Cytotoxic activity of daunomycin and adriamycin encapsulated in immunoliposomes against avian myeloblastosis virus-infected cells

Immunoliposomes were prepared using the antibody raised against the avian myeloblastosis virus envelope glycoprotein, gp80. Adriamycin was encapsulated into immunoliposomes. More drug was delivered into target cells when the drug encapsulated in immunoliposomes was incubated with the cells. The drug encapsulated in immunoliposomes was able to inhibit the RNA synthesis twice more than free drug in the virus-transformed myeloblasts. Pre-treatment of cells with ammonium chloride, reversed the effect of drug encapsulated in immunoliposomes. The drugs encapsulated in immunoliposomes had marginal effect on the RNA synthesis of non-target cells, the yolk sac cells. Colony formation by virus-transformed cells and focus formation by virus-infected yolk sac cells was inhibited significantly by the drug encapsulated in immunoliposomes.

Chemistry and biology of DNA-binding small molecules

Regulation of the transcription machinery is one of the many ways to achieve control of gene expression. This has been done either at the transcription initiation stage or at the elongation stage. Different methodologies are known to inhibit transcription initiation via targeting of double-stranded (ds) DNA by: (i) synthetic oligonucleotides, (ii) ds-DNA-specific, sequenceselective minor-groove binders (distamycin A), intercalators (daunomycin) combilexins and (iii) small molecule (peptide or intercalator)-oligonucleotide conjugates. In some cases, instead of ds-DNA, higher order G-quadruplex structures are formed at the start site of transcription. In this regard G-quadruplex DNA-specific small molecules play a significant role towards inhibition of the transcription machinery. Different types of designer DNA-binding agents act as powerful sequence-specific gene modulators, by exerting their effect from transcription regulation to gene modification. But most of these chemotherapeutic agents have serious side effects. Accordingly, there is always a challenge to design such DNA-binding molecules that should not only achieve maximum specific DNA-binding affinity, and cellular and nuclear transport activity, but also would not interfere with the functions of normal cells.