Functionalized porous silicon nanoparticles and use thereof in photodynamic therapy

Patent metadata

Field	Value
Publication number	US-9694074-B2
Application number	US-201314388860-A
Country	US
Kind code	B2
Filing date	Mar 26, 2013
Priority date	Mar 27, 2012
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

Disclosed are nanovectors of formula (I) that can be used simultaneously for the targeting, imaging and treatment, by photodynamic therapy, of cancer cells, and to biodegradable silicon nanoparticles containing a variety of photosensitizing molecules, in particular porphyrins, capable of targeting diseased cells and inducing cell death by excitation in the near-infrared region (>600 nm) in monophotonic and biphotonic modes. In formula (I), (AA) is a porous silicon nanoparticle.

First claim

The invention claimed is:

1. Nanoparticles corresponding to formula (I):

in which:

represents a porous silicon nanoparticle,
x represents 0 or 1,
M represents a transition metal atom,
X represents a halide or an anion of a pharmaceutically acceptable carboxylic acid,
R represents a urea (—NH—CO—NH—) or a thiourea (—NH—CS—NH—),
W represents a C1-C12 alkanediyl group,
R′ represents:

Z + represents a pharmaceutically acceptable organic or mineral cation,
Y − represents —COO − or —SO 3 − ,
A − represents a halide or an anion of a pharmaceutically acceptable carboxylic acid, and
R1 represents a C1 to C10 alkyl group.

2. The nanoparticles according to claim 1 corresponding to formula (Ia):

wherein Cbg represents a specific targeting molecule for neoplastic tissues.

3. The nanoparticles according to claim 2 , the size of which is from 20 to 200 nm.

4. The nanoparticles according to claim 2 , in which x represents 0.

5. The nanoparticles according to claim 2 , in which:
X represents a group selected from the group consisting of: Cl − , Br − , I − , acetate, propionate, butyrate, ascorbate, benzoate, cinnamate, citrate, fumarate, glycolate, malonate, tartrate, malate, maleate, mandelate, and tosylate,
W represents a —(CH 2 ) 3 — group,
R′ is:

and
Cbg is selected from the group consisting of folic acid, peptides, carbohydrates and antibodies.

6. A method for producing nanoparticles according to claim 2 , said method comprising the steps of:
(i) providing porous silicon nanoparticles,
(ii) functionalizing the porous silicon nanoparticles with groups comprising at least one C1-C12 NH 2 function or at least one C1-C12 isocyanate or C1-C12 isothiocyanate,
(iii) providing and grafting a porphyrin-type photosensitizing molecule corresponding to formula (II),

in which:
x represents 0 or 1,
M represents a transition metal atom,
X represents a halide or an anion of a pharmaceutically acceptable carboxylic acid,

Q represents a group selected from the group consisting of —NH 2 , —N═C═O, and —N═C═S,
R′ represents:

Z + represents a pharmaceutically acceptable organic or mineral cation,
Y − represents —COO − or —SO 3 − ,
A − represents a halide or an anion of a pharmaceutically acceptable carboxylic acid, and
R1 represents a C1 to C10 alkyl group, and optionally
(iv) grafting with at least one targeting molecule.

7. The nanoparticles according to claim 1 , the size of which is from 20 to 200 nm.

8. The nanoparticles according to claim 7 , in which x represents 0.

9. The nanoparticles according to claim 7 , in which:
X represents a group selected from the group consisting of: Cl − , Br − , I − , acetate, propionate, butyrate, ascorbate, benzoate, cinnamate, citrate, fumarate, glycolate, malonate, tartrate, malate, maleate, mandelate, and tosylate,
W represents a —(CH 2 ) 3 — group,
R′ is:

10. The nanoparticles according to claim 1 , in which x represents 0.

11. The nanoparticles according to claim 10 , in which:
X represents a group selected from the group consisting of: Cl − , Br − , I − , acetate, propionate, butyrate, ascorbate, benzoate, cinnamate, citrate, fumarate, glycolate, malonate, tartrate, malate, maleate, mandelate, and tosylate,
W represents a —(CH 2 ) 3 — group,
R′ is:

12. The nanoparticles according to claim 1 , in which:
X represents a group selected from the group consisting of: Cl − , Br − , I − , acetate, propionate, butyrate, ascorbate, benzoate, cinnamate, citrate, fumarate, glycolate, malonate, tartrate, malate, maleate, mandelate, and tosylate,
W represents a —(CH 2 ) 3 — group, and
R′ is:

13. The nanoparticles according to claim 12 , wherein the nanoparticles have a structure according to one of:

14. A method for producing nanoparticles according to claim 1 , said method comprising the steps of:
(i) providing porous silicon nanoparticles,
(ii) functionalizing the porous silicon nanoparticles with groups comprising at least one C1-C12 NH 2 function or at least one C1-C12 isocyanate or C1-C12 isothiocyanate, and
(iii) providing and grafting a porphyrin-type photosensitizing molecule corresponding to formula (II),

in which:
x represents 0 or 1,
M represents a transition metal atom,
X represents a halide or an anion of a pharmaceutically acceptable carboxylic acid,

Q represents a group selected from the group consisting of —NH 2 , —N═C═O, and —N═C═S,
R′ represents:

Z + represents a pharmaceutically acceptable organic or mineral cation,
Y − represents —COO − or —SO 3 − ,
A − represents a halide or an anion of a pharmaceutically acceptable carboxylic acid, and
R1 represents a C1 to C10 alkyl group.

15. The method according to claim 14 , which comprises the steps of:
(i) a—electrochemical etching of monocrystalline silicon plates in a hydrofluoric (HF) ethanol solution,
b—removal of the porous film and treatment by ultrasound,

(ii) a—controlled oxidation followed by silanization so as to produce Si—OH groups and SiO 2 species on the surface of the porous silicon nanoparticles, and treatment by an aminoalkylsilanyl group, and/or
b—hydrosilylation with a C1-C12 allylamine, C1-C12 allyl isocyanate or C1-C12 allyl isothiocyanate, and

(iii) grafting the porous nanoparticles of step (ii) with a porphyrin-type photosensitizing molecule corresponding to formula (II).

16. A medicinal composition comprising nanoparticles according to claim 1 in a pharmaceutically acceptable support.

17. A cosmetic composition comprising nanoparticles according to claim 1 in a cosmetically acceptable support.

18. A kit for the detection, treatment, monitoring, prevention, and delay of the appearance and/or recurrence of a pathology selected from the group consisting of cancers, tumors, and cell proliferation diseases, comprising:
nanoparticles according to claim 1 , and
means that allow an irradiation in the infrared.

Assignees

• Centre Nat De La Rech Scient (Cnrs)
• Univ Montpellier 2 Sciences Et Techniques
• Univ California
• Enscm

Inventors

• Cunin Frederique
• Durand Jean-Olivier
• Sailor Michael J
• Garcia Marcel
• Secret Emilie
• Gary-Bobo Magali
• Maynadier Marie
• Morere Alain

Classifications

• A61K31/315

  Zinc compounds · CPC title

• A61K31/409

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title

• A61K31/28

  Compounds containing heavy metals · CPC title

• A61K41/008

  Two-Photon or Multi-Photon PDT, e.g. with upconverting dyes or photosensitisers · CPC title

• Y10T428/2982

  Particulate matter [e.g., sphere, flake, etc.] · CPC title