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- Heavenly Bodies: Golden nanostars have become a double weapon against cancer
Heavenly Bodies: Golden nanostars have become a double weapon against cancer
Russian researchers have taught golden nanostars to find cancer cells using special proteins that recognize the characteristic carbohydrate structures on their surface. This approach made it possible to provide targeted delivery of nanoparticles to the tumor and use them simultaneously for diagnosis and photothermal therapy. The same nanostar first helps to see the tumor, and then destroys it from heating without a scalpel and without drugs. The technique looks promising, especially for the treatment of tumors with an atypical molecular profile, oncologists told Izvestia. However, the research is still at the preclinical stage, and it is necessary to wait for the results of the full test cycle.
The search for tumor cells by their "sugar passport"
MIPT scientists have developed a method for targeting cancer cells using gold nanostars, the surface of which has been modified with lectins, proteins capable of recognizing specific carbohydrate structures. This was reported to Izvestia by the press service of the Ministry of Education and Science.
The technology provides a targeted accumulation of such stars in the tumor area and opens up the possibility of combining the diagnosis of neoplasms with their photothermal treatment.
Gold nanostars decorated with lectins for cancer theranostics: imaging of tumors and photothermal therapy
— In summer, we look for stars in the sky, but here it's the other way around: the golden nanostars had to find their target on their own — the tumor. Lectins, which recognize a kind of "sugar passport" of cancer cells, became their navigator. After reaching the tumor, the nanostars, under the influence of near-infrared radiation, turn light into heat and destroy tumor cells. It turned out almost as in the title of our article: Shine first, then fight," said Victoria Shipunova, head of the research and Laboratory of Biochemical Research of Carcinogenesis at MIPT.
The work of the scientific group relates to theranostics— an approach that combines the diagnosis and therapy of tumors within a single platform. One of the main tasks in creating such systems is to teach the drug to distinguish cancer cells from healthy ones and accumulate exactly where its action is required. For this purpose, molecular targets are used, which serve as a kind of "address" of the tumor.
Different types of cancer have a different set of such targets. For example, when choosing breast cancer therapy, three key markers are taken into account: the estrogen (ER) and progesterone (PR) receptors, as well as the human epidermal growth factor type 2 (HER2) receptor. However, in triple-negative breast cancer, ER and PR are not expressed, and HER2 overexpression is absent. Therefore, standard targeted therapies targeting these targets are inapplicable, and researchers have to look for other molecular landmarks on the surface of tumor cells.
— If a tumor does not have the usual protein targets, this does not mean that it becomes invisible. In malignant degeneration, not only the set of protein receptors changes, but also the composition of carbohydrate structures on the cell surface. Our idea was to recognize these changes using lectins and use them as guides for targeted delivery of nanoparticles. This approach is especially important for tumors that lack classical therapeutic targets," explained Victoria Shipunova.
To solve this problem, MIPT scientists have created a theranostic agent based on gold nanostars. Their surface was modified with lectins capable of recognizing characteristic carbohydrate structures on tumor cells. They ensure targeted delivery and retention of nanoparticles in the tumor, and gold nanostars absorb laser radiation and convert it into heat, allowing visualization and destruction of tumor tissue.
Testing of gold nanostars on mice
The scientists conducted experiments on mice with solid (solid) tumors. Using optical tomography, the researchers traced the path of the fluorescently labeled particles in the body and made sure that they reach the tumor and accumulate in it. As in the case of many other nanoparticles, a significant part of the gold nanostars remained in the liver — up to 46%. At the same time, about 20% of the recorded signal accounted for the tumor, which turned out to be sufficient for a pronounced therapeutic effect.
Visualization of tumors using gold nanostars (AuNS) decorated with lectins and labeled with Cy7 dye. AuNS-lectin was injected intravenously into mice and imaging was performed using the LumoTrace FLUO bioimage system. Effective tumor contrast is observed only for AuNS-SBA particles
After the nanostars accumulated in the tumor, it was irradiated with a laser in the near infrared range. The particles absorbed light and turned it into heat: the temperature of the tumor increased by several degrees, while the surrounding healthy tissues practically did not heat up.
The result was impressive: after one injection and one photothermal therapy procedure, by the 18th day of the experiment, tumor growth suppression reached 100%. In other words, targeted delivery allowed the nanostars to perform both tasks: first to identify the location of the tumor, and then to target it with light.
— Today, targeted delivery of antitumor agents is most often associated with monoclonal antibodies that recognize protein receptors. However, the surface of the tumor cell contains not only protein, but also carbohydrate targets. We have shown that lectins can act as effective targeting molecules and ensure the delivery of nanoparticles to the tumor by recognizing the altered glycosylation profile. This approach does not replace antibodies, but significantly expands the set of tools for creating targeted systems, especially for tumors without suitable protein targets," said Victoria Shipunova.
The prospect of using gold nanostars
The platform proposed at MIPT solves one of the key problems of modern oncology — the treatment of tumors with an atypical molecular profile, a professor of the faculty group at the Scientific and Educational Center at the B.V. Petrovsky Russian National Research Medical Center, head of the Department of antitumor Drug Therapy at Clinical Hospital No. 1 of Medsi Group of Companies, a doctor, told Izvestia.- oncologist and chemotherapist Anastasia Mochalova.
— The main advantages of the approach are high selectivity (particles distinguish the tumor from healthy vascular endothelium), rapid internalization into cells and a pronounced photothermal effect in the near infrared range. The method will be in maximum demand in the targeted therapy of patients for whom standard protocols are powerless due to the lack of classical targets, in particular for triple-negative breast cancer," the specialist noted.
In the proposed approach, the same nanostar first helps to see the tumor, and then destroys it due to heat exposure without a scalpel and without drugs, explained NTI expert on new materials and technologies Evgeny Vishnevsky.
"The difficulty may probably be that nanostars should be as uniform in shape as possible, otherwise they will warm up in different ways, and in any case, light penetrates only a few centimeters into the body, so the method is primarily suitable for tumors on the surface or in easily accessible places," said the expert.
This is a promising approach, because usually the diagnosis and treatment of tumors are carried out separately, by different means, but here one nanoparticle first helps to see the neoplasm, and then destroys it point-by-point under near-infrared light, without the systemic toxicity inherent in chemotherapy, said Marina Chumakova, a leading market expert at NTI Healthnet. But you need to understand that this is still a preclinical level and it remains to be studied how gold behaves in the body during accumulation.
The article was published in the European Journal of Pharmacy and Biopharmaceutics. The work was carried out with the support of the Russian Science Foundation.
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