# US 10,370,656 B2 · Nucleic acid functionalized nanoparticles for therapeutic applications

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- Number: US 10,370,656 B2
- Document ID: US10370656B2
- Status: Granted
- Kind: B2
- Application number: 15/296,387
- Filed: 2016-10-18
- Published: 2017-05-18
- Granted: 2019-08-06
- Earliest claimed: 2006-06-08
- Assignees: Northwestern University
- Applicants: Northwestern University
- Inventors: Chad A. Mirkin; David A. Giljohann; Dwight S. Seferos
- Web page: https://patentgrep.com/patent/US10370656B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/351: Conjugate
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Materials and methods for modulating cellular uptake of functionalized nanoparticles are provided. Also provided are materials and methods for modulating the effectiveness of a therapeutic agent with a functionalized nanoparticle.

## Claims

### Claim 1

A method of modulating effectiveness of an anticancer drug comprising the step of:
administering said anticancer drug concomitantly with an oligonucleotide-functionalized nanoparticle, wherein said oligonucleotide-functionalized nanoparticle comprises an oligonucleotide comprising a sequence that modulates the effectiveness of said anticancer drug, and wherein the nanoparticle does not comprise a targeting agent.

### Claim 2 (depends on 1)

The method of claim 1 wherein cellular localization of the anticancer drug is controlled by the oligonucleotide-functionalized nanoparticle.

### Claim 3 (depends on 1)

The method of claim 1 wherein the oligonucleotide sequence is a chemosensitizing antisense sequence.

### Claim 4 (depends on 3)

The method of claim 3 wherein the chemosensitizing antisense sequence increases the toxicity of the anticancer drug.

### Claim 5 (depends on 1)

The method of claim 1 wherein the nanoparticle is non-metallic.

### Claim 6 (depends on 1)

The method of claim 1 wherein the nanoparticle is metallic.

### Claim 7 (depends on 6)

The method of claim 6 wherein the nanoparticle comprises gold, silver, platinum, aluminum, palladium, copper, cobalt, indium, or nickel.

### Claim 8 (depends on 1)

The method of claim 1 wherein the effectiveness of the anticancer drug is altered by at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, at least 80%, at least 90%, at least 95%, at least 2-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold or more compared to effectiveness of the anticancer drug in the absence of the oligonucleotide-functionalized nanoparticle.

### Claim 9 (depends on 1)

The method of claim 1 wherein the oligonucleotide is from about 5 to about 100 nucleotides in length.

### Claim 10 (depends on 1)

The method of claim 1 wherein the nanoparticle is from about 5 nanometers (nm) to about 50 nm in mean diameter.

### Claim 11 (depends on 1)

The method of claim 1 wherein at least 20 oligonucleotides are functionalized to the nanoparticle.

### Claim 12 (depends on 1)

The method of claim 1 wherein density of oligonucleotide on the surface of the nanoparticle is from about 1.5 pmol/cm2 to about 25 pmol/cm2.

### Claim 13 (depends on 1)

The method of claim 1 wherein density of oligonucleotide on the surface of the nanoparticle is about 4 pmol/cm2.

### Claim 14 (depends on 1)

The method of claim 1 wherein the oligonucleotide is attached to the nanoparticle through a spacer.

### Claim 15 (depends on 1)

The method of claim 1 wherein the oligonucleotide is a DNA oligonucleotide or a RNA oligonucleotide.

### Claim 16 (depends on 1)

The method of claim 1 wherein the oligonucleotide-functionalized nanoparticle is associated with the anticancer drug.