Radiofrequency-induced synchronization of in situ hyperthermia and chemotherapy via magnetic-nanoconjugates

Patent metadata

Field	Value
Publication number	US-9351941-B2
Application number	US-201313905177-A
Country	US
Kind code	B2
Filing date	May 30, 2013
Priority date	May 30, 2012
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The present invention relates to a magnetic nanoparticle for tumor therapy, comprising: a magnetic core; a shell encapsulating a surface of the magnetic core, wherein the shell is made of a polymer with carboxylic groups; a poly-nucleotide chain connected to a surface of the shell; an anti-tumor drug connected to the poly-nucleotide chain, wherein the anti-tumor drug comprises at least one functional group, and each of the functional group is independently a pyrimidine group or a purine group; and an antibody connected to the shell, wherein the antibody identifies a target tumor. In addition, the present invention further provides a method for manufacturing the magnetic nanoparticles for tumor therapy and a pharmaceutical composition containing the magnetic nanoparticles. Accordingly, the magnetic nanoparticle for tumor therapy of the present invention can achieve effective treatment of tumor by synergistic effects between hyperthermia and targeted chemotherapy.

First claim

What is claimed is:

1. A magnetic nanoparticle for tumor therapy, comprising:
a magnetic core;
a shell fully encapsulating a surface of the magnetic core, wherein the shell is made of a polymer with carboxylic groups;
a poly-nucleotide chain connected to a surface of the shell, wherein the poly-nucleotide chain is a poly-adenine chain with an aminated end, and the poly-adenine chain connects to the surface of the shell via the aminated end of the poly-adenine chain;
an anti-tumor drug connected to the poly-nucleotide chain, wherein the anti-tumor drug comprises at least one functional group, and each of the functional group is independently a pyrimidine group or a purine group; and
an antibody connected to the shell through a hydrophilic polymer chain, wherein the antibody identifies a target tumor, and the hydrophilic polymer chain contains amines on its two ends, wherein the amine on one end connects the carboxylic groups of the shell, and the amine on the other end connects the antibody;
wherein the anti-tumor drug is employed to perform tumor growth inhibition or modulation of tumor microenvironment, and
wherein a local radio frequency is provided for inducing hyperthermia during the treatment of the magnetic nanoparticle for tumor therapy, and
wherein the induced hyperthermia will synchronize the triggered release of anti-tumor modalities and thereby enhance the therapeutic efficacy through synergistic activity.

2. The magnetic nanoparticle of claim 1 , wherein the magnetic core is made of a material selected from the group consisting of Fe, Fe 3 O 4 , Fe 2 O 3 , Pt, Ni, and a combination thereof.

3. The magnetic nanoparticle of claim 1 , wherein the magnetic core has an average particle diameter of 5-100 nm.

4. The magnetic nanoparticle of claim 1 , wherein the shell is made of poly(acrylic acid), poly(styrene-alt-maleic acid), or a combination thereof.

5. The magnetic nanoparticle of claim 1 , wherein the shell is made of poly(styrene-alt-maleic acid).

6. The magnetic nanoparticle of claim 1 , wherein the anti-tumor drug is 5-fluorouracil, arabinosylcytosine, capecitabine, gemcitabine, or a combination thereof.

7. The magnetic nanoparticle of claim 1 , wherein the anti-tumor drug is 5-fluorouracil.

8. The magnetic nanoparticle of claim 1 , wherein the anti-tumor drug has a release rate of 80-100% at 40-50° C.

9. A method for manufacturing a magnetic nanoparticle for tumor therapy, comprising the steps of:
providing a magnetic core;
forming a shell fully encapsulating a surface of the magnetic core, wherein the shell is made of a polymer with carboxylic groups;
forming at least one poly-nucleotide chain on the shell, wherein the poly-nucleotide chain is formed on the shell in a solution comprising dimethylformide (DMF), and the poly-nucleotide chain is a poly-adenine chain with an aminated end;
forming at least one anti-tumor drug on the poly-nucleotide chain, wherein the anti-tumor drug comprises at least one functional group, and each of the functional group is independently a pyrimidine group or a purine group; and
forming at least one antibody on the shell through a hydrophilic polymer chain, wherein the antibody identifies a target tumor, and the hydrophilic polymer chain contains amines on its two ends, wherein the amine on one end connects the carboxylic groups of the shell, and the amine on the other end connects the antibody;
wherein the anti-tumor drug is employed to perform tumor growth inhibition or modulation of tumor microenvironment, and
wherein a local radio frequency is provided for inducing hyperthermia during the treatment of the magnetic nanoparticle for tumor therapy,
wherein the induced hyperthermia will synchronize the triggered release of anti-tumor modalities and thereby enhance the therapeutic efficacy through synergistic activity.

