Growth Arrest‐Specific 6‐Enriched Near‐Infrared‐II Nanodecoys for Chemo‐Photothermal Therapy and Preemptive Inhibition of Lung Metastasis in Nasopharyngeal Carcinoma

ABSTRACT Nasopharyngeal carcinoma (NPC) is a highly aggressive malignancy with poor prognosis, and preventing its metastasis remains a major clinical challenge. In this work, we developed a series of biomimetic nanodecoys (NDs) capable of precise diagnosis and effective treatment of NPC while concurrently preventing lung metastasis. The NDs were synthesized via precipitation polymerization to form the thermo‐/pH‐responsive poly( N ‐isopropylacrylamide‐co‐acrylic acid) nanogels (PA NGs), followed by the encapsulation of a newly developed aggregation‐induced emission luminogen (AIEgen) for strong near‐infrared (NIR) fluorescence imaging (FLI) and remarkable photothermal therapy (PTT) performance. In combination with the chemotherapeutic drug doxorubicin (Dox), these NDs achieved effective chemo‐photothermal combinatorial therapy. Triggered by the acidic tumor microenvironment, the NDs could release Dox, and this release could be further accelerated under NIR irradiation. Moreover, we demonstrated that growth arrest‐specific 6 (Gas6)‐camouflaged NDs (PND@Gas6(+) NDs) could function as a prophylactic agent to bind the Axl receptor in both tumor and lung metastatic niches, thereby preemptively blocking the Gas6/Axl axis and preventing tumor deterioration and metastasis. This study presents an innovative strategy that integrates real‐time NIR‐II monitoring and synergistic chemo‐PTT therapy for NPC, while also providing a rational design for metastasis inhibition, offering substantial promise for improving NPC treatment.