From Nanofibers to Nanorods: Nanostructure of Peptide‐Drug Conjugates Regulated by Polypeptide‐PEG Derivative and Enhanced Antitumor Effect

Abstract Peptide‐drug conjugates (PDCs) are a type of self‐assembled prodrug with good potential for drug delivery due to their excellent biocompatibility, high drug loading, and permanent controllable release. However, most PDCs tend to self‐assemble into filamentous nanostructures in water and under physiological conditions, making them unsuitable as intravenous formulations due to the entanglement of long fibers and the risk of thrombus. Injected PDCs also face challenges in overcoming the complex physiological environment to reach the target site. To expand their clinical use, it is necessary to control the properties of PDC, including the self‐assembled structure and physiological performance, to avoid the above problems. Based on assembly mechanism studies of PDCs, a new method for regulating PDC morphology is developed by controlling intermolecular interactions in the assembly process. This method can alter the final morphology of PDCs from nanofibers to nanorods, and the introduced macromolecules endow the PDC with new characteristics that facilitate stable and high‐efficiency access to the target site.