Mesoporous silica nanoparticles for diagnostic and therapeutic applications

Patent metadata

Field	Value
Publication number	US-11260127-B2
Application number	US-201816163211-A
Country	US
Kind code	B2
Filing date	Oct 17, 2018
Priority date	Oct 17, 2017
Publication date	Mar 1, 2022
Grant date	Mar 1, 2022

Abstract

A system for delivering a therapeutic agent to cell or tissue of a subject includes a mesoporous silica iron oxide nanoparticle with one or more therapeutic agents that are contained in a mesoporous silica layer of the nanoparticle and a remote radiofrequency (RF) energy source for applying RF energy to the nanoparticle effective to release the one or more therapeutic agents from the nanoparticle by mechanical tumbling and/or vibration of the nanoparticle, wherein release of the one or more therapeutic agents not caused by a hyperthermic response of the nanoparticle to the RF energy.

First claim

Having described the invention, we claim:

1. A system for delivering a therapeutic agent to cell or tissue of a subject, the system comprising:
a nanoparticle that includes an iron oxide core, a layer of mesoporous silica coated over and contiguous with the iron oxide core, and one or more therapeutic agents that are entirely contained in the mesoporous silica layer of the nanoparticle; and
a remote radiofrequency (RF) energy source for applying RF energy to the nanoparticle effective to release the one or more therapeutic agents from the mesoporous silica layer of the nanoparticle by mechanical tumbling and/or vibration of the nanoparticle, wherein release of the one or more therapeutic agents not caused by a hyperthermic response of the nanoparticle to the RF energy.

2. The system of claim 1 , the nanoparticle further comprising at least one targeting moiety.

3. The system of claim 2 , wherein the at least one targeting moiety is linked to the exterior surface of the mesoporous silica layer of the nanoparticle.

4. The system of claim 3 , including multiple targeting moieties, wherein the spacing and location of the targeting moieties on each nanoparticle is controlled to facilitate delivery, targeting, and/or therapeutic efficacy of the nanoparticle when administered to the subject.

5. The system of claim 1 , the nanoparticle having a diameter of about 50 nm to about 150 nm.

6. The system of claim 1 , the iron oxide core having a diameter of about 10 nm to about 50 nm.

7. The system of claim 1 , the therapeutic agent comprising an anti-cancer agent.

8. The system of claim 1 , the remote energy source being external to the subject.

9. The system of claim 1 , the RF energy effective to release the one or more therapeutic agents being less than that required to induce a localized temperature increase in the subject.

10. The system of claim 1 , wherein the RF energy is supplied at a frequency of about 1 kHz to about 50 kHz.

11. The system of claim 1 , further comprising one or more imaging agents contained in, and/or conjugated to the mesoporous silica layer of the nanoparticle.

12. The system of claim 1 , the one or more therapeutic agents comprising one or more anti-cancer agents.

13. The system of claim 11 , the nanoparticles being provided in a composition effective for intravenous delivery to the subject.

14. A method of treating cancer in a subject, the method comprising:
administering to the subject a plurality of nanoparticles, each nanoparticle including an iron oxide core, a layer of mesoporous silica coated over and contiguous with the iron oxide core, and one or more anti-cancer agents that are entirely contained in the mesoporous silica layer of the nanoparticle,
applying radiofrequency (RF) energy from a remote source external to the subject to the nanoparticles effective to release the one or more therapeutic agents from the mesoporous silica layer of the nanoparticles by mechanical tumbling and/or vibration of the nanoparticles, wherein release of the one or more therapeutic agents not caused by a hyperthermic response of the nanoparticles to the RF energy.

15. The method of claim 14 , the nanoparticle having a diameter of about 50 nm to about 150 nm and the iron oxide core having a diameter of about 10 nm to about 50 nm.

16. The method of claim 14 , the nanoparticle further comprising at least one targeting moiety that is linked to the exterior surface of the mesoporous silica layer of the nanoparticle.

17. The method of claim 14 , the nanoparticles being delivered intravenously to the subject and applying RF energy from the remote RF energy source to the administered nanoparticles localized to cancer cells of the cancer to release the one or more anti-cancer agents from the mesoporous silica layer of the nanoparticle.

18. The method of claim 14 , the RF energy effective to release the one or more anti-cancer agents being less than that required to induce a localized temperature increase in the subject.

19. The method of claim 14 , wherein the RF energy is applied at about 1 kHz to about 50 kHz.

20. The method of claim 14 , the one or more anti-cancer agents comprising one or more chemotherapeutic agents.

Assignees

• Univ Case Western Reserve

Inventors

• Karathanasis Efstathios
• Peiris Watuthentrige Pubudu M
• Perera Vindya
• Bauer Lisa

Classifications

• A61K47/6923

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

• A61P35/04

  specific for metastasis · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K41/0028 Primary

  Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title