Improved tumor targeting and penetrating by dual-functional poly(amidoamine) dendrimer for the therapy of triple-negative breast cancer
Epidermal growth factor receptor (EGFR) has been proven to be a validated therapeutic target for triple-negative breast cancer, a refractory carcinoma with high malignancy and poor prognosis. In this work, an EGFR targeting peptide, EGFR-binding peptide 1 (EBP-1), was identified by screening a “one-bead one-compound” (OBOC) combinatorial library. EBP-1 was demonstrated to have high affinity and specificity towards EGFR at both molecular and cellular levels. A dual-functional drug delivery system based on poly(amidoamine) (PAMAM) dendrimer conjugated with EBP-1 and the cell penetrating peptide which derived from trans-activating transcriptional activator (TAT) was established and used for encapsulating doxorubicin (DOX). This dual-functional drug carrier significantly improved the anti-proliferation effect of chemotherapeutic drugs against human breast cancer MDA-MB-231 cells in vitro compared with free DOX and mono-functional carriers. Modification of the dendrimer with EBP-1 and TAT peptides significantly improved drug accumulation in tumor site in vivo, resulting in strikingly superior efficacy in tumor growth inhibition and prolonged survival. These results provide evidences that peptide EBP-1 would be a promising ligand towards EGFR for targeted drug delivery, and the dual-functional carrier can be used as a potential tumor targeting drug carrier for tumor therapy.