Abstract
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.
Highlights
In the most recent decade, targeted drug delivery has been studied intensively for cancer treatment.[1,2,3,4] This method involves the use of tumor-recognizing molecules in the drug formulation to enhance drug accumulation in cancerous tissue
We intend to demonstrate a new strategy for breast cancer precision medicine using MCF-7 breast cancer-bearing mice as the model in which a tumor-homing peptide customized to a specific patient is first identified without the need to know what receptors this peptide recognizes and is subsequently linked with cancer nanomedicine to selectively inhibit the tumor (Figure 1)
In brief, in vivo phage display was performed in several rounds of affinity testing against MCF-7 tumors in vivo
Summary
In the most recent decade, targeted drug delivery has been studied intensively for cancer treatment.[1,2,3,4] This method involves the use of tumor-recognizing molecules in the drug formulation to enhance drug accumulation in cancerous tissue. As each type of cancer differs in many ways in different patients, especially on the molecular level, the tumor receptor-based targeted delivery strategy might not work as well for precision medicine, because the expression level of the receptors might vary dramatically among patients This is one of the reasons why current cancer therapeutics show low survival rates. We show that without considering the unique receptors of breast tumors, we are able to discover novel peptides capable of preferentially recognizing the tumors via the phage display technique This approach is possible because identification of targeting peptides by phage display in principle does not require prior knowledge of the target and peptides with affinities to unknown types of tumors can be selected in a fast and cost-effective manner, allowing us to identify patient-specific tumor-homing peptides. We demonstrate such a strategy by performing the entire procedure from the discovery of tumor-homing peptides to the eventual validation of Received 25 March 2017; revised 27 August 2017; accepted 21 September 2017
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