# US 2026/0076906 A1 · Nanoparticles for Enhancing Mitochondrial Networks

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- Number: US 2026/0076906 A1
- Document ID: US20260076906A1
- Status: Published application
- Kind: A1
- Application number: 19/172,228
- Filed: 2025-04-07
- Published: 2026-03-19
- Earliest claimed: 2024-04-05
- Assignees: Northeastern University
- Applicants: Northeastern University
- Inventors: Mansoor AMIJI; Lara Milane
- Web page: https://patentgrep.com/patent/US20260076906A1

## CPC

- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 38/46: Hydrolases (3)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12Y 306/05: acting on GTP; involved in cellular and subcellular movement (3.6.5)
- 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
- C12Y: ENZYMES

## Abstract

The present technology provides compositions and methods for enhancing mitochondrial networks in cells, particularly mammalian cells, and preferably human cells. The compositions and methods incorporate nanoparticles each including a mitochondrial network enhancing agent. When the nanoparticles are taken by the cell, the mitochondrial network enhancing agent binds to the mitofusin (MFN) proteins 1 and 2 thereby promoting fusion of mitochondria of the cell with one another and/or with endoplasmic reticulum of the cell. The present technology's compositions and methods find use in in the treatment of neurological, mitochondrial dysfunction, metabolic, and/or accelerated aging diseases or disorders including, for non-limiting examples, a progeroid syndrome, an MFN related disorder, Marie-Charcot Tooth disease, or any combination thereof.

## Claims

### Claim 1

A composition for enhancing a mitochondrial network in a cell, the composition comprising:
a plurality of nanoparticles each comprising a mitochondrial network enhancing agent;
wherein the mitochondrial network enhancing agent enhances the mitochondrial network of the cell when the nanoparticles are taken up by the cell.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the mitochondrial network enhancing agent binds to a mitofusin protein on mitochondria of the cell.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the mitofusin protein is mitofusin 1 (MFN1) or mitofusin 2 (MFN2).

### Claim 4 (depends on 3)

The composition of claim 3, wherein the mitofusin protein is MFN2.

### Claim 5 (depends on 3)

The composition of claim 3, wherein the mitochondrial network enhancing agent binds to MFN1 or MFN2 and thereby promotes fusion of mitochondria of the cell with one another and/or with endoplasmic reticulum of the cell.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the mitochondrial network enhancing agent is a peptide fragment of MFN1 or MFN2.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the mitochondrial network enhancing agent is a peptide fragment of MFN2 and comprises the amino acid sequence DIAEAVRLIMDSLHMAAR (SEQ ID NO:1), or a fragment or variant thereof having at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO:1.

### Claim 8 (depends on 7)

The composition of claim 7, wherein the mitochondrial network enhancing agent is a variant of SEQ ID NO: 1 comprising from 1 to 10, from 1 to 5, or from 1 to 3 conservative amino acid substitutions compared to SEQ ID NO:1.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the nanoparticles comprise lipid nanoparticles or biodegradable polymeric nanoparticles, and wherein the lipid nanoparticles or polymeric nanoparticles encapsulate the mitochondrial network enhancing agent.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the nanoparticles comprise lipid nanoparticles, and wherein the lipid nanoparticles are liposomes.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the liposomes are cationic liposomes.

### Claim 12 (depends on 11)

The composition of claim 11, wherein the cationic liposomes comprise 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the cationic lipid and further comprise one or more components selected from the group consisting of a neutral phospholipid, cholesterol, and a hydrophilic polymer such as polyethylene glycol (PEG).

### Claim 13 (depends on 11)

The composition of claim 11, wherein the cationic liposomes have a zeta potential greater than about +30 mV or less than about −30 mV.

### Claim 14 (depends on 9)

The composition of claim 9, wherein the nanoparticles are biodegradable polymeric nanoparticles.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the biodegradable polymeric nanoparticles comprise one or more biodegradable polymeric polymers selected from the group consisting of gelatin, chitosan, cellulose, cellulose derivatives, poly(ε-caprolactone) (PCL), polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolide, PEG-PLA diblock copolymer, PEG-PLGA diblock copolymer, PEG-PCL diblock copolymer, PCL-b-PEG-b-PCL co-polymer, polypropylene glycol (PPG), polyacrylic acid, polyacrylamide, poly(N-isopropylacrylamide), polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymer, hyaluronic acid, polyethylene oxide, polypropylene oxide, alginic acid, poly(betaaminoester) (PBAE), poly(glycolic acid) (PGA), and alginate.

### Claim 16 (depends on 1)

A method of enhancing a mitochondrial network in a cell of a mammalian subject, the method comprising:
(a) providing the composition of any of the claim 1; and
(b) administering the composition to the mammalian subject, whereby the mitochondrial network is enhanced in the cell of the mammalian subject.

### Claim 17 (depends on 16)

The method of claim 16, wherein said enhancing the mitochondrial network in the cell of the mammalian subject comprises enhancing fusion of mitochondria with other mitochondria and/or with endoplasmic reticulum in the cell, and/or increasing a size or density of the mitochondrial network in the cell.

### Claim 18 (depends on 16)

The method of claim 16, wherein said enhancing the mitochondrial network in the cell of the mammalian subject results in one or more of increased energy production, reduced reactive oxygen species (ROS) production, reduced nuclear DNA damage, reduced mitochondrial DNA damage, increased cell survival, increased protein folding efficiency, reduced protein misfolding, reduced accumulation of misfolded proteins, increased autophagy, increased mitophagy, and reduced apoptosis.

### Claim 19 (depends on 16)

The method of claim 16, wherein said enhancing the mitochondrial network in the cell of the mammalian subject comprises reducing fission of mitochondria in cells of the mammalian subject.

### Claim 20 (depends on 1)

A method of enhancing a mitochondrial network in a cell, the method comprising:
(a) providing the composition of claim 1 and a culture comprising the cell; and
(b) adding the composition to a medium of the culture, whereby nanoparticles of the composition are taken up by the cell and the mitochondrial network in the cell is enhanced.