Self-assembled protein-aptamer nanoparticles for targeted cancer immunotherapy.

Developing effective delivery methods for therapeutic proteins poses a major challenge in oncology. Protein drugs offer targeted mechanisms against tumor cells, minimizing off-target effects and potential for personalized therapy. Our study proposes a controllable in situ self-assembly strategy to construct FimH protein-based nanoparticles incorporating mIFP protein and PD-L1 aptamer, demonstrating potential for targeted protein delivery and tumor therapy. The PD-L1 aptamer exerts its effect by disrupting immune checkpoints, thereby modulating immune checkpoints and promoting immune cell activity, ultimately enhancing anti-tumor responses. The FimH protein plays a role in immune activation, which may promote T cell responses and further enhances in vivo tumor suppression. Furthermore, doxorubicin (DOX) induces tumor cell apoptosis, and its combination with immunotherapy results in a synergistic attack on the tumor. The self-assembled nanoparticles facilitate the efficient transport of therapeutic proteins to the tumor site, thereby mitigating renal clearance and enzymatic degradation in vivo. Additionally, the presence of mIFP enables in vivo imaging. In murine models, PD-L1 aptamer-protein nanoparticles suppressed primary colorectal tumors and inhibited distant, untreated tumors. This controlled formation of protein nanoparticles for targeted delivery offers a versatile platform for protein-based tumor therapies.