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Beibei Ma,1,* Jie Sheng,1,2,* Ping Wang,1 Zhongying Jiang,1,2 Entomack Borrathybay31College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, People’s Republic of China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, People’s Republic of China; 3College of Biology and Geography Sciences, Yili Normal University, Yining, Xinjiang, 835000, People’s Republic of China*These authors contributed equally to this work Background: Tumor metastasis is responsible for most cancer death worldwide, which lacks curative treatment.Purpose: The objective of this study was to eliminate tumor and control the development of tumor metastasis.Methods: Herein, we demonstrated a smart nano-enabled platform, in which 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2h-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) and tirapazamine (TPZ) were co-loaded in poly(ϵ-caprolactone)-poly(ethylene glycol) (PEG-PCL) to form versatile nanoparticles (PEG-PCL-IR780-TPZ NPs).Results: The intelligence of the system was reflected in the triggered and controlled engineering. Specially, PEG-PCL not only prolonged the circulation time of IR780 and TPZ but also promoted tumor accumulation of nanodrugs through enhanced permeability and retention (EPR) effect. Moreover, reactive oxygen species (ROS) generated by IR780 armed by an 808 nm laser irradiation evoked a cargo release. Meanwhile, IR780, as a mitochondria-targeting phototherapy agent exacerbated tumor hypoxic microenvironment and activated TPZ for accomplishing hypoxia-activated chemotherapy. Most significantly, IR780 was capable of triggering immunogenic cell death (ICD) during the synergic treatment. ICD biomarkers as a “danger signal” accelerated dendritic cells (DCs) maturation, and subsequently activated toxic T lymphocytes.Conclusion: Eventually, antitumor immune responses stimulated by combinational phototherapy and hypoxia-activated chemotherapy revolutionized the current landscape of cancer treatment, strikingly inhibiting tumor metastasis and providing a promising prospect in the clinical application.Keywords: phototherapy, hypoxia-activated chemotherapy, IR780, tirapazamine, antitumor immune responsive, metastasis

Jie Sheng,1,2 Beibei Ma,1 Qian Yang,1 Chao Zhang,2 Zhongying Jiang,1,2 Entomack Borrathybay3 1College of Electronic and Information Engineering, Yili Normal University, Micro-nano Electric Sensing Technology and Bionic Devices Key Laboratory, Yining 835000, China; 2Physics School of Nanjing University, Laboratory of Solid State Microstructures, Nanjing 210093, China; 3College of Biology and Geography Sciences, Yili Normal University, Yining 835000, Xinjiang, China Introduction: In recent years, near-infrared laser-induced photothermal therapy is being considered as a promising approach to kill tumors owing to its noninvasive nature and excellent antitumor efficiency. However, the lack of ideal photothermal agents hinders further development of this technology. Materials and methods: Aiming at solving this long-standing obstacle, we report here about the polyethylene glycol (PEG)-DA modified copper sulfide (CuS) nanoparticles (NPs) (PEG-DA-CuS NPs), a kind of semiconductor photothermal agents that show excellent photothermal stability and high heat conversion efficiency. Results and discussion: Owing to the surrounding PEG, the water solubility of CuS NPs was significantly improved when circulating in blood in the body. When the NPs reached the tumors and were irradiated by a 1,064 nm laser (1 W/cm2, 10 minutes), the local temperature increased above 90°C, triggering the retro Diels–Alder reaction. After the release of PEG chain, CuS NPs soon formed aggregates and enriched the tumor via the enhanced permeability and retention effect, promoting the efficacy of photothermal therapy. Conclusion: Therefore, we believe PEG-DA-CuS NPs are able to serve as a kind of cytotoxic and efficient photothermal agent to kill cancer. Keywords: CuS, PEG, retro Diels–Alder reaction, excellent photothermal stability, high heat conversion efficiency, aggregation in tumor