Method and composition for hyperthermally treating cells

Patent metadata

Field	Value
Publication number	US-9302087-B2
Application number	US-201514679083-A
Country	US
Kind code	B2
Filing date	Apr 6, 2015
Priority date	Feb 14, 2002
Publication date	Apr 5, 2016
Grant date	Apr 5, 2016

Abstract

A method and composition for hyperthermally treating tumor cells in a patient under conditions that affect tumor stem cells and tumor cells.

First claim

What is claimed is:

1. A method of providing therapy to a patient in need thereof, the method comprising
administering to a patient in need thereof a complex comprising a plurality of nanoparticles and/or quantum dots associated with at least one aptamer targeting the nanoparticles and/or quantum dots to a site, under conditions sufficient to permit accumulation of the complex at the target site,
providing an energy source at the target site to penetrate the tissue and controllably heat the nanoparticles and/or quantum dots and generate thermal energy to induce a photoacoustic signal or sound wave from the nanoparticles and/or quantum dots,
using a processor to control the amount of thermal energy delivered at the desired temperature to the target site,
recording the temperature and photoacoustic signal or sound wave from the target site or from one or more multiple locations, and
amplifying and processing the recorded photoacoustic signal or sound waves to generate a computational tomographic image of the nanoparticles and/or quantum dots at the target site.

2. The method of claim 1 where the complex further comprises at least one agent selected from the group consisting of a medicament, a biologic, a gene, RNA, RNAi, siRNA, DNA, and combinations thereof, and comprises a thermosensitive polymer that releases the agent at the tissue target site when at attainment of a pre-defined temperature at the target site.

3. The method of claim 2 where the specific temperature to release the agent is in the range of 41° C. to 42° C. inclusive.

4. The method of claim 1 where the complex further comprises a photosensitizer to effect phototherapy in addition to hyperthermal therapy.

5. The method of claim 1 where the complex further comprises a radionuclide to effect radiotherapy in addition to hyperthermal therapy.

6. The method of claim 1 where the complex further comprises an immune stimulating agent to effect immunologic therapy in addition to hyperthermal therapy.

7. The method of claim 6 where the immune stimulating agent is selected from the group consisting of CHK1, CHK2, CHM1, and CHM2.

8. The method of claim 2 where the gene is an opsin family gene, the aptamer and nanoparticle and/or quantum dot complex containing the opsin family gene is administered to an excitable cell having a genetic defect in the opsin family gene and, upon energy stimulation, the opsin family gene administered to effect an action potential in the excitable cell membrane.

9. The method of claim 8 where the excitable cell is selected from the group consisting of a retinal cells, a brain cell, a spinal cord cell, a cardiac cell, and combinations thereof.

10. The method of claim 1 further comprising antibodies to target the nanoparticles and/or quantum dots to the tissue target site.

11. The method of claim 10 where the antibodies are selected from the group consisting of anti-beta amyloid, anti-Tau protein, and combinations thereof, the complex is injected locally into the cerebrospinal fluid or systemically, and the patient has Alzheimer's disease.

12. The method of claim 1 where the energy source is selected from the group consisting of electromagnetic radiation, ultrasound, radiofrequency waves, microwave energy, focused ultrasound, a magnetic field, a paramagnetic field, an alternating magnetic field, and combinations thereof.

13. The method of claim 1 where imaging generates a high-resolution two- or three-dimensional photoacoustic image that is optionally overlaid with another image produced simultaneously by a method selected from the group consisting of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), Raman spectroscopy, ultrasound, focused ultrasound, bioluminescence, optical fluorescence, functional MRI (fMRI), computed tomography (CT), positron emission tomography (PET), OCT, and alternating magnetic field imaging, molecular Imaging (MI), imaging using contrast agents, diffusion sensitive magnetic resonance imaging, and combinations thereof.

14. The method of claim 1 where hyperthermal therapy resulting in cell membrane damage is achievement of a temperature of at least one of 43° C.-45° C., greater than 42° C. up to 47° C., or greater than 42° C. up to 58° C.

15. The method of claim 1 where the medicament is an anti-vascular endothelial growth factor (anti-VEGF) agent and the patient has an ocular disease.

16. The method of claim 1 where the complex is coated or otherwise associated with biocompatible molecules selected from the group consisting of (poly)ethylene glycol (PEG), biotin, cell penetrating peptides (CPPs), ACPP, dendrimers, dendrimers conjugated with poly beta amine, small organic molecules, and combinations thereof.

17. The method of claim 2 where the complex comprises an at least partial coating of PEG at a thickness sufficient to minimize or prevent damage by plasma enzymes to DNA and/or RNA contained in the complex when the complex is administered non-locally.

18. The method of claim 1 provided to the patient in need thereof with a method for enhanced cell penetration of the aptamer-nanoparticle complex, the method selected from the group consisting of ultrasound, electroporation, and combinations thereof and resulting in therapy of cells at the target site while sparing normal cells.

19. The method of claim 1 where the complex is administered by local injection or systemic injection.

20. The method of claim 2 where the complex is administered by local injection at a site internal to a blood brain barrier, resulting in minimized plasma enzyme degradation of RNA and/or DNA contained in the complex.

Assignees

• Peyman Gholam A

Inventors

• Peyman Gholam A

Classifications

• A61N5/1001

  using radiation sources introduced into or applied onto the body; brachytherapy · CPC title

• A61B2090/3735

  Optical coherence tomography [OCT] · CPC title

• A61B2017/00106

  ultrasonic · CPC title

• A61N5/1017

  Treatment of the eye, e.g. for "macular degeneration" · CPC title

• A61K9/0009

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title