Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor-targeting small-molecule discovery to targeted nanodrug delivery

Precision medicine emphasizes patient-specific formulation for treatment of diseases, especially cancer. However, in targeted cancer treatment, because the expression level of tumor receptors in each patient varies even for the same type of cancer, the ligand/receptor-mediated approach does not seem promising for precision medicine. In this work, we demonstrated our strategy of using a phage display technique for breast cancer precision medicine. Using in vivo biopanning, we first selected an MCF-7 breast tumor-targeting peptide, then tested the effectiveness of the as-selected peptide in tumor homing and finally conjugated the peptide to a model photothermal drug, namely, gold nanorods, to achieve enhanced cancer killing efficacy. The peptides identified by the phage display technique can guide the drug to the tumors without the need to know the exact receptors on the tumor. This approach requires significantly less effort to explore patient-specific targeting molecules for precision medicine. Peptide-assisted delivery of cancer-killing gold nanorods can be customized to a patient's specific tumor receptors using bacteriophages. Drug formulations that incorporate tumor-recognizing molecules make chemotherapies safer and more effective. Chuanbin Mao from the University of Oklahoma, USA, and Zhejiang University, China, and colleagues have shown that phages can automatically select optimal peptides for this approach. The team injected libraries with billions of phages into mice carrying breast cancer cells, and extracted those which bound most strongly to tumors after 1 hour. These biomolecules were then used as inputs for another round of testing, and, after five sequences of 'biopanning', phages with the highest tumor affinity emerged. Adding phage-selected peptides to gold nanorods improved drug uptake by 63% compared to a control group, and enabled subsequent laser treatment to destroy tumors at power densities safe enough for normal tissue. We have developed a phage display-based solution for breast cancer precision medicine. The patient-specific tumor-targeting peptide was first selected through in vivo biopanning. The as-selected peptide was then coupled with an anti-cancer nanomaterial drug. Enhanced nanodrug accumulation was achieved, which resulted in improved tumor killing efficacy. This study demonstrates a systematic strategy for discovering and testing patient-specific tumor targeting small molecules for cancer precision medicine.