Researchers have developed an innovative nanotechnology platform that combines liquid metal with immune-stimulating molecules to create a potent, dual-action treatment for cancer. The novel nanocomposites are engineered to accumulate in tumors, where they can be activated by light to destroy cancer cells directly with heat while simultaneously triggering a powerful immune response to attack the remaining disease. This new method has shown remarkable success in preclinical trials, leading to the complete elimination of tumors in mouse models.
The new technology, developed by a team at the Japan Advanced Institute of Science and Technology (JAIST), merges two promising forms of cancer therapy into a single, versatile nanoparticle. At its core is a gallium-indium liquid metal alloy, which is known for its excellent biocompatibility and ability to convert light into heat. These liquid metal droplets are coated with components derived from lactic acid bacteria, which are potent activators of the immune system. By integrating photothermal therapy and immunotherapy, this approach offers a synergistic strategy that not only provides localized tumor destruction but also stimulates a body-wide, lasting defense against the cancer.
A Hybrid Nanoparticle Design
The foundation of this new therapy is a meticulously engineered nanocomposite. The researchers devised a straightforward fabrication method to create the spherical nanoparticles by mixing the gallium-indium liquid metal with the bacterial components and a near-infrared fluorescent dye, followed by an ultrasonic treatment. This process creates a stable, core-shell-like structure that is readily dispersible in water, overcoming a key challenge of working with liquid metals, which are inherently water-immiscible.
The final nanocomposite demonstrates several key characteristics essential for therapeutic use. It maintains its particle size and stability for over a week and shows excellent compatibility with living cells, with tests indicating high membrane permeability and no toxicity. This favorable safety profile was further confirmed through biocompatibility testing in mice, where blood tests and body weight measurements after administration revealed minimal adverse effects. The inclusion of the dye, indocyanine green, serves a dual purpose: it aids in the efficient conversion of light to heat and allows the nanoparticles to be fluorescent, enabling clear visualization of the cancer sites.
Targeting Tumors with Precision
A critical challenge in cancer therapy is ensuring that treatments affect cancerous tissue while sparing healthy cells. The liquid metal nanocomposites leverage a natural phenomenon to achieve this targeted accumulation. Due to their specific size, the nanoparticles are able to selectively gather in tumor tissues through the Enhanced Permeability and Retention (EPR) effect.
The blood vessels that grow within tumors are often leaky and malformed, with larger pores than those found in healthy tissues. This structural flaw allows nanoparticles of a certain size to pass through the vessel walls and enter the tumor microenvironment. Once inside, they tend to remain, or be retained, because tumors also typically have poor lymphatic drainage. This passive targeting mechanism ensures that the therapeutic agent becomes concentrated precisely where it is needed most, increasing its efficacy against the tumor while minimizing exposure to the rest of the body.
Synergy of Heat and Immunity
The novel treatment unfolds in two distinct but complementary phases once the nanocomposites have accumulated at the tumor site and are exposed to near-infrared laser light. This type of light is used because it can penetrate biological tissues more deeply than other wavelengths.
Photothermal Ablation
The first action is photothermal therapy. The liquid metal core of the nanoparticles, assisted by the indocyanine green dye, efficiently absorbs the near-infrared light and converts it into heat. This rapid, localized temperature increase effectively cooks the cancer cells, causing them to die. This method of thermal ablation offers a high degree of specificity, as the damage is confined to the area illuminated by the laser. This targeted destruction provides the initial blow to the tumor mass.
Immune System Activation
The second, and perhaps more powerful, action is immunotherapy. The components of lactic acid bacteria coated onto the nanoparticles act as a potent immune adjuvant. As the nanoparticles heat up and destroy cancer cells, these dead cells release tumor antigens—molecules that the immune system can recognize as foreign. The presence of the bacterial components at the same site acts as a danger signal, stimulating and marshalling immune cells to the location. This process triggers a robust, targeted immune response against the released antigens, effectively training the body’s own defenses to recognize and eliminate any remaining cancer cells, both at the primary tumor site and potentially elsewhere in the body.
Eliminating Cancer in Preclinical Models
The therapeutic efficacy of the multifunctional nanocomposites was evaluated in mice transplanted with colorectal cancer. The results were highly encouraging. Researchers administered the treatment by irradiating the tumor area with a near-infrared laser for five minutes each day. This short treatment cycle achieved the complete elimination of the cancer within just five days.
Throughout the treatment period, the mice showed no evident side effects, underscoring the biocompatibility of the platform. The combination of direct thermal destruction and subsequent immune activation proved to be a powerful synergistic strategy. The research team, led by Professor Eijiro Miyako, believes the convergence of nanotechnology and immuno-engineering could establish a promising new modality for advancing cancer immunotherapy. This work represents a foundational technology for developing the next generation of cancer diagnostics and treatments that are both highly effective and minimally invasive.