Thermosensitive Micelles Encapsulating Phenylalanine Ammonia Lyase Act as a Sustained and Efficacious Therapy Against Colorectal Cancer.

Colorectal cancer has become the third most commonly diagnosed cancer worldwide, which has posed challenges to current conventional therapies. Hence, we propose an alternative approach to the existing therapeutics for colorectal cancer treatment. In this work, we prepared thermosensitive micelles based on poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers (PAL-micelles) that were used to encapsulate phenylalanine ammonia lyase (PAL) as an in situ sustained drug delivery system. In vitro experiments suggested that PAL could inhibit the proliferation and induce apoptosis of tumor cells because the depletion of local phenylalanine blocked the synthesis of corresponding proteins. In addition, the release behavior in vitro and in vivo showed that PAL could be released from PAL-micelles in a controlled manner. Moreover, a significant inhibition of tumor growth was observed in the PAL-micelles-treated xenograft mouse model compared to the control groups in vivo, but the systemic toxicity was not noteworthy. The antitumor efficacy was further confirmed by histological analysis of the tumor tissues with hematoxylin and eosin (H&E) and Ki-67 staining. The above results demonstrated that the PAL-micelles system could be considered an alternative strategy for colorectal cancer treatment.