Polypeptide Bilayer Assembly-Mediated Gene Delivery Enhances Chemotherapy in Cancer Cells.

Developing gene vectors with high transfection efficiency and low cytotoxicity to humans is crucial to improve gene therapy outcomes. This study set out to investigate the use of cationic polypeptide bilayer assemblies formed by coil-sheet poly(l-lysine)-block-poly(l-benzyl-cysteine) (PLL-b-PBLC) as gene vectors that present improved transfection efficiency, endosomal escape, and biocompatibility compared to PLL. The formation of the polyplexes was triggered by hydrogen bonding, hydrophobic interactions, and electrostatic association between the cationic PLL segments and the negatively charged plasmid encoding p53, resulting in self-assembled polypeptide chains. Transfection efficiency of these polyplexes increased with increments of PLL-to-PBLC block ratios, with PLL15-b-PBLC5 bilayers exhibiting the best in vitro transfection efficiency among all, suggesting that PLL-b-PBLC bilayer assemblies are efficient in the protection and stabilization of genes. The polypeptide bilayer gene vector reversed the cisplatin sensitivity of p53-null cancer cells by increasing apoptotic signaling. Consistent with in vitro results, mouse xenograft studies revealed that PLL15-b-PBLC5/plasmid encoding p53 therapy significantly suppressed tumor growth and enhanced low-dose cisplatin treatment, while extending survival of tumor-bearing mice and avoiding significant body weight loss. This study presents a feasible gene therapy that, combined with low-dose chemotherapeutic drugs, may treat genetically resistant cancers while reducing side effects in clinical patients.

Antibacterial Gelatin Composite Hydrogels Comprised of In Situ Formed Zinc Oxide Nanoparticles.

We report the feasibility of using gelatin hydrogel networks as the host for the in situ, environmentally friendly formation of well-dispersed zinc oxide nanoparticles (ZnONPs) and the evaluation of the antibacterial activity of the as-prepared composite hydrogels. The resulting composite hydrogels displayed remarkable biocompatibility and antibacterial activity as compared to those in previous studies, primarily attributed to the uniform distribution of the ZnONPs with sizes smaller than 15 nm within the hydrogel network. In addition, the composite hydrogels exhibited better thermal stability and mechanical properties as well as lower swelling ratios compared to the unloaded counterpart, which could be attributed to the non-covalent interactions between the in situ formed ZnONPs and polypeptide chains. The presence of ZnONPs contributed to the disruption of bacterial cell membranes, the alteration of DNA molecules, and the subsequent release of reactive oxygen species within the bacterial cells. This chain of events culminated in bacterial cell lysis and DNA fragmentation. This research underscores the potential benefits of incorporating antibacterial agents into hydrogels and highlights the significance of preparing antimicrobial agents within gel networks.