Endogenous Protein‐Modified Gold Nanorods as Immune‐Inert Biomodulators for Tumor‐Specific Imaging and Therapy

Abstract Engineered modifications of nanomaterials inspired by nature hold great promise for disease‐specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy. The results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection of immune responses in vivo. Tumor‐specific eP@Au NRs exhibit a dual‐modal imaging capability and trigger a mild photothermal effect under near‐infrared light irradiation, enabling highly efficient imaging and therapy of tumors. Transcriptome sequencing and confirmatory experiments reveal that the antitumor effect is mainly attributed to the repression of PI3K‐Akt/MAPK signaling pathways at the molecular level. This powerful and surprising in situ eP‐regulated biomodulation demonstrates the advantages of convenient fabrication, inert immunogenicity, and biocompatibility, providing an alternative strategy for biomedical imaging and therapy.