Novel modular transporters delivering anticancer drugs and foreign DNA to the nuclei of target cancer cells.
A major challenge in the development of specific and effective cancer treatments is the paradoxical situation that exploiting a molecular target that is accessible (surface membrane or extracellular matrix) is critical for achieving tumor selectivity whereas delivery of the therapeutic inside the cell, to the cell nucleus is generally required for maximizing the therapeutic effect. Photosensitizers, alpha-particle emitting radionuclides and foreign genetic material could be considered as such therapeutics if they possessed cellular and subcellular specificity. The author describes a novel approach of using modular recombinant transporters to target the therapeutics to the nucleus of cancer cells, where their action is most pronounced or can only be expressed. Photo-sensitizer-transporter conjugates displayed up to 3000 times greater efficacy than free photosensitizers and acquired cell specificity in contrast to free photosensitizers. Alpha-emitting radionuclides, conjugated with the modular transporters, acquired similar properties. DNA complexed with analogous transporters efficiently transfected target cells. The different modules of the transporters are interchangeable, meaning that they can be tailored for particular applications.
Sobolev
A S
AS
Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Moscow, Russia. sobolev@igb.ac.ru
D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014780:Viruses / Q000235:genetics
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011994:Recombinant Proteins; D004247:DNA