| Cancer targeting using peptides has demonstrated great potential for targeted anticancer therapies. This project was aimed to examine the biorecognizability of HPMA copolymer containing lymphoma targeting peptides. In the first phase, peptides which specifically recognize CD21 receptor, a cell surface marker of lymphoma, were identified with two different combinatorial peptide libraries: a phage display library and an one-bead one-compound (OBOC) peptide library. Five distinctive pentadecapeptides were identified as ligands for the CD21 receptor using phage display, and four heptapeptides were identified using the OBOC method. Their dissociation constants were determined to be within micromolar range with fluorescence quenching. Then, the biorecognizability of selected peptides were investigated after conjugation with HPMA copolymers. The HPMA copolymer-peptide conjugates were demonstrated to retain the biorecognizability towards the CD21 receptor in surface binding studies. In addition, it was found that multivalent interactions were critical for biorecognition between HPMA copolymer-peptide conjugates and surface-bound receptors. The importance of a spacer between the peptide and the HPMA copolymer backbone was also investigated. Finally, the self-association properties of HPMA copolymers containing an amphipathic heptapeptide (YILIHRN) were evaluated using fluorescence resonance energy transfer (FRET) studies. The influence of self-association on the biological properties of HPMA copolymer-peptide conjugates was demonstrated with studies on enzymatic release of model drugs. |
