Multi-functional engineered polypeptide-based drug delivery systems for improved cancer therapy

With the rapid development of chemical engineering and biotechnology, polypeptide, as a promising candidate in the biomedical field, has been thoroughly investigated and extensively used as the drug delivery vehicle for diseases treatment, especially cancer, owing to the high biocompatibility, good biodegradability, versatile constructions, and diverse functions. Engineered polypeptide-based drug delivery system (so-called EPP-DDS) can deliver the cargos to the target site via a specific recognition effect, followed by overcoming the barriers like blood brain barrier (BBB) and releasing them by responding to the microenvironment cues, to improve the therapeutic efficacy and reduce the side-effect. Herein, it's of great importance to conclude and summarize the updates on EPP-DDS developed by chemical engineering methods. In this review, we first summarized the recent updates in the manufacturing of polypeptide and preparation of EPP-DDS based on green biochemical engineering and/or synthetic processes for cancer therapy, including chemotherapy, immunotherapy, photodynamic therapy (PDT), gene therapy, and combination therapy. Then, we surveyed the research progress of inflammation-mediated cancer treatment strategies based on EPP-DDS with high anti-inflammation activity. Finally, we concluded the discovery and green production process of engineered polypeptide, challenges, and perspectives of EPP-DDS. Overall, the EPP-DDS has great potential for cancer therapy in the clinic with improved therapeutic efficacy and reduced adverse effect, which needs the innovation of green biochemical engineering for customized design and production of polypeptides.