DOI: 10.1002/adfm.78549 ISSN: 1616-301X

Hydrogen Selenide Gas Therapy Integrated With NIR‐II Multimodal Imaging for Precision Theranostics of Cervical Cancer

Zhong Du, Jiabao Xiong, Chenyang Chu, Yuxiang Gao, Haiyang Wang, Meihaguli Abulaizi, Siyu Huang, Kaikai Ma, Chi Zhang, Maierhaba Aili, Nuernisha Alifu, Biao Dong

ABSTRACT

Cervical cancer treatment is hindered by drug resistance, systemic toxicity, and poor real‐time monitoring of therapy. Herein, we present an intelligent nanotheranostic platform, recombinant human serum albumin (rHSA)‐indocyanine green (ICG)‐Bi 2 (SeO 3 ) 3 (HIB) based on hydrogen selenide (H 2 Se) gas therapy and multimodal imaging. In response to high glutathione (GSH) levels in the tumor microenvironment and under 808 nm laser irradiation, HIB NCs achieve on‐demand H 2 Se release, which sensitizes photothermal/photodynamic therapy and promoted autophagy by regulating heat shock proteins 70 (HSP70) and oxidative stress pathways, as validated by bioinformatics. Distinct from conventional gas agents, HIB NCs enable real‐time, non‐invasive dynamic monitoring of H 2 Se distribution and therapeutic responses using an integrated near‐infrared II (900–1700 nm, NIR‐II) fluorescence/computed tomography (CT)/photoacoustic (PA)/laser speckle contrast imaging (LSCI) multimodal strategy, overcoming the lack of in vivo H 2 Se sensing. In the cervical cancer lymph node metastasis model, HIB NCs could identify diseased lymph nodes more quickly for tracing and exhibit good biocompatibility. This study explored H 2 Se as a potent anti‐metastatic gas messenger and constructed a clinically translatable platform that combines precise gas release, multimodal dynamic monitoring, and synergistic phototherapy.