Synthetic polypeptides from the ring-opening polymerization of N-carboxyanhydrides (NCAs) are one of the most important biomaterials. The unique features of these synthetic polypeptides, including their chemical diversity of side chains and their ability to form secondary structures, enable their broad applications in the field of gene delivery, drug delivery, bio-imaging, tissue engineering, and antimicrobials. In this review article, we summarize the recent advances in the design of polypeptide-based supramolecular structures, including complexes with nucleic acids, micelles, vesicles, hybrid nanoparticles, and hydrogels. We also highlight the progress in the chemical design of functional polypeptides, which plays a crucial role to manipulate their assembly behaviours and optimize their biomedical performances. Finally, we conclude the review by discussing the future opportunities in this field, including further studies on the secondary structures and cost-effective synthesis of polypeptide materials.

Photodynamic therapy (PDT) is considered a promising approach for the treatment of cancer and is achieved via the photosensitizer (PS)-mediated incomplete reduction of oxygen upon light irradiation, which generates high levels of reactive oxygen species (ROS) to induce potent vascular damage and to directly kill tumor cells. However, there is an undesirable impediment with this approach in that tumor tissues generally suffer from serious hypoxia, which significantly affects the efficiency of PDT. Additionally, PDT that consumes oxygen will further aggravate tumor hypoxia, thus potentially leading to multiple undesirable consequences, such as angiogenesis, tumor invasiveness, and tumor metastasis. This mini-review provides a comprehensive overview of the recent research progress on overcoming or utilizing tumor hypoxia to enhance the therapeutic efficacy of PDT.

Significance: Delivery remains a significant challenge for robust implementation of CRISPR/Cas9. We report an efficient CRISPR/Cas9 delivery system comprising PEGylated nanoparticles based on the α-helical polypeptide PPABLG. Assisted by the high membrane-penetrating ability of the polypeptide, P-HNPs achieved efficient cellular internalization and endosomal escape. The CRISPR/Cas9 delivery system could reach 47.3% gene editing in cells, 35% gene deletion in vivo, and HeLa tumor growth suppression >71%, demonstrating an advantage over the existing conventional polycationic transfection reagents. Efficient also in knock-in and gene activation, the reported CRISPR/Cas9 delivery system serves to advance gene editing in vitro and in vivo.