From the intricate scaffolds of coral reefs to the sturdy architecture of bones, Nature has long mastered the art of building with a blend of the mineral and the organic. Now, scientists are drawing inspiration from Nature’s methods not just to build, but to break down. Their targets? Cancer cells.
The key is biomineralisation, a process where organisms selectively deposit mineral ions within soft tissues and cells to harden functional structures, much like how steel bars reinforce concrete. By mimicking this process, researchers like Zibiao Li are developing precursor materials that can infiltrate cancer cells, inducing mineralisation in disruptive places to ultimately destroy them from within—all while preserving healthy tissue.
“Besides their potential specificity, biomineralisation materials—such as calcium phosphate, silica, and gold nanoparticles (GNPs)—are highly biocompatible and degrade naturally within the body, reducing their long-term side effects,” said Li, Division Director at the A*STAR Institute of Sustainability for Chemicals, Energy and Environment (A*STAR ISCE2) and a Senior Principal Scientist at the A*STAR Institute of Materials Research and Engineering (A*STAR IMRE).
However, current biomineralisation-based strategies can be inefficient. Li noted that they often require large doses of mineral ions over extended periods, limiting their safe clinical use. Seeking more optimised options, Li and A*STAR ISCE2 colleagues teamed up with Yun-long Wu’s team at Xiamen University’s School of Pharmaceutical Sciences, China, to design a novel tool: a mitochondria-targeted polymer-gold molecular complex dubbed TPPM-Au.
Mitochondria are specialised structures within cells that serve as both power plants and gatekeepers of apoptosis, the self-destruct mechanism that normally disposes of old or damaged cells.
“In cancer cells, mitochondria have membrane features that set them apart from healthy cells, making them more vulnerable to targeted therapies,” said Li. “Cancer cells also rely on mitochondria more than healthy cells do; not only for metabolism, but for therapy resistance.”
In designing TPPM-Au, the team included gold ions for another advantage: once inside cells, these ions transform into GNPs. When exposed to specific wavelengths, GNPs convert light to heat, burning solid tumours in a process called photothermal therapy. At the same time, GNPs generate ultrasound waves, enabling real-time treatment monitoring with photoacoustic imaging tools.
When the team tested TPPM-Au in different cell lines, they found the mitochondria-targeting portion, TPP, guided the complex to deliver gold ions selectively into cancer cells over healthy ones. Inside their target cells, GNPs formed and depleted stores of glutathione, a key antioxidant. Left vulnerable, the cancer cells succumbed to mounting oxidative stress, which triggered apoptosis at double the rate of healthy cells (45.5 versus 25.3 percent).
The team also observed that pairing TPPM-Au with near infra-red irradiation for photothermal therapy intensified cancer cell destruction in both lab-grown cells and mouse models while the inhibition of solid tumours was improved by about 10 times compared to the control group.
Li noted that their work lays a foundation for more precise and efficient biomineralisation-based cancer treatments, adding, “To follow up, our team will explore TPPM-Au’s long-term effects on tumour progression and health, while evaluating possible combinations with other cancer therapies for better results.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Institute of Sustainability for Chemicals, Energy and Environment (A*STAR ISCE2).
