Author/Authors :
Kolesanova, E.F Institute of Biomedical Chemistry, Moscow, Russia , Melnikova, M.V Institute of Biomedical Chemistry, Moscow, Russia , Bolshakova, T.N N.F. Gamaleya Federal Research Center of Epidemiology and Microbiology, Moscow, Russia , Rybalkina, E.Yu Institute of Carcinogenesis - Federal National Medical Research Center of Oncology, Moscow, Russia , Sivov, I.G Biotechnologiya, Ltd., Moscow, Russia
Abstract :
Bacteriophage MS2 was employed for targeted delivery of an apoptosis-inducing agent, Tl+, into a tu-mor tissue. The targeted delivery was ensured by iRGD peptide, a ligand of integrins presumably located on the surface of endotheliocytes of the tumor tissue neovasculature and certain tumor cells. The synthesized peptide was conjugated to MS2 capsid proteins. Tl+ ions from TlNO3 penetrated the phage particles and tightly bound to phage RNA. Peptide-modified MS2 preparations filled with Tl+ caused cell death in two types of cultivated human breast cancer cells and effected necrosis of these tumor xenografts in mice. Neither peptide-conjugated bacteriophage MS2 without Tl+ nor the phage filled with Tl+ but without the peptide or the same phage with the non-conjugated peptide in solution produced such effects. The preparation exhibited no acute toxicity at a therapeutic dose.
Keywords :
breast cancer , targeted therapy , thallium (I) ions , iRGD peptide , bacteriophage MS2
