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

• Published in: ACS applied materials & interfaces Vol. 13; no. 42; pp. 49658 - 49670
• Main Authors: Meng, Yabin, Wu, Jun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.10.2021
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biological and Medical Applications of Materials and Interfaces; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Liberation; Drug Screening Assays, Antitumor; Female; Humans; Materials Testing; Mice; Mice, Inbred BALB C; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Paclitaxel - chemistry; Paclitaxel - pharmacology; Phenylalanine - chemical synthesis; Phenylalanine - chemistry; Polymers - chemical synthesis; Polymers - chemistry; Rats; Rats, Sprague-Dawley; paclitaxel; nanoparticle; poly(phenylalanine); colorectal cancer; drug carrier
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c13013

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.