2. Academic Validation
  3. Near-infrared light-induced photothermal and immunotherapy system for lung cancer bone metastasis treatment with simultaneous bone repair

Near-infrared light-induced photothermal and immunotherapy system for lung cancer bone metastasis treatment with simultaneous bone repair

  • Bioact Mater. 2025 Jun 10:52:182-199. doi: 10.1016/j.bioactmat.2025.06.008.
Guoqing Zhong 1 2,  Yali Miao 3,  Jielong Zhou 4 1 2,  Yijie He 1 2,  Wenjie Yang 1 2,  Chongquan Huang 1 2,  Yunhui Zhang 1 2 4,  Jin Xiao 1 2,  Bingqing Bai 1 4,  Jiaqi Zhou 1 2,  Renshan Li 1 2,  Tiantian Wei 1 2,  Yu Zhang 1 2,  Shi Cheng 1 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
  • 2 Guangdong Engineering Technology Research Center of Functional Repair of Bone Defects and Biomaterials, Guangzhou, 510080, China.
  • 3 School of Chemical Engineering and Technology, Guangdong Industry Polytechnic University, Guangzhou, 510300, China.
  • 4 School of Medicine South China University of Technology, Guangzhou, 510080, China.
PMID: 40538765 DOI: 10.1016/j.bioactmat.2025.06.008
Abstract

Approximately half of lung Cancer patients experience bone metastasis, leading to bone loss, fracture, and Other skeletal-related events. Although immunotherapies have significantly advanced the therapeutic landscape for lung Cancer, bone metastases have an immunologically "cold" microenvironment, representing a challenging obstacle when treating lung Cancer. The combination of immunotherapy and photothermal therapy (PTT) for treating tumor-induced bone defects holds promise for enhancing the efficacy of local tumor ablation and inhibiting tumor recurrence and metastasis through activating systemic immune responses. Herein, we developed an injectable hydrogel-based photothermal immunotherapy system (BP@Gel-CD[SA] hydrogel) incorporating STING agonists (SA) and black phosphorus nanosheets (BPNSs) for high-efficiency tumor elimination, immune activation, and bone regeneration. The photothermal and photodynamic activities of BPNSs induce hyperthermia and ROS-mediated Apoptosis of tumor cells. Meanwhile, SA loaded into the nano-boxes in BP@Gel-CD[SA] hydrogel by host-guest interaction significantly activates the cGas-STING pathway. It stimulates immunogenic cell death (ICD), synergistically promoting immune cell infiltration. Single-cell RNA sequence analysis confirms the modulation of the tumor microenvironment (TME) through the PTT-mediated ICD effect and the transactivation of the cGAS-STING pathway in immune cells of the TME. More importantly, the system can significantly inhibit the growth of distant tumors via systemic immune activation and elicit long-term immune memory in addition to tumor eradication. In the long term, this hydrogel system can promote the formation of new bone at sites of tumor-induced bone destruction, improving bone strength in the affected area. Collectively, this strategy provides an effective and safe option for treating lung Cancer bone metastases.

Keywords

Black phosphorus; Bone metastasis; Photothermal immunotherapy; STING activation.

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