Researchers have discovered that squid ink – a black suspension sprayed by cuttlefish to prevent predators – contains nanoparticles that strongly inhibit the growth of cancerous tumors in mice. The nanoparticles mainly consist of melanin, amino acids, monosaccharides (simple sugars), metals and other compounds. The researchers showed that the nanoparticles can modify the immune function in tumors and, when combined with radiation, can almost completely inhibit tumor growth.
The researchers, led by Wuhan University's Renmin Hospital's Pang-Hu Zhou and Wuhan University's Chemistry Institute Xian-Zheng Zhang, have an article on the ability of nanoparticles from cuttlefish to increase tumor growth in a inhibit, published recently published edition of ACS Nano .
"We have found natural nanoparticles of cuttlefish ink with good biocompatibility that can simultaneously deliver tumor immunotherapy and photothermal therapy," Zhang told Phys.org . "This finding may stimulate research into natural materials for medical applications."
Tumor immunotherapy involves combating cancer by stimulating the body's immune system. One strategy is to target leukocytes or white blood cells. Macrophages are the predominant leukocytes in some tumors and can take one of two forms: M1 or M2. The M1 phenotype engulfs and destroys tumor cells through the process of phagocytosis and through the activation of T cells (other white blood cells). In the M2 phenotype, however, this immune function is suppressed, so that the tumor growth can continue unhindered. In tumor environments, the M2 phenotype almost always outweighs the M1 phenotype.
More recently, researchers have been working on the development of small molecules and antibodies capable of converting M2 macrophages into M1 macrophages. At the same time, they are developing nanoparticles, such as photothermal agents, which locally destroy cancer cells by thermal ablation when irradiated. These agents can be integrated into synthesized nanoparticles and potentially administered to patients. A disadvantage, however, is that these synthetic nanoparticles are expensive and require complicated manufacturing processes.
Because of these costs, some researchers have chosen alternatives for nature. Previous research has shown that certain natural compounds, including those found in brown algae and some bacteria, contain polysaccharides that can reprogram M2-type macrophages into the M1 type.
In the new work, the researchers found that cephalopod nanoparticles that are spherical and about 100 nm in diameter also have this ability. After confirming the biocompatibility of these nanoparticles, the researchers performed several experiments on both in vitro with tumor cells and in vivo with tumor-challenged mice. In experiments in vitro the researchers found that irradiation of the nanoparticles with near-infrared irradiation killed approximately 90% of the tumor cells, although the nanoparticles showed almost no cytotoxicity without irradiation. The researchers explained that the high melanin content of the nanoparticles plays a key role in the irradiation process, since melanin has a good photothermal conversion capability.
In mice, nanoparticle treatment was effective both alone and in combination with radiation. although the irradiation further improved the result. Bioluminescence imaging revealed that treated mice had significantly less tumor bioluminescence compared to controls, indicating greatly reduced metastasis of the internal organs. Mice treated with both nanoparticles and radiation showed almost complete inhibition of tumor growth.
Using gene analysis, the researchers identified 194 differentially expressed genes involved in immune functions associated with the regulation of inflammatory response and cell death. and that were either regulated up or down by the treatment. The analysis revealed that a particular signaling pathway is responsible for the conversion of M2 macrophages into M1 macrophages. This mechanism not only leads to phagocytosis of tumor cells, but also stimulates the immune system to produce various anti-tumor factors, all of which play a role in inhibiting tumor growth.
In the future, researchers want to explore other natural materials that have anti-cancer properties.
"Our research team is currently investigating the biomedical potential of natural materials such as hair, cuttlefish, bacteria, fungi, and even the cells of the human body as a therapeutic drug carrier," Zhang said. "By being inspired by nature and using its own properties, we expect valuable research that delivers new and effective solutions to treat clinical diseases."
Elegant antibody nanoparticles override the immunological tolerance of tumors
Rong-Hui Deng. Mei-Zhen-Zou, Diwei Zheng, Si Yuan Peng, Wenlong Liu, Xue Feng Bai, Han Shi Chen, Yunxia Sun, Pang Hu Zhou and Xian Zheng Zhang. "Octopod ink nanoparticles inhibit tumor growth by synergizing immunotherapy and photothermal therapy." ACS Nano . DOI: 10.1021 / acsnano.9b02993
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Cuttlefish ink found promising for cancer treatment (2019, July 22)
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