A light-driven molecular motor-polypeptide conjugate supports controlled cell uptake.

While light-driven molecular motors (MMs) hold immense potential to control cell function, low biocompatibility and solubility have hampered their implementation. We developed a novel polypeptide-conjugated MM by linking a propargyl-derivatized light-driven MM to a poly-L-glutamic acid-based carrier (P) with inherent mitochondria tropism through click chemistry, denoted P-MM. P-MM effectively maintained the parental stability and unidirectional rotational capabilities of MM upon irradiation at 405 nm. Light-induced supramolecular conformational changes significantly increased cell uptake compared to non-irradiated controls while retaining the subcellular targeting capacity of P. P-MM exhibited minimal cytotoxicity and reactive oxygen species production, suggesting a non-disruptive interaction with cell membranes. Overall, we establish a connection between irradiation and enhanced biological responses, demonstrating the potential of integrating MMs with targeted polymeric nanocarriers for controlled, light-responsive behavior in biological systems and innovative applications in advanced therapeutic/diagnostic strategies.