B16(F10) /murine melanoma/, BAEC /bovine aortal/ and MCF-7 /human breast cancer/ cultured cells, which differ in integrin receptor levels, were treated with RGD-4C-GG-_D(KLAKLAK)₂ antivascular oligopeptide or control peptides. LC₅₀ by MTT was determined. The RGD peptide proved the most toxic for melanotic cells (LC₅₀= 5μM). TUNEL demonstrated that 3-h incubation with the antivascular peptide induced apoptosis only in melanotic and breast cancer cells. Antitumor therapy with RGD-4C-GG-_D(KLAKLAK)₂ on 11^th day brought about slower tumor growth compared to controls. Antivascular peptide monotherapy did not, however, extend mice survival.

Liposomes made of distearoylphosphatidylocholine (DSPC), cholesterol and distearoylphosphatidylethanoloamine conjugated with N-carbamoylmethoxypolyethylene-glycol /non-targeted, long-lived liposomes (NTL)/ or with additional distearoylphosphatidylethanolamine-N-carbamoyl-methoxypolyethyleneglycol-folic acid (DSPE-PEG-folate) /folate-targeted, long-lived liposomes, (FTL )/ were prepared to allow carrier-mediated transfer of a chemotherapeutic (doxorubicin). Liposomes were extruded and dialyzed. Doxorubicin was internalized (in excess of 95%) using transmembrane pH gradient. Phospholipid and folic acid concentration were assessed and liposome size measured using dynamic light scattering. Doxorubicin transfer in vitro was examined by flow cytometry (λ_ex=488nm, λ_em=550nm); doxorubicin fluorescence histograms showed that essentially all B16(F10) cells internalized both types of drug-carrying liposomes. Intracellular localization of doxorubicin was checked by confocal microscopy; this demonstrated that significant amounts of doxorubicin were found in endosomes, cytoplasm and nucleus. Therapy of B16(F10) tumor-bearing C57Bl6 mice with varying amounts of both types of doxorubicin-carrying liposomes showed that tumor growth was slower for both NTL and FTL, as compared with controls. Life span of animals was significantly extended. Furthermore, transfer of liposomes equivalent to 4 doses of 50μg doxorubicin each demonstrated that ligand-bearing liposomes were slightly more efficient in mediating the drug transfer, as judged from tumor growth kinetics and survival data.

On-going experiments involve combinatory therapy with antivascular RGD oligopeptide and doxorubicin-carrying liposomes.

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