Secondary Structure-Guided Assembly of Uniform Disk-Like Polymeric Micelles Incorporating Hydrophobic Platinum Drugs for Improved Tumor Targeting

Tailoring the secondary structure of a poly(amino acid) offers a powerful approach for precisely assembling nanostructures for biomedical applications. In this study, we demonstrated that the poly(α-l-glutamic acid) segment of the poly(ethylene glycol)-poly(α-l-glutamic acid) block copolymer forms an α-helix structure through complexation with (1,2-diaminocyclohexane)platinum(II) (DACHPt). This α-helix induction was crucial for controlling the kinetics of micelle formation from DACHPt-complexed poly(ethylene glycol)-poly(α-l-glutamic acid) block copolymers, resulting in the formation of disk-like polymeric micelles with a narrowly distributed size of approximately 30 nm. In contrast, block copolymers with a racemic poly(d,l-glutamic acid) segment, which does not form an α-helix, produced nonuniform, elongated micelles. These findings indicate that the α-helix structure in the block copolymer is key to regulating the micelle size and shape. Furthermore, the α-helices within the micelle structure significantly enhanced the stability of the micelles in the bloodstream by retarding the disintegration mediated by chloride ions. This increased stability led to the effective accumulation and enhanced antitumor activity of DACHPt-complexed micelles against pancreatic tumors.