One-Step and Facile Synthesis of Poly(phenylalanine) as a Robust Drug Carrier for Enhanced Cancer Therapy

In recent decades, many poly(amino acid)s have been successfully prepared for various biomedical applications. To date, the synthesis and purification procedures used to generate these poly(amino acid)s have generally been complicated and costly. Here, a one-step synthesis strategy was developed and optimized via direct polymerization using thionyl chloride to easily and economically obtain poly(amino acid)s. Phenylalanine (Phe) was selected as a model amino acid to construct a family of biodegradable and biocompatible poly(phenylalanine) (PPhe) molecules with a tunable molecular weight. The prepared PPhe can self-assemble into nanoparticles (PP-NPs) through nanoprecipitation with a particle size of approximately 100 nm. PP-NPs exhibit a high drug-loading capacity (>12 wt %) of paclitaxel (PTX, a commercial antitumor drug) and good therapeutic effects in CT26 cells. The in vivo evaluation of PTX@PP-NPs indicates that it has a prolonged blood circulation time and high tumor aggregation after intravenous injection, resulting in significant antitumor effects in CT26 tumor-bearing mice with minimal toxicity to normal organs. Overall, this study provides a facile and simple strategy for synthesizing poly(amino acids) and a PPhe-based nanoparticle platform for effectively delivering various small-molecule drugs.