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1. (WO2007008376) USE OF ONE OR MORE METAL CARRIERS TO SELECTIVELY KILL MAMMALIAN CELLS
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Claims
1. A two component composition to induce cell death comprising:
a first carrier comprising a peptide or protein carrying more than one metal ion that is cell impermeable or slowly permeable and that associates with the cell; and a second carrier comprising a cell permeable dithiocarbonyl compound that transports the protein/peptide-bound metal ion into the cell.
2. The composition of claim 1, wherein the first carrier is a sulfur-rich peptide or protein that binds at least two metal ions.
3. The composition of claim 1, wherein the first carrier is a sulfur-rich peptide or protein that binds three to seven metal ions.
4. The composition of claim 2 wherein the protein is metallothionein.
5. The composition of claim 2 wherein the peptide is substantially similar to metallothionein isolated from Neurospora crassa.
6. The composition of claim 2, wherein the peptide has an amino acid sequence of: KDCGCSGASSCNCGSGCSCSNCGSG (SEQ ID NO: 1) .
7. The composition of claim 1 wherein the first and second carriers bind cadmium (II), zinc (II), copper (I), silver (I), cobalt (II), mercury (II), iron (II), gold (I), bismuth (III), nickel (II), lead (II), or platinum (II).
8. The composition of claim 1 wherein the first and second carriers bind cadmium (II).
9. The composition of claim 1 wherein the first and second carriers bind zinc (II).
10. The composition of claim 1 wherein the first carrier further comprises a targeting moiety to substantially direct the first carrier to targeted cells or tissues.

11. The composition of claim 1 wherein the first carrier is bound to
nanoparticles or nanocells.
12. The composition of claim 11 wherein the nanoparticles or nanocells direct the first carrier to targeted cells or tissues.
13. The composition of claim 11 wherein the nanoparticles or nanocells further comprise polyethyleneglycol.
14. The composition of claim 10 wherein the first carrier is a metallothionein or a peptide derived from or substantially similar to a partial or whole amino acid sequence of a metallothionein.

15. The composition of claim 11 wherein the first carrier is a metallothionein or a peptide derived from or substantially similar to a partial or whole amino acid sequence of a metallothionein.
16. The composition of claim 12 wherein the first carrier is a metallothionein or a peptide derived from or substantially similar to a partial or whole amino acid sequence of a metallothionein.
17. The composition of claim 13 wherein the first carrier is a metallothionein or a peptide derived from or substantially similar to a partial or whole amino acid sequence of a metallothionein.
18. The composition of claim 1, wherein the second carrier is a compound represented by the formula:
(ROn1(R2)Z-C-(S)-S-Y
wherein:
m is 0 or 1;
Ri and R2 may be independently hydrogen or C1-C24 straight,
branched, or cyclic alkyl, alkenyl, aryl, alkaryl, aralkyl, or
alkoxy fragments, said fragments optionally substituted with
ester, ether, halogen, ether, sulfate, hydroxyl, or phosphate
groups or wherein Ri and R2 may be optionally connected
via a bridge comprising -(CEk)n-, wherein n is 3-8, and
wherein said bridge may be optionally substituted with Cl- ClO straight, branched, or cyclic alkyl, aryl, aryalkyl, or
alkaryl groups, each of said groups optionally substituted
with hydroxyl, halo, phosphate, sulfate, or sulfonate groups; Z is oxygen or nitrogen with the proviso that if Z is oxygen
then m is 0; and
Y is hydrogen, Cl -C 12 amine, Cl -C 12 carboxyl, a
pharmaceutically acceptable cation, a physiologically
cleavable leaving group, a targeting moiety, or a
chemotherapeutic drug.
19. The composition of claim 1, wherein the second carrier is dithiocarbonyl compound or a derivative thereof.
20. The composition of claim 1 wherein the second carrier is
aminopropylpiperidine-1-carbodithioate HCl or a derivative thereof.

21. The composition of claim 1 , wherein the second carrier is
pyrrolidinecarbodithioic acid, 3-aminopropylpiperidine-l-carbodithioate HCl or a derivative thereof.
22. The composition of claim 1 wherein the second carrier further comprises a targeting moiety to substantially direct the second carrier to targeted cells or tissues.
23. A metal containing compound comprising
a metal ion; and
an aminodithiocarbonyl compound modified by a targeting moiety to substantially direct the compound to targeted cells or tissues.
24. A metal containing compound according to claim 23 wherein the aminodithiocarbonyl compound is 3-aminopropylpiperidine-l-carbodithioate HCl or a derivative thereof.
25. A method of inducing cell death comprising the steps of:
exposing a cell or tissue site with a metal-peptide complex for a predetermined period of time to provide a source of metal ions at the cell or tissue site; and
exposing the source of metal ions with a dithiocarbonyl compound to carry the metal into the cell to induce cell death.
26. The method of claim 25 wherein the contacting steps comprise intravenous, intraarterial, subcutaneous, intraperietal, intradermal, intratissue, intramuscular, intracerebral, aerosol, or topical delivery routes.
27. A method of claim 25 wherein the dithiocarbonyl compound is metal-free, 3-aminopropylpiperidine-l-carbodithioate HCl or a derivative thereof modified with a suitable targeting moiety.
28. A method of inducing targeted cell death comprising the step of:
contacting a targeted cell or tissue site with a dithiocarbonyl compound comprising a source of metal ions and a targeting moiety, wherein the
dithiocarbonyl compound carries the metal ion into the targeted cell to induce cell death.
29. A method of claim 28 wherein the contacting step is oral, intravenous, intraarterial, subcutaneous, intraperietal, intradermal, intratissue, intramuscular, intracerebral, aerosol, or topical delivery.