Researchers at USP (University of Sao Paulo) have developed a strategy for treating the most aggressive type of adult brain cancer that combines a photoactive molecule and a chemotherapeutic agent – both encapsulated in nanoparticles.
Research results, supported by Fapesp, were presented at the Fapesp Week France symposium by Antônio Claudio Tedesco of the Center for Nanotechnology and Tissue Engineering and Photoprocesses of the Department of Chemistry of the FFCLRP-USP (Faculty of Philosophy, Sciences and Letters of Ribeirão Preto).
Grade four glioblastoma multiforme represents almost 25% of nonmetastatic brain tumors. The new therapy may be used before, during and after tumor removal surgery, which is mandatory in these aggressive cases. The use of nanoparticles, according to the researcher, allows the active compounds to be released directly into the affected region gradually and sustainably for a few months.
"The less brain tissue is removed, the safer the surgery, as the risk of compromising the patient's vital functions considerably decreases," said Tedesco.
Data from experiments done on tumor cell cultures were published in a study in the journal Molecular Pharmaceutics.
The group soon intends to evaluate the effect of treatment on animals before, during and after surgical removal of the tumor. The proposal is to enrich the affected region with photoactive molecules about two weeks before surgery. During this period, simultaneously, the chemotherapist will be acting to reduce the tumor mass.
During surgery, light will be applied to activate the photosensitive compounds. "At this point, with the removal of the skullcap and tumor, it is possible to protect the healthy tissue with phototherapy and kill the diseased cells that may remain impregnated in the tissue," said the researcher.
In the postoperative period, the new treatment may help prevent relapse, since nanoparticles are able to gradually release chemotherapy directly into the tumor region, without causing side problems to the debilitated patient.
"It is precisely during this period that 90% of patients relapse and usually very aggressively. However, as they are weakened, it is not possible to submit them to radiotherapy or conventional chemotherapy. With the new method, we can continue the fight disease for a month after surgery, "said Tedesco.
Conventional chemotherapy treatment against glioblastoma involves the administration of the high-cost temozolomide drug with little guarantee of efficacy. Adverse effects of the dose required to cross the blood-brain barrier – which protects the central nervous system – include damage to the bone marrow, where the hematopoietic stem cells are responsible for generating blood and immune cells.
Tedesco points out that nanotechnology and new drug delivery systems with lipid-protein nanoparticles have allowed molecules previously used to treat certain conditions to be "redesigned" and adapted to new functions.
Thus, the same system used for the treatment of glioblastoma can act in the diagnosis of the disease and provide important information for tumor removal surgery by means of a fluorescent marker.
Currently, before surgery, tomography or resonance images capable of detecting tumor mass are used. "The neurologist decides the safety margin that should be removed. With the new system, it is possible to know exactly what is the mass to be removed," he said.
The same carrier systems containing the actives described above may further be used for the marking and diagnosis of less severe types of glioblastoma. "We would like to take the same approach to identify patients with grade two and three tumors who are not yet indicated for surgical intervention. That way we can treat the disease before it progresses," said Tedesco.
"If we have to move on to surgery, our idea is that with the 3D organ printing technology, already available at the Nanotechnology Center, we can build a prosthesis with the exact size of the tumor to be removed. We can impregnate this material with chemotherapy and implant it in the patient to sustainly release the active compound for weeks or months, "he said.
Tedesco's group is one of the pioneers in Brazil in the area of dynamic phototherapy. Work in this field began with the treatment of skin cancer and rapidly advanced to tissue engineering and regenerative organ and tissue medicine. Among the studies already done are an artificial model of human skin – today produced for the treatment of burns and healing.
There are also works with highly specific drug carrier systems that can be used to treat neurodegenerative diseases such as Parkinson's, Alzheimer's and epilepsy.
The Fapesp Week France symposium was held from 21 to 27 November thanks to a partnership between Fapesp and the universities of Lyon and Paris, both of France.