Triplet-triplet annihilation upconversion system, and compositions and methods thereof for drug delivery

Patent metadata

Field	Value
Publication number	US-11078217-B2
Application number	US-201816641559-A
Country	US
Kind code	B2
Filing date	Sep 2, 2018
Priority date	Sep 5, 2017
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The invention provides a novel class of materials that possess triplet-triplet annihilation upconversion, compositions and methods of preparation and use thereof. The invention also relates to use of such materials and nanoparticles, for example, in stimulus-responsive, in situ delivery of biologically active agents.

First claim

The invention claimed is:

1. An upconversion composition, comprising an organic triplet photosensitizer molecule and an organic emitter molecule, wherein the composition is characterized by an upconversion upon excitation in the red region of about 500 nm to about 600 nm or far red region of about 600 nm to about 700 nm with an emission in the deep blue region of about 410 nm to about 550 nm, wherein each of the triplet photosensitizer and emitter molecules comprises no metallic elements, wherein the triplet photosensitizer molecule has the structural formula (I):

wherein
each of R 1 and R 2 is independently selected from the group consisting of: H, bromo, iodio, alkynyl, alkyl, alkenyl, azide, PEG, amino, carboxyl acid and hydroxyl;
R 3 is selected from the group consisting of: bromo and iodio;
R 4 is an arylethynyl group; and
each R 5 is independently selected from the group consisting of: H and alkyl.

2. The composition of claim 1 , wherein the emitter molecule is 9-phenylacetylene anthracene or a derivative thereof.

3. The composition of claim 2 , wherein R 4 is selected from the group consisting of: phenylethynyl, naphthalene ethynyl, carbazole ethynyl and fluorenyl ethynyl.

4. The composition of claim 3 , wherein R 4 is selected from the group consisting of:

wherein each R 6 is independently a C 2 -C 16 alkyl group.

5. A compound having the structural formula (I):

wherein
each of R 1 and R 2 is independently selected from the group consisting of: H, bromo, iodio, alkynyl, alkyl, alkenyl, azide, PEG, amino, carboxyl acid and hydroxyl;
R 3 is selected from the group consisting of: bromo and iodio;
R 4 is an arylethynyl group; and
each R 5 is independently selected from the group consisting of: H and alkyl.

6. A biocompatible nanoparticle delivery system, comprising:
a triplet photosensitizer molecule and an emitter molecule, wherein
each of the triplet photosensitizer and emitter molecules is an organic molecule and comprises no metallic elements;
the triplet photosensitizer is excited by a light in the red region of about 500 nm to about 600 nm or far red region of about 600 nm to about 700 nm causing an emission by the emitter molecule in the deep blue region of about 410 nm to about 550 nm; and
a photolabile molecule comprising a biologically active agent, wherein the biologically active agent is releasable upon absorption of the emission by the emitter molecule, wherein the triplet photosensitizer molecule has the structural formula (I):

wherein
each of R 1 and R 2 is independently selected from the group consisting of: H, bromo, iodio, alkynyl, alkyl, alkenyl, azide, PEG, amino, carboxyl acid and hydroxyl;
R 3 is selected from the group consisting of: bromo and iodio;
R 4 is an arylethynyl group; and
each R 5 is independently selected from the group consisting of: H and alkyl.

7. The nanoparticle delivery system of claim 6 , wherein the nanoparticle is characterized by a core-shell structure, wherein the triplet photosensitizer molecule and an emitter molecule are deposed in the core whereas the photolabile molecule is deposed in the shell.

8. The nanoparticle delivery system of claim 6 , wherein the emitter molecule is 9-phenylacetylene anthracene.

9. The nanoparticle delivery system of claim 8 , wherein R 4 is selected from the group consisting of: phenylethynyl, naphthalene ethynyl, carbazole ethynyl and fluorenyl ethynyl.

10. The nanoparticle delivery system of claim 9 , wherein R 4 is selected from the group consisting of:

wherein each R 6 is independently a C 2 -C 16 alkyl group.

11. The nanoparticle delivery system of claim 6 , wherein the biologically active agent is an anti-cancer agent.

12. The nanoparticle delivery system of claim 6 , wherein the photolabile molecule comprises a coumarin moiety.

13. The nanoparticle delivery system of claim 11 , wherein the anti-cancer agent is chlorambucil.

14. A pharmaceutical composition comprising a nanoparticle delivery system of claim 6 .

15. The compound of claim 5 , wherein R 4 is selected from the group consisting of: phenylethynyl, naphthalene ethynyl, carbazole ethynyl and fluorenyl ethynyl.

16. The compound of claim 15 , wherein R 4 is selected from the group consisting of:

wherein each R 6 is independently a C 2 -C 16 alkyl group.

17. The compound of claim 16 , wherein each of R 1 and R 2 is H, R 3 is I, R 4 is a substituted or unsubstituted fluorenyl ethynyl, and each R 5 is methyl.

Assignees

• Univ Massachusetts

Inventors

• Han Gang
• Huang Ling

Classifications

• C09B23/04

  one >CH- group, e.g. cyanines, isocyanines, pseudocyanines · CPC title

• C09B57/00

  Other synthetic dyes of known constitution · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K47/558

  the modifying agent being a chemiluminescent acceptor · CPC title

• A61K47/6923

  the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb · CPC title