How to Turn a Virus into an Anti-Cancer Nanobioparticle

Even viruses can become our allies. Certain viruses, particularly those that infect bacteria, can be genetically modified to serve as targeted nanobioparticles capable of destroying specific cancer cells and tissues. A research team from the University of Bologna has modified bacteriophages into nanoparticles for this purpose. The study was conducted as part of the NanoPhage project, financed by the AIRC Foundation for Cancer Research. Published in the journal Small, the results demonstrated the potential of this approach to serve as an important tool in diagnostics and therapeutics, including oncology.

Matteo Calvaresi, Professor at the Department of Chemistry of the University of Bologna, researcher at the Sant’Orsola-Malpighi Polyclinic and coordinator of the study, explained: "We developed and tested a method that exploits the properties of specific viruses that are harmless to humans. When modified in the lab, these viruses, could help overcome several limitations in the use of nanoparticles in medicine. For instance, the nanobioparticle we created can rapidly and selectively destroy cancer cells and tissues when exposed to light, sparing healthy cells".

Nanomedicine, the clinical application of nanotechnology, has long been discussed and considered a promising field. One of the advantages of using nanoscale particles is their potential to significantly amplify and concentrate the therapeutic effects of a single molecule, such as a drug, while drastically reducing the dosage required and, consequently, minimising potential side effects.

However, progress in the field has been hindered by a major challenge: the current inability to synthesise homogeneous nanostructures.

Professor Calvaresi added: “In macroscopic production, uniformity is achieved using moulds. This approach is not possible for nanoparticles, because we’re dealing with objects on the scale of billionths of a metre, and moulds that small do not exist.” As a result, even with the most precise synthesis methods, scientists end up producing billions of nanoparticles with slightly different shapes and sizes. That said, it is possible to construct perfectly reproducible nanoscale particles, as this often happens in nature. Viruses, for example, are nanoscale objects whose assembly, shape, and size are strictly determined by their genetic material. This observation inspired the scientists to develop a system to synthesise nanoparticles with therapeutic potential by using a virus as a base.

Professor Calvaresi explained: “We started with the M13 bacteriophage, a virus that infects bacteria but is harmless to plants, animals and humans, and used it as a template for synthesising nanoparticles. To achieve this, we ‘decorated’ the protein shell, or capsid, with photoactive molecules that release toxic species when exposed to light”.

By doing so, the researchers transformed the viruses into nanobioparticles, all identical in structure, that can be used in medicine, for example, to selectively destroy cancer cells and tissues. The nanobioparticles were successfully tested on both cultured cells and lab animals.

Professor Calvaresi concluded: “The new nanobiostructure can selectively target cancer cells and penetrate the complex three-dimensional architecture of tumours, thus overcoming one of the major limitations of current anti-cancer therapies. This is achieved thanks to the spaghetti-like

structure of the bacteriophage and the genetic engineering of its extremities with molecular ‘keys’ that recognise ‘locks’ unique to cancer cells”. Further research is needed to assess whether these findings can be applied to patients.

The results were published in the journal Small under the title “Phage-Templated Synthesis of Targeted Photoactive 1D-Thiophene Nanoparticles”. The study was coordinated by Professor Matteo Calvaresi, in collaboration with research teams led by Professor Alberto Danielli (Department of Pharmacy and Biotechnology, University of Bologna), Dr. Francesca di Maria (ISOF-CNR, Bologna), and Dr. Claudia Tortiglione (ISASI-CNR, Pozzuoli). The research was made possible through the NanoPhage project, supported by the AIRC Foundation for Cancer Research, and carried out at the NanoBio Interface Lab of the University of Bologna.