Successful development of multifunctional liquid metal nanocomposites for cancer photoimmunotherapy

Key Points

• World's first successful development of innovative nanocomposites comprising lactic acid bacteria components and liquid metal
• Selective tumor accumulation via EPR effect with demonstrated visualization and therapeutic efficacy in mouse-transplanted cancers
• Complete cancer elimination through synergistic immune activation and photothermal conversion effects under near-infrared light irradiation
• Confirmed excellent biocompatibility, promising new cancer diagnostic and therapeutic technologies

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A research team led by Professor Eijiro Miyako from the Materials Chemistry Frontiers Research Area at Japan Advanced Institute of Science and Technology (JAIST) (President: Minoru Terano, Nomi City, Ishikawa Prefecture) has successfully developed multifunctional nanocomposites by coating liquid metal^*1 surfaces with lactic acid bacteria^*2 components and near-infrared fluorescent dye (indocyanine green^*3).

The developed nanocomposites demonstrate excellent tumor-targeting capability through the EPR effect^*4, effectively accumulating in tumors of mice transplanted with colorectal cancer. Furthermore, irradiation with highly bio-penetrative near-infrared laser light^*5 achieved multidimensional therapeutic effects:

1. Visualization Diagnosis: Clear visualization of cancer sites through indocyanine green
2. Immunotherapy: Potent immune activation through lactic acid bacteria components
3. Photothermal Therapy: Localized hyperthermia treatment via liquid metal photothermal conversion

The research team successfully achieved complete elimination of transplanted mouse cancers within 5 days by applying near-infrared light irradiation for 5 minutes once daily over 2 days (Figure 1). Comprehensive biocompatibility studies also confirmed the high safety profile of these nanocomposites.

This research breakthrough is expected to lead to the creation of innovative cancer photoimmunotherapy technologies that integrate diagnosis and treatment.

Research Background and Content

Focus on Liquid Metal Nanoparticles

Room-temperature liquid metals composed of gallium-indium (Ga/In) alloys possess excellent biocompatibility and physicochemical properties, attracting worldwide attention for biomedical applications. Professor Miyako's team initiated this research based on the concept that "combining immune-activating substances with liquid metals for selective delivery to cancer sites could achieve potent antitumor effects and integrate diagnosis and treatment using near-infrared light."

Utilization of Intratumoral Bacterial Flora

Recent research has revealed that tumor tissues harbor unique bacterial communities. Professor Miyako's team has previously succeeded in isolating various bacteria from tumors and has been developing cancer treatment technologies utilizing these microorganisms (Previous press releases: "Defeating Cancer with Perfect Coordination!" and "Development of Novel Cancer Treatment Approach 'AUN' Using Two Bacterial Species").

Creation of Innovative Nanocomposites

The research team established a simple fabrication method for spherical nanoparticles by mixing Ga/In liquid metal, lactic acid bacteria components, and indocyanine green, followed by ultrasonic treatment. The nanocomposites produced through this method demonstrated the following characteristics:

• High Stability: Maintained particle size stability for over 7 days
• Excellent Cell Compatibility: High membrane permeability with no toxicity
• Efficient Photothermal Conversion: Heat generation capability under near-infrared light irradiation

Demonstration of Outstanding Therapeutic Efficacy

In evaluation experiments using colorectal cancer-transplanted mice, 24 hours after tail vein administration of the nanocomposites, irradiation with 740-790 nm near-infrared light revealed clear fluorescent emission exclusively from cancer sites, confirming selective tumor accumulation via the EPR effect (Figure 2A).

Subsequently, 808 nm near-infrared light irradiation of the accumulated sites (5 minutes every other day for a total of 2 treatments) achieved complete cancer elimination within 5 days through synergistic effects of immune activation and photothermal conversion (Figure 2B).

Control Experiment Results:

• Lactic acid bacteria alone: Demonstrated moderate antitumor effects through immune activation
• Immune-inactive nanoparticles (PEG-phospholipid complex^*6 coated): No significant antitumor effects after laser irradiation

These results clearly demonstrate that the synergistic effects of immune activation by lactic acid bacteria components and photothermal conversion by liquid metal produce potent antitumor activity.

Confirmation of Excellent Safety Profile

Cytotoxicity Testing: In mouse colorectal cancer cells (Colon26) and human normal fibroblasts (TIG103), cell viability based on mitochondrial activity showed no decline 24 hours after nanocomposite administration, confirming absence of cytotoxicity.

Biocompatibility Testing: Blood tests (1 week) and body weight measurements (approximately 1 month) following mouse intravenous administration revealed minimal adverse effects on living organisms.

Research Significance and Future Prospects

This research demonstrates that the developed nanocomposites can serve as foundational technology for next-generation cancer diagnosis and immunotherapy. Furthermore, it is expected to contribute as a novel technological foundation for material design through interdisciplinary integration of nanotechnology, optics, and immunology across broad research fields.

Moving forward, the team aims to expand applications to other cancer types and conduct further safety and efficacy validation toward clinical applications, striving to realize gentler and more effective cancer treatments for patients.

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Publication Information:
This research is scheduled for publication in the top-tier materials science journal "Advanced Composites and Hybrid Materials" (Springer Nature) on September 19, 2025 (local time).

Research Support:
This research was conducted with support from MEXT KAKENHI Grant-in-Aid for Scientific Research (A) (23H00551), Grant-in-Aid for Challenging Research (Pioneering) (22K18440, 25K21827), Japan Science and Technology Agency (JST) University-originated Startup Ecosystem Co-creation Program (JPMJSF2318), JAIST Transcendent Biomedical DX Research Hub, and JAIST Research Center for Biological Function and Sensing.

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Terminology

^*1 Liquid Metal
Metals that exist in liquid state at or below room temperature. Examples include mercury (melting point: approximately -39°C), gallium (melting point: approximately 30°C), and gallium-indium alloy (melting point: approximately 15°C).

^*2 Lactic Acid Bacteria
A general term for bacteria that have the property of producing lactic acid from sugars. The lactic acid bacteria used in this study were isolated from tumors in Professor Miyako's laboratory.

^*3 Indocyanine Green
A green dye used for liver function testing. When irradiated with near-infrared laser light, it can emit near-infrared fluorescence and generate heat.

^*4 EPR Effect
Microparticles with controlled particle size of 100 nm or smaller do not leak into normal tissues but can reach cancer tissues exclusively through tumor blood vessels and accumulate at affected sites. This phenomenon is called the EPR effect (Enhanced Permeation and Retention Effect).

^*5 Near-Infrared Laser Light
A laser is a laser device that amplifies and emits light, or the light itself. Laser light has excellent directivity and convergence properties and can maintain a constant wavelength of generated light. Light in the near-infrared region, particularly wavelengths of 700-1100 nm, is known to have high biological tissue penetration.

^*6 Polyethylene Glycol-Phospholipid Complex
A chemical compound in which polyethylene glycol is bound to phosphorus-containing lipids (fats). It has the effect of solubilizing lipophilic drugs and is one of the compounds commonly used in drug delivery systems.

 

 

Reference

Title of original paper:	Bacterial-adjuvant liquid metal nanocomposites for synergistic photothermal immunotherapy
Authors:	Nina Sang, Seigo Iwata, Yun Qi, Eijiro Miyako*
Journal:	Advanced Composites and Hybrid Materials
DOI:	10.1007/s42114-025-01434-7

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