Targeted photothermal therapy of mice and rabbits realized by macrophage-loaded tungsten carbide
Yan Gao1, Weicheng Huang2, Chunyu Yang1
1School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China. xuyanling@hit.edu.cn chongshenguo@hit.edu.cn.
Abstract:
Although great advances have been made in photothermal therapy, the efforts hitherto have mainly achieved antitumor effects in mice with a subcutaneous tumor model, which is less clinically relevant. Therefore, it is very urgent to make further progress in investigating the possibility of larger animal models with orthotopically xenografted tumors for further clinical trials. Herein, macrophage-loaded tungsten carbide has been employed for the photothermal ablation of orthotopic breast tumors in rabbits in a targetable way. Tungsten carbide as an excellent photoactive material can induce on-site hyperthermia and even reactive oxygen species for tumor destruction; meanwhile, the macrophage is a biocarrier that behaves as a "Trojan horse" for tumor targeting. Both experimental results and theoretical simulations verified the broadband photoabsorption of WC. The WC loaded in the macrophages readily maintains the photothermal and photodynamic effects of the bare WC, while its accumulation at the tumor site is nearly 10 times that of bare WC. As such, the complete removal of solid tumors in rabbits was confirmed with the aid of B-mode ultrasound and contrast-enhanced ultrasound surveillance. Apparently, this work advances photothermal therapy one step further to large animal models with orthotopic tumors.
Insights
This study introduces macrophage-loaded tungsten carbide (WC) for targeted photothermal therapy in large animal models. This approach effectively destroyed orthotopic breast tumors in rabbits, advancing cancer treatment research.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Photothermal therapy (PTT) shows promise for cancer treatment but is limited to small animal models.
- Clinically relevant studies require larger animal models with orthotopic tumors.
- Developing targeted delivery systems is crucial for enhancing PTT efficacy.
Purpose of the Study:
- To investigate the efficacy of macrophage-loaded tungsten carbide (WC) for targeted photothermal ablation of orthotopic breast tumors in rabbits.
- To evaluate WC's photothermal and photodynamic properties when encapsulated within macrophages.
- To establish a more clinically relevant large animal model for PTT.
Main Methods:
- Tungsten carbide (WC) nanoparticles were loaded into macrophages.
- Macrophage-loaded WC was administered to rabbits with orthotopic breast tumors.
- Photothermal ablation was performed using near-infrared irradiation.
- Tumor ablation was monitored using B-mode and contrast-enhanced ultrasound.
- Theoretical simulations verified WC's photoabsorption properties.
Main Results:
- Macrophage loading significantly enhanced WC accumulation at the tumor site (nearly 10-fold increase compared to bare WC).
- Macrophage-encapsulated WC retained potent photothermal and photodynamic therapeutic effects.
- Complete eradication of orthotopic breast tumors was achieved in rabbits.
- Ultrasound imaging confirmed tumor destruction and absence of recurrence.
Conclusions:
- Macrophage-mediated delivery of tungsten carbide nanoparticles represents a promising strategy for targeted photothermal therapy in large animal models.
- This approach overcomes limitations of traditional PTT by enhancing tumor targeting and efficacy.
- The study provides a foundation for future clinical translation of advanced photothermal therapies.
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