Nanocarriers with multi-photon response elements
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.
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.