) stable single domain magnetic particles; b) magnetic nanoparticles comprising aggregates of superparamagnetic grains; or c) magnetic nanoparticles comprising aggregates of stable single magnetic domain crystals and superparamagnetic grains. These compositions may also comprise a radio isotope, potential radioactive isotope, chemotherapeutic agent. These methods comprise the administration to a patient's body, body part, body fluid, or tissue of bioprobes (energy susceptive materials attached to a target-specific ligand), and the application of energy to the bioprobes so as to destroy, rupture, or inactivate the target in the patient. Energy forms, such as AMF, are utilized to provide the energy. The disclosed methods may be useful in the treatment of a variety of indications, including cancers, diseases of the immune system, central nervous system and vascular system, and pathogen-borne diseases.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This is a Continuation-in-Part application claiming the benefit of and priority to Non-Provisional application having Ser. No. 10 / 200,082 filed on Jul. 19, 2002, and Provisional Patent Application having Ser. No. 60 / 307,785 filed on Jul. 25, 2001, both of which are incorporated herein by reference.TECHNICAL FIELD [0002] The present invention relates generally to targeted magnetic nanotherapy compositions and methods, and specifically, to magnetic nanoscale particle compositions that comprise an energy susceptive material that is attached to a target-specific ligand, and therapeutic methods that comprise the administration of such compositions to a patient's body, body part, tissue, or body fluid, and the administration of energy from an energy source, so as to destroy or inactivate the target. BACKGROUND [0003] The time between the onset of disease in a patient and the conclusion of a successful course of therapy is often unacceptably l...

AI Technical Summary

Benefits of technology

[0018] The biology of heat damage to cells is well understood, as is the clinical potential that a suitably targeted heating approach holds for the treatment of disease. This results from either the cytotoxic effect of heat, or the enhanced cytotoxic effect of radiation or chemotherapy resulting from heat sensitization of the cell when heat is combined with these treatments, or it can a combination of these. Heat applied to a cell in combination with ionizing radiation, such as ultraviolet, x-ray, gamma, beta, alpha, neutron, etc., or chemotherapy often results in an enhanced cytotoxic effect that may be significantly greater than expected from an additive combination of the ionizing energy or chemotherapy doses. Often, a cell will exhibit a high level of susceptibility to an otherwise sub-lethal dose of either chemotherapeutic agent or ionizing radiation when that dose is combined with heat, also at sub-lethal dose, in some combination. Such a combination therapy has a demonstrable significant clinical potential because damaging side effects from a dose of either heat or ionizing radiation may be avoided. Suitably targeting the combined form of treatment, i.e., in the bioprobes, thus has significant advantages over untargeted applications of either treatment modality or their combination.

[0019] In view of the above, there is a need for thermotherapeutic compositions for treating diseased tissue, pathogens, or other undesirable matter, that comprise a) stable single domain magnetic particles (characteristic relaxation time greater than 109 sec); b) magnetic nanoparticles comprising aggregates of superparamagnetic grains where the interacting magnetic moments create a collective state possessing characteristic relaxation times that are matched to the period of magnetic fields applied to a target within a patient's body; or c) magnetic nanoparticles comprising aggregates of stable single magnetic domain crystals and superparamagnetic grains, where the interactions of the stable single domain and superparamagnetic magnetic moments result in a collective state that increases the superparamagnetic characteristic relaxation time to a value much greater than 10−9 sec. It is also desirable to have hyperthermia-based treatment methods that incorporate selective delivery of such thermotherapeutic compositions, and that are safe and effective, short in duration, and require minimal invasion.

[0021] It is another object of the present invention to provide a method for treating disease material, that comprises selective delivery of such thermotherapeutic compositions, and that are safe and effective, short in duration, and require minimal invasion.

[0026] It is another object of the present invention to provide a composition and a treatment method that combine the benefits of hyperthermia, radiation, chemotherapy within the nanoparticle composition.

[0028] It is a further object of the present invention to provide methods for the treatment of tissue in a safe and effective manner, with minimal invasion, and short treatment periods.

[0029] The present invention pertains to thermotherapeutic magnetic compositions for treating disease material. In one embodiment, the composition comprises single-domain magnetic particles (characteristic relaxation time greater than 109 sec) attached to a target-specific ligand. In another embodiment, the composition comprises magnetic nanoparticles comprising aggregates of superparamagnetic grains, where the interacting magnetic moments create a collective state possessing characteristic relaxation times that are matched to the period of magnetic fields applied to a target within a patient's body. In another embodiment, the composition comprises magnetic nanoparticles comprising aggregates of stable single magnetic domain crystals and superparamagnetic grains, where the interactions of the stable single domain and superparamagnetic magnetic moments result in a collective state that increases the superparamagnetic characteristic relaxation time to a value much greater than 10−9 sec.

Problems solved by technology

However, a major problem with magnetic fluid hyperthermia has been the inability to selectively deliver a lethal dose of particles to the cells or pathogens of interest, particularly when the composition is limited to particles possessing characteristic relaxation times much shorter than the period of the applied RF.

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