Protein Nanotherapeutics as an Emerging Modality for Cancer Therapy

Protein drugs are a unique and versatile class of biotherapeutics that have not only high biological activity but also superb specificity. This rapidly evolving biotechnology has rendered it possible to produce various proteins in a large scale and reproducible way. Many proteins have demonstrated striking anticancer activities and have emerged as advanced alternatives to cytotoxic chemotherapeutic agents for cancer therapy. The clinical translation of anticancer proteins with intracellular targets is, nevertheless, severely hindered by their fast degradation in vivo, poor cell penetration, and inefficient intracellular transportation. The past few years have witnessed tremendous effort and progress in developing polymeric protein delivery nanosystems, ranging from nanoparticles, nanocapsules, nanogels, micelles, to polymersomes, for the treatment of different tumors such as lung tumors, breast tumors, ovarian cancers, and glioblastoma. These proof‐of‐concept studies point out that protein nanotherapeutics, with rationally designed nanovehicles, are able to overcome the extracellular barriers, cell membrane barriers, and intracellular barriers, and systemically deliver proteins into targeted cancer cells, resulting in effective cancer protein therapy. Protein nanotherapeutics appear to be a novel modality for safe and efficient cancer treatment.