Programmable In Vivo Synthesis of Quantum Dots for Cancer Treatment

 

Quantum dots (QDs) are semiconductor nanoparticles capable of converting incident light into heat or re-emitting it at different wavelengths. In medicine, silver selenide QDs are promising because they are sensitive to near-infrared light (NIR-II), which can penetrate biological tissues with relative ease. However, when these nanoparticles are synthesized in vitro and injected into the body, they are rapidly cleared by the organism before reaching the tumor.

To overcome this obstacle, a team from Nankai University in China developed an innovative strategy: synthesizing quantum dots directly inside cancer cells.

To achieve this, the researchers developed a multifunctional platform known as a spatially hierarchical integrated nanosynthesizer, or SHINE, which delivers the two ingredients needed to form Ag₂Se quantum dots: silver and selenium.

SHINE integrates a ferritin-encapsulated silver source with a selenium source specifically synthesized for this purpose. Both are contained within a physically isolated, silica-coated nanocapsule that is sensitive to glutathione. The key to the system lies in its sequential release mechanism: the silica layer acts as a timer, regulating the precise moment at which the two precursors are released.

The mechanism is activated by the tumor itself. Cancer cells have a microenvironment rich in glutathione, an endogenous antioxidant. Glutathione degrades the SHINE coating, releasing selenium first and silver afterward. Within the malignant tissue, the two components spontaneously react to form nanocrystals as small as 3 nm.

In experiments using mouse models, fluorescence produced by laser excitation illuminated the tumors two hours after injection and remained stable for several days. In addition to serving as imaging agents for diagnostic purposes, the process provides an additional therapeutic function. The formation of the Ag₂Se particles depletes glutathione in the tumor, weakening its antioxidant defenses and increasing oxidative stress. When exposed to NIR-II infrared light, the quantum dots reach temperatures of 50–56 °C, destroying cancer cells through photothermal therapy. Tumor growth is reduced by more than 50%, while laser irradiation increases tumor inhibition to as much as 70%.

This advance demonstrates a strategy for the controlled production of functional nanomaterials within living organisms and opens the possibility of synthesizing diagnostic and therapeutic agents in situ, potentially avoiding the toxicity associated with administering prefabricated nanoparticles.

Angewandte Chemie International Edition