10. The method of claim 9 , wherein the magnetic core is made of a material selected from the group consisting of Fe, Fe 3 O 4 , Fe 2 O 3 , Pt, Ni, or a combination thereof.

11. The method of claim 9 , wherein the magnetic core has an average particle diameter of 5-100 nm.

12. The method of claim 9 , wherein the shell is made of poly(acrylic acid), poly(styrene-alt-maleic acid), or a combination thereof.

13. The method of claim 9 , wherein the anti-tumor drug is 5-fluorouracil, arabinosylcytosine, capecitabine, gemcitabine, or a combination thereof.

14. A pharmaceutical composition for tumor therapy, comprising:
an effective amount of a magnetic nanoparticle for tumor therapy, which comprises:
a magnetic core;
a shell fully encapsulating a surface of the magnetic core, wherein the shell is made of a polymer with carboxylic groups;
a poly-nucleotide chain connected to a surface of the shell, wherein the poly-nucleotide chain is a poly-adenine chain with an aminated end, and the poly-adenine chain connects to the surface of the shell via the aminated end of the poly-adenine chain;
an anti-tumor drug connected to the poly-nucleotide chain, wherein the anti-tumor drug comprises at least one functional group, and each of the functional group is independently a pyrimidine group or a purine group; and
an antibody connected to the shell through a hydrophilic polymer chain, wherein the antibody identifies a target tumor, and the hydrophilic polymer chain contains amines on its two ends, wherein the amine on one end connects the carboxylic groups of the shell, and the amine on the other end connects the antibody; and
a pharmaceutical acceptable carrier;
wherein the anti-tumor drug is employed to perform tumor growth inhibition or modulation of tumor microenvironment, and
wherein a local radio frequency is provided for inducing hyperthermia during the treatment of the magnetic nanoparticle for tumor therapy
wherein the induced hyperthermia will synchronize the triggered release of anti-tumor modalities and thereby enhance the therapeutic efficacy through synergistic activity.

15. The pharmaceutical composition of claim 14 , wherein the pharmaceutically acceptable carrier is at least one selected from a group consisting of:
active agents, adjuvant agents, dispersion agents, wetting agents, and suspension agents.

16. The pharmaceutical composition of claim 14 , wherein the magnetic core is made of a material selected from the group consisting of Fe, Fe 3 O 4 , Fe 2 O 3 , Pt, Ni, or a combination thereof.

17. The pharmaceutical composition of claim 14 , wherein the magnetic core has an average particle diameter of 5˜100 nm.

18. The pharmaceutical composition of claim 14 , wherein the shell is made of poly(acrylic acid), poly(styrene-alt-maleic acid), or a combination thereof.

19. The pharmaceutical composition of claim 14 , wherein the anti-tumor drug is 5-fluorouracil, arabinosylcytosine, capecitabine, gemcitabine, or a combination thereof.

20. The magnetic nanoparticle of claim 1 , wherein the magnetic core is Fe 3 O 4 ; the anti-tumor drug is 5-fluorouracil; and the antibody is anti-Her2.

Assignees

• Univ Nat Cheng Kung

Inventors

• Shieh Dar-Bin
• Yeh Chen-Sheng
• Li Tsung-Ju
• Huang Chih-Chia

Classifications

• A61K47/48569

  Human Necessities · mapped topic

• A61K47/48861

  Human Necessities · mapped topic

• A61K9/5169 Primary

  Proteins, e.g. albumin, gelatin · CPC title

• A61K47/6851 Primary

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

• A61K47/6923

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