Abstract

Graphical A simple strategy was used to fabricate a dual pH-responsive nanoplatform of calcium phosphate modified with polyacrylic acid and loaded with Paeonol (Pae@CA-P/PAA NPs) for breast tumor treatment. In spite of several treatments involving chemotherapy, immunotherapy, and molecularly targeted agents, patients with metastatic breast cancers (MBCs) usually have a poor prognosis due to the toxic side effects, poor selectivity, and drug resistance of these treatments. Thus, new effective treatments with reduced side effects are needed. Paeonol (Pae), a bioactive phenol, has anti-tumor activity, but hydrophobicity, poor bioavailability, and instability limit its anti-tumor effect. To overcome these problems, we constructed a nanoplatform of calcium phosphate (CA-P) modified with polyacrylic acid (PAA) and loaded with Pae (Pae@CA-P/PAA NPs). Pae@CA-P/PAA NPs possess high drug-loading levels and dual pH-responsive properties. Because of the weak acidity of the tumor microenvironment (TME), the platform can passively target tumor sites. Compared with free Pae, Pae@CA-P/PAA NPs effectively inhibited tumor cell growth and metastasis in vitro and in vivo. In conclusion, the nanoplatform is a promising strategy for the therapy of MBCs.