Targetable Biomimetic NIR-II Theranostic Nanoplatform for Highly Efficient Multimodal Imaging-Guided Photothermal Therapy of Cervical Cancer

Chenyang Chu,1,2,* Zhong Du,3,* Jing Wang,1,2 Maierhaba Aili,1,2 Jiaxing Li,4 Jiabao Xiong,3 Rong Ma,1,2 Cailing Ma,1,2 Nuernisha Alifu5 1Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, People’s Republic of China; 2Xinjiang Key Laboratory of Medical Animal Model Research, Xinjiang Medical University, Urumqi, People’s Republic of China; 3The Second Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi, People’s Republic of China; 4School of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, People’s Republic of China; 5Science and Technology Innovation and Achievement Transformation Service Center, Xinjiang Medical University, Urumqi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cailing Ma, Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830054, People’s Republic of China, Email [email protected] Nuernisha Alifu, Science and Technology Innovation and Achievement Transformation Service Center, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China, Email [email protected]: Cervical cancer (CC) is still the fourth most common cause of cancer deaths in women. However, current biomedical imaging techniques exhibit inherent limitations in the diagnosis and treatment of CC. This study aims to develop a biomimetic nanoplatform based on tumor cell membranes, loaded with a palladium (Pd)-based computed tomography (CT) contrast agent and the near-infrared (NIR) fluorescent probe indocyanine green (ICG). This multifunctional nanoplatform is designed to integrate multimodal imaging with photothermal therapy (PTT), thereby improving the diagnostic accuracy and therapeutic efficacy against CC.Methods: In this study, biomimetic nanoparticles (NPs), designated as M@Pd-ICG NPs, were synthesized by encapsulating Pd and ICG within HeLa cell membranes derived from cell-derived xenograft (CDX) models. Subsequently, the toxicity, biocompatibility, and tumor suppression capability of the M@Pd-ICG NPs were evaluated in vitro. In vivo, the multimodal imaging performance of the M@Pd-ICG NPs and their photothermal therapeutic efficacy under 808-nm laser irradiation were investigated in mouse model bearing subcutaneous cervical tumor.Results: The M@Pd-ICG NPs were successfully prepared and exhibited favorable stability, excellent photothermal conversion efficiency (34.04%), and good biocompatibility, enabling homologous targeting and prolonged circulation time. The M@Pd-ICG NPs integrated the complementary advantages of NIR-II fluorescence imaging (900– 1700 nm, NIR-II FI), photothermal imaging (PTI), and CT imaging. Both in vitro and in vivo studies demonstrated that, under 808-nm laser irradiation, M@Pd-ICG NPs induced significant photothermal effects and tumor ablation.Conclusion: M@Pd-ICG NPs successfully integrate multimodal imaging and PTT, owing to their excellent targeting capability and good biocompatibility, demonstrating potential for further biomedical applications.Keywords: cervical cancer, tumor cell membranes, palladium, indocyanine green, multimodal imaging, photothermal therapy