Nanocarriers with multi-photon response elements

Patent metadata

Field	Value
Publication number	US-9724417-B2
Application number	US-201414455613-A
Country	US
Kind code	B2
Filing date	Aug 8, 2014
Priority date	Sep 23, 2009
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

Compositions are provided in which dendrimers and/or nanoparticles are synthesized with multi-photon responsive elements and self-immolative oligomers. The compositions may be utilized to selectively deliver Payloads within tissue by irradiating the compositions. The compositions may also be used to amplify sensitivity to irradiation.

First claim

The invention claimed is:

1. A method for delivering a Payload to a tissue comprising the steps of:
synthesizing a particle comprising polymer strands and a crosslinker to form a molecular network that encapsulates the Payload, wherein said crosslinker comprises a multi-photon responsive element covalently linked to a self-immolative backbone subunit comprising the structure

where “PG” denotes a protecting group;
administering said particle to said tissue; and
irradiating said tissue comprising said particle with electromagnetic radiation;
wherein said particle is disrupted in situ following absorption of said electromagnetic radiation.

2. The method of claim 1 , wherein said electromagnetic radiation is near infrared red light or ultraviolet light.

3. The method of claim 1 , wherein said method provides an amplified response to said electromagnetic radiation.

4. The method of claim 1 , wherein said Payload comprises a pharmaceutical agent, stem cell differentiation agents, immunogens or antibodies.

5. The method of claim 1 , wherein said multi-photon responsive element is a two-photon responsive element.

6. The method of claim 1 , wherein said multi-photon responsive unit is a bromo-coumarin group.

7. The method of claim 1 , wherein said molecular network comprises acrylamide polymers.

8. The method of claim 1 , wherein said molecular network comprises PEG polymers.

9. The method of claim 1 , wherein said self-immolative backbone subunit is a self-immolative dendrimer oligomer.

10. The method of claim 1 , wherein said multi-photon responsive unit comprises the structure

11. A method for delivering a Payload to a target tissue comprising:
encapsulating the Payload within a plurality of nanocarriers, each nanocarrier comprising a molecular cage synthesized by cross-linking polymer strands with a multi-photon responsive element covalently linked to a self-immolative backbone subunit comprising the structure

where “PG” denotes a protecting group;
administering said plurality of nanocarriers to said target tissue; and
irradiating said target tissue and the plurality of nanocarriers with electromagnetic radiation;
wherein said molecular cage unravels and releases the Payload in situ following absorption of said electromagnetic radiation.

12. The method of claim 11 , wherein said electromagnetic radiation is near infrared red light or ultraviolet light.

13. The method of claim 11 , wherein said Payload comprises a pharmaceutical agent, stem cell differentiation agents, immunogens or antibodies.

14. The method of claim 11 , wherein said multi-photon responsive element is a two-photon responsive element.

15. The method of claim 11 , wherein said polymer strands comprise polyacrylamide polymers.

16. A method for delivering a Payload to a target tissue comprising:
encapsulating the Payload within a molecular network comprising strands of polymer crosslinked by a crosslinker to form a carrier that mechanically encapsulates the Payload, the crosslinker comprising a dual-photon responsive element covalently linked to a self-immolative backbone subunit comprising the structure

where “PG” denotes a protecting group;
administering a plurality of said carriers to said target tissue; and
irradiating said target tissue and said carriers with a dual-photon trigger;
wherein, upon exposure to the dual-photon trigger, the crosslinker cleaves to unravel the strands and release the Payload in situ.

17. The method of claim 16 , wherein said electromagnetic radiation is near infrared red light or ultraviolet light.

18. The method of claim 16 , wherein said Payload comprises a pharmaceutical agent, stem cell differentiation agents, immunogens or antibodies.

Assignees

• Univ California

Inventors

• Almutairi Adah
• Fomina Nadezda
• Sankaranarayanan Jagadis

Classifications

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• C08G63/06

  derived from hydroxycarboxylic acids · CPC title

• A61K2039/622

  non-covalent binding · CPC title

• A61K9/5138

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title