The effect of the structure of branched polypeptide carrier on intracellular delivery of daunomycin.

The conjugate of acid labile cis-aconityl-daunomycin (cAD) with branched chain polypeptide, poly[Lys(Glui-DL-Alam)] (EAK) was very effective against L1210 leukemia in mice. However, Dau attached to a polycationic polypeptide, poly[Lys(Seri-DL-Alam)] (SAK) exhibited no in vivo antitumor effect. In order to understand this difference we have performed comparative in vitro studies to dissect properties related to interaction with the whole body (e.

Interfacial interactions of hydrophobic peptides with lipid bilayers.

Four hydrophobic laminin-related peptides and their corresponding parent peptides were synthesized to use them to target liposomes to tumoral cells. The peptide sequence was YIGSR((NH(2))), and hydrophobic residues linked to the alpha-amino terminal end were decanoyl, myristoyl, stearoyl, and cholesteryl-succinoyl. Before use in biological systems, a physicochemical study was carried out in order to determine their interaction with DPPC bilayers that could compromise both the toxicity and the stability of liposomal preparations.

Targeted adriamycin delivery to MXT-B2 metastatic mammary carcinoma cells by transferrin liposomes: effect of adriamycin ADR-to-lipid ratio.

In the protein-targeted therapy for cancer, transferrin (Tf) is used to reach a selective and specific target in cancer cells. Tf is used conjugated to chemotherapeutic drugs, insulin, toxins, antibodies, polymers, nanoparticles, lipoplexes and liposomes. Using this latter approach, hydrophobically derivatized Tf was incorporated to liposomal bilayers.

In vitro effects of SIKVAV retro and retro-enantio analogues on tumor metastatic events.

The SIKVAV peptide, located on the long arm of the laminin alpha1 chain, promotes cell adhesion, invasion and migration of tumor and endothelial cells, resulting in tumor growth, angiogenesis and metastasis. In this paper, we report the synthesis of the SIKVAV peptide and its retro (reverse l-amino acid order) and retro-enantio (reverse d-amino acid order) analogues and their effect on three critical steps in the metastatic process: cell-extracellular matrix protein (ECM) adhesion, cell migration and homotypic cell adhesion, using B16F10 melanoma cells. Results show that all peptides compete with laminin-1 cell attachment, but only SIKVAV induces peptide-cell adhesion.

Biodistribution study of doxorubicin encapsulated in liposomes: influence of peptide coating and lipid composition.

In this paper we describe the biodistribution of doxorubicin (DXR) encapsulated in three different types of liposomes. Common composition was hydrogenated phosphatidylcholine (HPC)/phosphatidylglycerol (PG) cholesterol (Chol)/X, X being either 10% N-glutaryl phosphatidylethanolamine (NGPE), 10% NGPE + 6% distearoyl-phosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG), or 10% NGPE + 6% DSPE-PEG-COOH. These series of vesicles were coated with an active or an inactive sequence of laminin (laminin receptors, integrins, are overexpressed in tumor cells).

Optimization study of doxorubicin liposomal preparations coated with laminin fragments.

Immunoliposomes, coated with two peptide sequences and loaded with doxorubicin, were prepared. The influence of different parameters in the sequential steps of liposomal preparations was studied as, for instance, lipid composition, size reduction methods, elimination of non-entrapped drug, and peptide coating sequence. Results were evaluated, such as entrapment efficiency, phospholipid/drug and phospholipid/peptide relationship, and size of final preparations.

Hydrophobic Laminin-Related Peptides: Synthesis and Surface Properties.

The synthesis of hydrophobic peptide derivatives related to the laminin sequence [YIGSR(NH(2))] is described. Hydrophobicity is achieved by the attachment of decanoic, myristic, or stearic acids to the amino terminal end of the peptide. Moreover, a cholesterol residue was also introduced as succinimidoyl-cholesteryl moiety at the same position.