# US 9,433,800 B2 · Activatable particles, preparation and uses

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- Number: US 9,433,800 B2
- Document ID: US9433800B2
- Status: Granted
- Kind: B2
- Application number: 14/707,529
- Filed: 2015-05-08
- Published: 2015-08-27
- Granted: 2016-09-06
- Earliest claimed: 2004-05-10
- Assignees: Nanobiotix
- Applicants: Nanobiotix
- Inventors: Laurent Levy; Jean-Francois Hochepied; Jeremy Balencie; Paras Nath Prasad; Earl Jim Bergey; Edouard Andre Panak; Abdel Kader Boussaha
- Web page: https://patentgrep.com/patent/US9433800B2

## CPC

- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61K 41/0052: {Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy}
- A61K 49/0423: {Nanoparticles, nanobeads, nanospheres, nanocapsules, i.e. having a size or diameter smaller than 1 micrometer}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
- A61N 2005/0661: {ultraviolet}
- A61N 2005/1098: {Enhancing the effect of the particle by an injected agent or implanted device}
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention relates to novel activatable particles which can be used in the health sector. The invention more particularly relates to composite particles which can generate free radicals or heat when excited by X rays, and to the uses thereof in health, particularly human. The inventive particles comprise an inorganic-based, and optionally organic-based, nucleus and can be activated in vivo, in order to label or alter cells, tissues or organs. The invention also relates to methods for the production of said particles, and to pharmaceutical or diagnostic compositions containing same.

## Claims

### Claim 1

A method for inducing the lysis or destruction of cancer cells, in vitro, ex vivo or in vivo, comprising (i) contacting cancer cells with one or more biocompatible composite particles or nanoparticle aggregates which can generate free radicals or heat when excited by X rays applied by using a system of radiotherapy or radiography, each of said biocompatible composite particle comprising
a nucleus comprising a first inorganic compound that absorbs X rays and emits UV-visible energy, and said nucleus further comprising a second, inorganic or organic compound that absorbs said UV-visible energy and then produces said free radicals on contact with water or oxygen, said composite particle
optionally additionally comprising a biocompatible coating allowing the diffusion of small molecules and free radicals,
during a period of time sufficient to allow the particles or aggregates to penetrate inside the cancer cells and, (ii) exposing the cells to X rays, said exposure inducing the lysis or destruction of said cancer cells.

### Claim 2

A method of cancer treatment, comprising (i) administering biocompatible composite particles or nanoparticle aggregates, which can generate free radicals or heat when excited by X rays applied by using a system of radiotherapy or radiography, to a patient suffering from a cancer, each of said biocompatible composite particle comprising:
a nucleus comprising a first inorganic compound that absorbs X rays and emits UV-visible energy, and said nucleus further comprises a second, inorganic or organic compound, that absorbs said UV-visible energy and then produces said free radicals on contact with water or oxygen, said composite particle
optionally additionally comprising a biocompatible coating allowing the diffusion of small molecules and free radicals,
in conditions allowing the particles or nanoparticle aggregates to penetrate inside the cancer cells, and (ii) subsequently treating the patient in the presence of X rays, leading to an alteration, disturbance or functional destruction of the patient's cancer cells, thereby treating the cancer.

### Claim 3

A method of cancer treatment, comprising (i) administering a composition comprising biocompatible composite particles or nanoparticle aggregates, which can generate free radicals or heat when excited by X rays applied by using a system of radiotherapy or radiography, to a patient suffering from a cancer, each of said biocompatible composite particle comprising:
a nucleus comprising a first inorganic compound that absorbs X rays and emits UV-visible energy, and said nucleus further comprising a second, inorganic or organic compound, that absorbs said UV-visible energy and then produces said free radicals on contact with water or oxygen, said composite particle
optionally additionally comprising a biocompatible coating allowing diffusion of small molecules and free radicals,
in conditions allowing the particles or nanoparticle aggregates to penetrate inside the cancer cells, and (ii) subsequently treating the patient in the presence of X rays, leading to an alteration, disturbance or functional destruction of the patient's cancer cells, thereby treating the cancer.