Researchers at the RIKEN Pioneering Research Institute in Japan, led by Katsunori Tanaka, have published an experimental approach in Nature Communications that uses carbon monoxide naturally released by cancer cells to manufacture anticancer compounds directly inside them. Laboratory tests suggest the approach could eventually provide a way to attack tumors while reducing harmful side effects associated with conventional cancer treatments.
The research tackles one of the greatest challenges in cancer treatment: destroying malignant cells without causing widespread harm to the body. Traditional chemotherapy can cause serious side effects because its toxic effects are not always limited to tumors. The RIKEN team's strategy instead aims to deliver a relatively harmless compound that becomes active only after entering cancer cells.
The system relies on a metal catalyst called a palladacycle, which is enclosed within a protective carrier made of albumin, a common blood protein. This carrier shields the catalyst from substances such as glutathione that would otherwise deactivate it. When the complex reaches a cancer cell, excess carbon monoxide drives a chemical reaction that produces an organic molecule called phenanthridinone. Certain derivatives of this molecule are already incorporated into anticancer drugs and are toxic to cells.
In laboratory experiments, the team exposed cultured human liver, cervical, breast, and lung cancer cells to the albumin-palladacycle complex for 48 hours. They also tested it on a noncancerous cell line. After 48 hours, phenanthridinone was detected in the cancer cells but not in the normal cells, indicating that, under the conditions tested, the reaction occurred selectively in the cancer cells.
An important safety concern was whether the system would trigger drug production prematurely in the bloodstream, where carbon monoxide is naturally present. Laboratory testing showed the toxic drug was not produced in blood. The researchers believe this is because carbon monoxide in the bloodstream is largely attached to hemoglobin; in this bound form, the gas appears to be unavailable for the reaction.
“This work represents an important advance in therapeutic in vivo synthetic chemistry,” Tanaka said. “In our therapeutic strategy, molecules naturally present or generated within the body -- including disease-associated metabolites -- are used as endogenous chemical feedstocks to synthesize therapeutic molecules directly at the site of disease.” The team now plans to move beyond cultured cells and test the method in animal models.
Analysis
Why This Matters
- Provides a potential new class of cancer treatment that could dramatically reduce the systemic toxicity and side effects associated with traditional chemotherapy by exploiting a biomarker unique to tumors.
- Represents a significant step forward in the field of therapeutic in vivo synthetic chemistry, using the body's own biological environment to build drugs on demand at the precise location of disease.
- If successful in future animal and human trials, this approach could be adapted to target other diseases that produce distinct chemical signatures.
Background
One of the greatest challenges in cancer treatment is destroying malignant cells without damaging healthy tissue. Traditional chemotherapy drugs can cause serious side effects because they do not selectively target tumors. Carbon monoxide, while best known as a poisonous gas from engines, is also naturally generated by many cancer cells in unusually high amounts. This makes it a potential biological marker for identifying cancer cells, provided it can be safely exploited. Researchers at RIKEN's Biofunctional Synthetic Chemistry Laboratory have been investigating strategies to use such disease-associated metabolites to produce drugs directly inside tumors.
What to Watch
- The outcome of the team's planned experiments in animal models, which will test whether the method works and remains safe in a living organism.
- Whether the albumin-based carrier system can be adapted to deliver other metal catalysts for different chemical reactions against various cancers.
- How the natural variation in carbon monoxide production across different cancer types might affect the treatment's selectivity and effectiveness.
Checked
11 claims in this story checked against 1 source: 11 supported.
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- SupportedRIKEN researchers have developed a method that gets cancer cells to produce drugs that kill them.Latest Science News -- ScienceDaily: “Scientists trick cancer cells into making the drugs that kill them.”
- SupportedThe experimental approach uses carbon monoxide produced by cancer cells to make anticancer compounds inside the cells.Latest Science News -- ScienceDaily: “their experimental approach uses carbon monoxide released by cancer cells to manufacture anticancer compounds directly inside the cells themselves.”
- SupportedThe research was led by Katsunori Tanaka at RIKEN’s Pioneering Research Institute and published in Nature Communications.Latest Science News -- ScienceDaily: “The research, led by Katsunori Tanaka at the RIKEN Pioneering Research Institute (PRI) in Japan, was published in Nature Communications .”
- SupportedThe method could eventually attack tumors while reducing harmful side effects associated with conventional cancer treatments.Latest Science News -- ScienceDaily: “Although the technique is still at an early stage, it could eventually provide a way to attack tumors while reducing the harmful side effects associated with conventional cancer treatments.”
- SupportedThe team used a palladacycle catalyst enclosed in an albumin carrier that shields it from substances such as glutathione.Latest Science News -- ScienceDaily: “The researchers enclosed a palladacycle within albumin, a protein commonly found in blood. This protective protein carrier allows the complex to travel through the bloodstream while shielding the palladium catalyst from substances that would otherwise deactivate it after entering cells.”
- SupportedCarbon monoxide drives a reaction that produces phenanthridinone, whose derivatives can be toxic to cells and are incorporated into anticancer drugs.Latest Science News -- ScienceDaily: “These metal-containing compounds can react with carbon monoxide to produce an organic molecule called phenanthridinone. Certain derivatives of phenanthridinone are toxic to cells and have already been incorporated into anticancer drugs.”
- SupportedThe researchers exposed cultured human liver, cervical, breast and lung cancer cells to the complex for 48 hours and also tested it on a noncancerous cell line.Latest Science News -- ScienceDaily: “they exposed cultured human liver, cervical, breast, and lung cancer cells to the albumin and palladacycle complex for 48 hours. They also tested the compound on a noncancerous cell line”
- SupportedAfter 48 hours, phenanthridinone was detected in cancer cells but not normal cells, indicating selective production under the tested conditions.Latest Science News -- ScienceDaily: “After 48 hours, the researchers detected phenanthridinone in the cancer cell lines but not in the normal cells. The findings indicated that the albumin carrier successfully protected the catalyst from glutathione and that the chemical reaction occurred selectively in the cancer cells under the conditions tested.”
- SupportedLaboratory testing showed that the toxic drug was not produced in blood; the researchers believe this is because carbon monoxide there is largely bound to hemoglobin and appears unavailable for the reaction.Latest Science News -- ScienceDaily: “Fortunately, laboratory testing showed that the toxic drug was not produced in blood. The researchers believe this is because carbon monoxide in the bloodstream is largely attached to hemoglobin”
- SupportedTanaka said, “This work represents an important advance in therapeutic in vivo synthetic chemistry,” and described using molecules in the body as chemical feedstocks to make therapeutic molecules at disease sites.Latest Science News -- ScienceDaily: “"This work represents an important advance in therapeutic in vivo synthetic chemistry," says Tanaka. "In our therapeutic strategy, molecules naturally present or generated within the body -- including disease-associated metabolites -- are used as endogenous chemical feedstocks to synthesize therapeutic molecules directly at the site of disease."”
- SupportedThe researchers plan to test the approach in animal models.Latest Science News -- ScienceDaily: “The researchers now plan to move beyond cultured cells and test the approach in animal models.”
