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

Synthesis and active assembly of DNA networks by biomolecular nanomachines

 

Cells use molecular nanomachines, such as enzymes and motor proteins, to perform work and actively control the organization of matter within them. In this context, microtubules—filamentous structures made of tubulin proteins, which are part of the cellular cytoskeleton—serve as tracks for the transport and organization of components within cells. Motor proteins, such as kinesins and dyneins, move along microtubules, transporting molecules in different directions: kinesins move cargo from the center of the cell toward the membrane, whereas dyneins move it in the opposite direction. These proteins use the chemical energy of ATP to power their movement.

These ATP-dependent processes are known as active assembly, and they allow the generation of structures and complex transformations that do not occur through conventional self-assembly. Understanding and reproducing active assembly represents an important challenge for nanoscience, as it could enable the fabrication of materials with high levels of organization and dynamic responses.

A team of researchers in Japan developed a strategy for fabricating molecular materials using one of these biomolecular nanomachines. They attached DNA strands to microtubules and increased the length of the strands using the enzyme DNA polymerase, which is responsible for replicating genetic material. They then placed the microtubules in a chamber on whose surface they anchored kinesins.

Using fluorescence microscopy, they observed that adding an ATP-containing solution induced the microtubules to move, causing the long DNA strands attached to them to stretch and intertwine, forming a two-dimensional network within a few minutes. Finally, they determined that the concentration of microtubules and the duration of the DNA synthesis altered the connectivity and complexity of the two-dimensional network.

The DNA–microtubule system provides a model for studying how forces generated by molecular motors can control the formation, connectivity, and organization of networks. Moreover, DNA sequences can be designed to program the interactions and connectivity of the network. This work proposes a strategy for fabricating biomaterials using active molecular nanomachines, paving the way for the development of bioinspired materials with adaptive and potentially self-healing properties.

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