LTVSPWY peptide–modified PEGylated chitosan magnetic nanoparticles

Large biomolecules such as antibodies (Ab) have been extensively investigated and used for the delivery of drugs (as Ab-drug conjugates) to treat cancers, but a major limitation of using such drug delivery vehicles is that the Ab-drug conjugates are not able to penetrate deeply into solid tumors due to their large size; in addition, the conjugates may evoke an immune response, and they tend to accumulate in the liver and the reticuloendothelial system of an animal (1). Small molecules such as peptides have been shown to be efficient drug carriers, particularly if they are able to pass through the cell membrane and penetrate into the cell (such peptides are known as cell-penetrating peptides; CPP). The exact mechanism by which the CPP-drug conjugate (CPP-D) is taken up by the cells is not well understood; it is believed that the these peptides first interact with the surface and lipid components of the cell membrane, and then the CPP-D is internalized by the cell through the process of endocytosis (1). For a detailed discussion on CPPs, see Milletti (2). The heptapeptide LTVSPWY, which has a high binding specificity for human mammary adenocarcinoma SKBR3 cells, was identified after the screening of several commercially available random peptide phage display libraries (3). It was shown that this peptide could be used to deliver an antisense oligonucleotide directed against the human epidermal growth factor receptor 2 (HER2, ErbB2) for internalization by the SKBR3 cells, which overexpress HER2 (3). Investigators have also reported that the LTVSPWY peptide can be used for the delivery of anticancer drugs (4, 5) and cytotoxic peptides (6) to cells under (4-6) or (5) conditions. On the basis of these studies, the biodistribution and imaging characteristics of LTVSPWY peptide–modified PEGylated chitosan magnetic nanoparticles (MNPs; LTVSPWY-PEG-CS MNPs) were studied in mice bearing SKOV-3 cell tumors, which overexpress HER2 (7).