M13 bacteriophage as a chemoaddressable nanoparticle for biological and medical applications
Reactive and modified M13 bacteriophages, and methods of making and using the same, are generally provided. The reactive M13 bacteriophage can include a alkyne functional group covalently attached to the M13 bacteriophage. The modified M13 bacteriophage can include a substituent covalently attached to the M13 bacteriophage via a 1,2,3-triazole linkage. Dual-modified M13 bacteriophages are also generally provided, and can include a cancer-targeting substituent covalently attached to the M13 bacteriophage and a fluorescent group covalently attached to the M13 bacteriophage. The modified M13 bacteriophages can not only be employed as a fluorescent probe for cancer imaging, but also can be used as biomaterials for cell alignment and scaffolding.
1. A dual-modified M13 bacteriophage comprising
a M13 bacteriophage;
a cancer-targeting substituent covalently attached to the M13 bacteriophage via a 1,2,3-triazole linkage and a benzene diazonium linkage; and
a fluorescent group covalently attached to the M13 bacteriophage.
2. The dual-modified M13 bacteriophage of claim 1 , wherein the cancer-targeting substituent comprises folic acid.
3. The dual-modified M13 bacteriophage of claim 1 , wherein the cancer-targeting substituent is covalently attached to the M13 bacteriophage via an amino group of a N-terminal amino acid or an amino functional group of a lysine amino acid.
4. The dual-modified M13 bacteriophage of claim 1 , wherein the fluorescent group is covalently attached to the M13 bacteriophage via a carboxyl group on the M13 bacteriophage.
5. The dual-modified M13 bacteriophage of claim 1 , wherein the fluorescent group comprises fluoresceinamine or N,N,N′,N′-tetramethylrhodamine.
6. A method of fluorescently marking tumor cells, the method comprising
exposing the dual-modified M13 bacteriophage of claim 1 to the tumor cells.
7. The method of claim 6 , wherein the fluorescent group is covalently attached to the modified M13 bacteriophage via a terminal amine of an amino acid or a functional amino group of a lysine amino acid.
8. The method of claim 6 , wherein the cancer-targeting substituent is covalently attached to the modified M13 bacteriophage via a 1,2,3-triazole linkage.
9. The dual-modified M13 bacteriophage of claim 1 , wherein the M13 bacteriophage comprises the structure:
wherein R represents the cancer-targeting substituent.
10. The dual-modified M13 bacteriophage of claim 1 , wherein the fluorescent group is covalently attached to the M13 bacteriophage via an amine group and/or a carboxyl group of the M13 bacteriophage and wherein the cancer-targeting substituent is covalently attached to the M13 bacteriophage via a tyrosine amino acid of the M13 bacteriophage.
11. The dual-modified M13 bacteriophage of claim 10 , wherein the fluorescent group is covalently attached to the M13 bacteriophage via an N-terminal amino group of the M13 bacteriophage.
12. The dual modified M13 bacteriophage of claim 10 , wherein the fluorescent group is covalently attached to the M13 bacteriophage via an alanine amino acid or via a lysine amino acid of the M13 bacteriophage.