Foto del docente

Suleman Khan Zadran


Dipartimento di Farmacia e Biotecnologie

Settore scientifico disciplinare: BIO/11 BIOLOGIA MOLECOLARE


There are also good viruses: developed a photoactive viral vector for anticancer therapy

An anti-cancer phage developed by a research group of the University of Bologna. It is a harmless virus to humans, genetically engineered and chemically modified to selectively kill cancer cells only. The targeted and non-invasive treatment is activated by light.

Not all viruses come to harm. A research group from the University of Bologna has developed a new targeted cancer therapy based on the action of a genetically modified phage - a virus that infects bacteria.

The study - which captured the cover of Nanoscale magazine - was carried out as part of the NanoPhage project, supported by the AIRC Foundation for Cancer Research. The results show how it is possible to engineer a particular type of virus, phage M13, so that it can selectively eliminate only cancer cells. For this purpose, the virus has been modified in such a way that it has the ability to transport a drug that can be activated through light to cancer cells to target.

“Today more than ever we know that viruses can be dangerous adversaries for humans. However, it is important to remember that some viruses can prove to be valuable allies in the fight against diseases, including cancer ”, explains Matteo Calvaresi, professor at the Giacomo Ciamician Department of Chemistry at the University of Bologna and coordinator of the study.

Bacteriophages, or simply phages, are widespread viruses that affect bacteria but are harmless to plants, animals and humans. Due to this characteristic, and their particular structure, they can be genetically modified and thus transformed into vectors capable of delivering drugs in a targeted manner within an organism.

Scholars have experimented with this opportunity with phage M13, a filamentous virus 1000 nanometers long but just 5 nanometers wide (one nanometer equals one billionth of a meter). Due to its characteristics, this virus can become an effective platform for hosting and transporting nanomaterials. In particular, the goal was to transform the virus into a tool to implement anti-cancer photodynamic therapy: a targeted and non-invasive treatment, which can be activated with light pulses.

"We used this phage to transform it into a vehicle capable of directing hundreds of molecules onto the surface of cancer cells, which then penetrate inside through a process, called endocytosis, mediated by receptors", says Luca Ulfo, PhD student of the University of Bologna and co-first author of the study.

The researchers genetically engineered the phage to selectively target a specific receptor , called EGFR, which is expressed in excess in several types of cancers, including those in the breast, lung, brain and colon. This way the virus only reaches the cancer cells. In addition, some molecules have been chemically attached to the protein envelope surrounding the genome of the virus that allow the activation of photodynamic therapy.

“These molecules are compounds, called photosensitizers, which can be activated by a light stimulus. Furthermore, they are able to transform the oxygen normally present in our body into a highly reactive chemical agent, capable of killing cancer cells ”, adds Andrea Cantelli, researcher at the University of Bologna and co-first author of the study.

The ability of the modified virus to specifically recognize cancer cells and the ability to precisely control the area in which to activate the therapy, irradiating it with light, are characteristics that could help drastically reduce the side effects of anticancer therapies. The results obtained are the first important step towards a clinical trial of this viral vector, which could also find further medical applications.

"The peculiarity of this new instrument lies in the great flexibility offered by phage biology, which allows the development of innovative approaches in the field of theranostics, biosensors and precision medicine", explains Alberto Danielli, professor at the Department of Pharmacy and Biotechnology of the University of Bologna, one of the study coordinators. "In addition to the specific application we have made, the virus could be modified in other ways, to reach cells of different types, and even to fight pathogenic bacteria that have developed resistance to antibiotics."

The results were published in the Nanoscale journalin the article entitled “Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy”. The study was carried out by a research group that involved three departments of the University of Bologna: Luca Ulfo, Annapaola Petrosino, Paolo Emidio Costantini, Michela Nigro, Francesco Starinieri, Suleman Khan Zadran, Giampaolo Zuccheri and Alberto Danielli (Department of Pharmacy and Biotechnology); Andrea Cantelli, Roberto Saporetti, Matteo Di Giosia and Matteo Calvaresi (Department of Chemistry “Giacomo Ciamician”); Eleonora Turrini (Department of Sciences for the Quality of Life). The research was made possible thanks to the NanoPhage project, supported by the AIRC Foundation for Cancer Research and active at the NanoBio Interface Lab.

Pubblicato il: 01 novembre 2022