Landscape phage fusion protein-modified pharmaceutical nanocarriers for targeted and cytoplasmic delivery of chemotherapeutics to breast cancer cells in vitro and in vivo

• Online Access: http://hdl.handle.net/2047/d20002706

Objective : Conventional chemotherapy is often accompanied by severe side-effects in cancer treatment owing to its inability to kill tumor cells specifically. The use of targeted pharmaceutical nanocarriers has improved the pharmacokinetic and pharmacodynamic properties of chemotherapy. Ongoing challenges for targeted delivery include the search for alternative ligands (e.g. "substitute antibodies") and development of methods for their conjugation with nanomedicines. The phage display technique is emerging as a powerful tool to identify tumor recognition molecules. The objective of the project is to integrate phage display technology with nanocarrier-based drug delivery systems (liposomes and micelles) for advanced targeted drug delivery. The traditional phage display approach for targeted delivery assumes the necessity of a chemical synthesis of identified tumor-selective peptides and their conjugation with pharmaceuticals or pharmaceutical nanocarriers. Here, we have proposed a new approach using a phage fusion protein (a tumor specific peptide fused to the phage pVIII coat protein) to avoid drawbacks associated with chemical modifications, and improve the therapeutic index of anti-tumor agents by the integration of nanomedicines and phage display techniques.