Therapeutic Copolymer from Salicylic Acid and l-Phenylalanine as a Nanosized Drug Carrier for Orthotopic Breast Cancer with Lung Metastasis.

Abstract

Nanoparticle (NP)-mediated drug delivery systems are promising for treating various diseases. However, clinical translation has been delayed by a variety of limitations, such as weak drug loading, nonspecific drug leakage, lack of bioactivity, and short blood circulation. These issues are in part due to the unsatisfactory function of biomaterials for nanocarriers. In addition, the synthesis procedures of drug carrier materials, especially polymers, were usually complicated and led to high cost. In this report, a bioactive copolymer of hydroxy acid and amino acid, poly(salicylic acid-co-phenylalanine) (PSP), was developed for the first time via a one-step rapid and facile synthesis strategy. The PSP could self-assemble into NPs (PSP-NPs) to co-load relatively hydrophilic sphingosine kinase 1 inhibitor (PF543 in HCl salt format) and highly hydrophobic paclitaxel (PTX) to form PF543/PTX@PSP-NPs with efficient dual drug loading. Encouragingly, PF543/PTX@PSP-NPs showed long blood circulation, good stability, and high tumor accumulation, leading to significantly enhanced therapeutic effects on breast cancer. Furthermore, PF543/PTX@PSP-NPs could additionally suppress the lung metastasis of breast cancer, and more importantly, the PSP-NPs themselves as therapeutic nanocarriers also showed an anti-breast cancer effect. With these combined advantages, this new polymer and corresponding NPs will provide valuable insights into the development of new functional polymers and nanomedicines for important diseases.