As the nanoparticles degrade, molecules for imaging and/or therapy form and are retained in the diseased tissue
As the nanoparticles degrade, molecules for imaging and/or therapy form and are retained in the diseased tissue

Smart medicines could generate and then release drugs or molecules that allow imaging of disease when they come into contact with diseased tissues. Key to making them work may be self-assembling nanoparticles.

Researchers in China report their proof-of-concept work in the journal Giant. “We wanted to bridge the gap between small molecule and nanoscale medicines,” says research team member Shiyong Liu at the University of Science and Technology of China.

He explains that traditional small molecule approaches and most types of nanoparticles both suffer from disadvantages. Molecular drugs and imaging agents tend to diffuse quickly from a disease site, even after direct injection, and they can be degraded by the body’s metabolism or quickly excreted. Using nanoparticles to deliver such agents, however, can make it difficult to control the release of active molecules and nanoparticles themselves may not be readily biodegradable.

Liu and his colleagues have combined the targeting power of nanoparticles with automatic generation and release of their active components and biodegradation of the nanoparticles after their job is done.

The nanoparticles self-assemble from polymer molecules into the form of micelles – spherical aggregates incorporating any drugs or imaging agents, or the precursors that will make them, which are added into the mix as the micelles form. They have a chemical structure that causes them to begin to degrade, or ‘self-immolate’ as the researchers describe it, when they encounter specific chemical features found in diseased tissue. The disease-associated triggers for this disruption are an acidic environment and chemicals known as reactive oxygen species.

Liu explains that a key turning point came when the researchers noticed that the staged manner in which the nanoparticles disintegrated was ideal for generating selected small molecules to act as drugs or dyes. The chemical processes occurring as the nanoparticles degrade can actually convert the conjugated molecular cargo into imaging agents or drugs that will be retained within the targeted tissue.

“This was quite unexpected,” says Liu. It makes the nanoparticles ideally suited for ‘theranostics’ – a combination of therapy and diagnostics – overcoming the problems of dispersal and rapid clearance that beset attempts to use small molecules on their own.

The team demonstrated the diagnostic potential of their system by using it for the effective magnetic resonance imaging of tumours in mice. They also expect that incorporating radioactive isotopes into the system could deliver effective and precisely located radiotherapy with extended retention time. By building a library of different nanoparticles by varying the molecular structure of their components the researchers have demonstrated the potential for adapting their system for different applications.

Liu expects that the team will continue to develop wider applications for their nanoparticles, as they also hope to move towards the crucial phase of clinical trials. “Thinking about and exploring the potential is a lot of fun,” he says.

Article details:

Liu, S. et al.: “Self-Immolative nanoparticles for stimuli-triggered activation, covalent trapping and accumulation of in situ generated small molecule theranostic fragments,” Giant (2020)