# US 10,369,221 B2 · Conjugated porphyrin carbon quantum dots for targeted photodynamic therapy

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- Number: US 10,369,221 B2
- Document ID: US10369221B2
- Status: Granted
- Kind: B2
- Application number: 15/806,514
- Filed: 2017-11-08
- Published: 2018-05-10
- Granted: 2019-08-06
- Earliest claimed: 2016-11-08
- Assignees: Hong Kong Baptist University
- Applicants: Hong Kong Baptist University
- Inventors: Xunjin Zhu; Wai Kwok Wong; Fengshou Wu
- Web page: https://patentgrep.com/patent/US10369221B2

## CPC

- A61K 41/0071: {PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6857: {the tumour determinant being from lung cancer cell}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- G01N 33/5752: of the lungs
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- G01N 33/582: {with fluorescent label}
- G01N 33/587: {Nanoparticles}
- G01N 2333/71: for growth factors; for growth regulators
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure relates to porphyrin containing carbon quantum dots useful for bioimaging and/or phytodynamic therapy.

## Claims

### Claim 1

A nanoparticle comprising a carbon matrix and one or more moieties present on the surface of the carbon matrix, wherein the one or more moieties is selected from the group consisting of —CO2H and —C(═O)NH(CH2CH2O)nCH2CH2NHR, wherein n is a whole number selected from 3-100 and R is a hydrogen or a targeting group; and the carbon matrix comprises a compound of Formula I:
wherein, M is a metal selected from the group consisting of Co, Ni, Mn, Zn, Pt, and Pd;
or M represents two hydrogen, each of which is covalently bound to a nitrogen; and
represents a covalent nitrogen-carbon bond between the compound of Formula I and the carbon matrix.

### Claim 2 (depends on 1)

The nanoparticle of claim 1, wherein n is a whole number selected from 3-40.

### Claim 3 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has an average diameter of about 3 to about 3.5 nm.

### Claim 4 (depends on 1)

The nanoparticle of claim 1, wherein the carbon matrix comprises graphitic carbon.

### Claim 5 (depends on 1)

The nanoparticle of claim 1, wherein the targeting group is selected from the group consisting of an antibody, an antibody fragment, a peptide, an aptamer, and a small molecule.

### Claim 6 (depends on 5)

The nanoparticle of claim 5, wherein the antibody is cetuximab or panitumumab; the peptide is a cyclic RGD peptide; and the aptamer is anti-nucleolin aptamer AS1411.

### Claim 7 (depends on 1)

The nanoparticle of claim 1, wherein the nanoparticle has an average diameter of about 3 to about 3.5 nm; n is whole number selected from 3-40; the carbon matrix comprises graphitic carbon; M is Zn; or M represents two hydrogen, each of which is covalently bound to a nitrogen; and R is cetuximab.

### Claim 8 (depends on 7)

A method for treating non-small cell lung cancer in a patient in need thereof, comprising the step of administering a therapeutically effective amount of the nanoparticle of claim 7 to the patent.

### Claim 9 (depends on 7)

A method for imaging a cell that overexpresses epidermal growth factor receptor (EGFR), comprising the step of contacting the cell with the nanoparticle of claim 7 and detecting the fluorescence of the nanoparticle of claim 7.

### Claim 10 (depends on 1)

A method of synthesizing the nanoparticle of claim 1, comprising the steps of:
a) contacting an organic acid selected from the group consisting of aspartic acid, citric acid, ethylenediaminetetraacetic acid (EDTA), glutamic acid, and tartaric acid with a compound of Formula II:
wherein, M is a metal selected from the group consisting of Co, Ni, Mn, Zn, Pt, and Pd; or M represents two hydrogen, each of which is covalently bound to a nitrogen; thereby forming a polymerized polyamide;
b) subjecting the polymerized polyamide to hydrothermal carbonization thereby forming an unfunctionalized nanoparticle comprising a carbon matrix and one or more —CO2H present on the surface of the carbon matrix; and the carbon matrix comprises a compound of Formula I:
wherein, M is a metal selected from the group consisting of Co, Ni, Mn, Zn, Pt, and Pd; or M represents two hydrogen, each of which is covalently bound to a nitrogen; and
represents a covalent nitrogen-carbon bond between the compound of Formula I and the carbon matrix;
c) contacting the unfunctionalized nanoparticle with NH2(CH2CH2O)nCH2CH2NH2, wherein n is a whole number selected from 3-100, under conditions for forming an amide bond, thereby forming an amine terminated nanoparticle; and
d) optionally contacting the amine terminated nanoparticle with a targeting group comprising an activated carbonyl thereby forming the nanoparticle of claim 1.

### Claim 11 (depends on 10)

The method of claim 10, wherein the step of contacting the compound of Formula II and the organic acid, the compound of Formula II and organic acid are present in a mass to mass ratio of about 1:10 to about 5:15 of the compound of Formula II to the organic acid.

### Claim 12 (depends on 10)

The method of claim 10, wherein the organic acid is citric acid.

### Claim 13 (depends on 10)

The method of claim 10, wherein n is a whole number selected from 3-40.

### Claim 14 (depends on 13)

The method of claim 13, wherein the step of contacting the contacting the unfunctionalized nanoparticle with NH2(CH2CH2O)nCH2CH2NH2, the unfunctionalized nanoparticle and NH2(CH2CH2O)nCH2CH2NH2 are present in a mass to mass ratio of about 1:4 to about 5:95 the unfunctionalized nanoparticle to the NH2(CH2CH2O)nCH2CH2NH2.

### Claim 15 (depends on 14)

A nanoparticle made according to the method of claim 14.

### Claim 16 (depends on 10)

The method of claim 10, wherein the targeting group is selected from the group consisting of an antibody, an antibody fragment, a peptide, an aptamer, and a small molecule.

### Claim 17 (depends on 10)

The method of claim 10, further comprising the step of purifying the unfunctionalized nanoparticle by dialysis.

### Claim 18 (depends on 10)

The method of claim 10, wherein the hydrothermal carbonization is conducted at a temperature between about 160° C. to about 240° C.

### Claim 19 (depends on 10)

The method of claim 10, wherein the nanoparticle has an average diameter of about 3 to about 3.5 nm; n is whole number selected from 3-40; the carbon matrix comprises graphitic carbon; M is Zn; or M represents two hydrogen, each of which is covalently bound to a nitrogen; and the targeting group comprising an activated carbonyl is cetuximab comprising an activated carbonyl.

### Claim 20 (depends on 19)

A nanoparticle made according to the method of claim 19.