Theranostics 2016; 6(8):1261-1273. doi:10.7150/thno.14302 This issue Cite
Research Paper
1. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China;
2. CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China;
3. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
4. Pharmacy College, Liaoning Medical University, Jinzhou, Liaoning 121001, China.
*These authors contributed equally to this work.
Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery.
Keywords: HER2 targeting peptide, tumor imaging, drug delivery, breast cancer, MD simulation.