Shielded Targeting Agents, Methods, and In Vivo Diagnostic System

Patent metadata

Field	Value
Publication number	US-2016129131-A1
Application number	US-201414539415-A
Country	US
Kind code	A1
Filing date	Nov 12, 2014
Priority date	Nov 12, 2014
Publication date	May 12, 2016
Grant date	—

Abstract

A system is provided which includes nanoparticle conjugates configured to bind with a tumor cell, the nanoparticle conjugate comprising a nanoparticle, at least one targeting entity bound to the nanoparticle, and at least one shielding entity that shields at the at least one targeting entity, the nanoparticle, or both; a body-mountable device mounted on an external surface of a living body and configured to detect a tumor cell binding response signal transmitted through the external surface, wherein the tumor cell binding response signal is related to binding of the nanoparticle conjugates with one or more tumor cells; and a processor configured to non-invasively detect the one or more tumor cells based on the tumor cell response signal. Nanoparticle conjugates and methods for use for treating or imaging tumor cells are also provided.

First claim

1 . A shielded nanoparticle conjugate comprising:
a nanoparticle; at least one targeting entity bound to the nanoparticle and configured to bind to tumor cells or tissue; and at least one shielding entity that shields the at least one targeting entity, the nanoparticle, or both.

2 . The conjugate of claim 1 , wherein the nanoparticle comprises a polymer material.

3 . The conjugate of claim 1 , wherein the nanoparticle comprises a non-polymeric material.

4 . The conjugate of claim 1 , wherein the nanoparticle comprises a magnetic or paramagnetic material.

5 . The conjugate of claim 1 , wherein the targeting entity comprises an antibody, peptide, protein, nucleic acid, small molecule, carbohydrate, or lipid.

6 . The conjugate of claim 1 , wherein the shielding entity is a pH-sensitive polymer, an idiopathic aptamer directed to a tumor metabolite, or a protease-sensitive bivalent peptide.

7 . The conjugate of claim 1 , wherein the targeting entity is an antibody and the shielding entity is a protease-sensitive bivalent peptide that binds to the antigen binding site of the antibody.

8 . The conjugate of claim 1 , wherein the targeting entity is an antibody and the shielding entity is a pH-sensitive polymer that degrades in an acidic tumor microenvironment.

9 . The conjugate of claim 1 , wherein the targeting entity is an antibody and the shielding entity is a bivalent anti-idiotypic aptamer with a tumor metabolite-binding domain, wherein the aptamer binds to the antigen binding site of the antibody.

10 . The conjugate of claim 1 , further comprising at least one detection label.

11 . The conjugate of claim 1 , further comprising at least one agent to be delivered to the tumor cells.

12 . The conjugate of claim 11 , wherein the agent comprises at least one anti-tumor agent.

13 . The conjugate of claim 11 , wherein the agent comprises a contrast imaging agent.

14 . The conjugate of claim 1 , wherein said conjugate comprises at least one moiety that exhibits fluorescence, luminescence, magnetic or paramagnetic properties.

15 . A method for in vivo imaging in a mammal of tumor cells or tissue that express a selected marker; said method comprising the steps of:
(a) administering to the mammal a composition as recited in claim 1 , wherein the targeting entity is specific for the selected marker; (b) waiting a time sufficient to allow the targeting entity to bind to the selected markers of the tumor cells or tissue; and (c) imaging the cells or tissue with a non-invasive imaging technique that has a resolution enhanced by the presence of the conjugate on or within the cells or tissue.

16 . The method of claim 15 , wherein the imaging technique is selected from the group consisting of magnetic resonance imaging (MRI), magnetic spectroscopy, X-ray, positron emission tomography (PET), computer tomography (CT), ultrasonic imaging, and optical imaging.

17 . A method for killing or inhibiting the growth of tumor cells or tissue in a mammal, said method comprising administering an effective amount of the nanoparticle conjugate of claim 1 to said mammal, wherein the targeting entity is specific for a marker that is specifically expressed by the tumor cells or tissue.

18 . The method of claim 17 , further comprising the step of imaging the cells or tissue with a non-invasive imaging technique that has a resolution enhanced by the presence of the conjugate on or within the cells.

19 . A system comprising:
a plurality of nanoparticle conjugates, each nanoparticle conjugate comprising a nanoparticle, at least one targeting entity bound to the nanoparticle and configured to bind with a tumor cell, and at least one shielding entity that shields the at least one targeting entity, the nanoparticle, or both; a body-mountable device, wherein the body-mountable device is mountable on an external surface of a living body and configured to detect a tumor cell binding response signal transmitted through the external surface of the living body, wherein the tumor cell binding response signal is related to binding of the nanoparticle conjugates with one or more tumor cells; and a processor configured to non-invasively detect the one or more tumor cells based on the tumor cell response signal.

20 . The system of claim 19 , wherein the body-mountable device comprises a detector for detecting the tumor cell response signal.

21 . The system of claim 19 , further comprising a modulation source configured to modulate the tumor cell response signal differently than a background signal.

22 . The system of claim 21 , wherein the body-mountable device includes the modulation source.

23 . The system of claim 21 , wherein the processor is configured to differentiate the tumor cell response signal from the background signal based, at least in part, on the modulation by the modulation source.

24 . The system of claim 21 , further comprising an interrogating signal source, the tumor cell response signal being transmitted in response to the interrogating signal.

25 . The system of claim 24 , wherein the modulation source is configured to modulate the tumor cell response signal by modulating the interrogating signal source.

26 . A method comprising:
introducing a plurality of nanoparticle conjugates into an environment, each nanoparticle conjugate comprising a nanoparticle, at least one targeting entity bound to the nanoparticle and configured to bind with a tumor cell, and at least one shielding entity configured to shield the nanoparticle, the at least one targeting entity, or both; detecting a response signal transmitted from the environment, wherein the response signal includes a tumor cell response signal that is related to binding of the nanoparticle conjugates to tumor cells and wherein the response signal is modulated; and detecting one or more tumor cells by differentiating the response signal from a background signal, at least in part, based on the modulation.

Assignees

• Google Inc

Inventors

• Vitari Alberto Clemente
• Klein Joshua Simon
• Schwartz Jerrod Joseph
• Homyk Andrew
• Pavlovic Marija

Classifications

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title

• A61B5/0515

  Magnetic particle imaging · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title