UNIVERSITY OF SÃO PAULO - BRAZIL

Scientists from Brazil and India Study Possible Treatment for Solid Tumors

In animal tests, nanoparticles containing substances already approved for human use reduced inflammation in the biological microenvironment where such cancers develop, facilitating the action of the immune system.

April 25, 2024 – Published 1 month ago

Text: Ricardo Muniz
Art: Diego Facundini

A recently published article in the Journal of Controlled Release details the results of an international scientific collaboration that developed an alternative treatment for solid tumors by inhibiting the so-called inflammatory tumor microenvironment (TME).

Solid tumors are among the most challenging types of cancer to treat due to the difficulty of drug penetration. The inflammatory tumor microenvironment, where the tumors are located, contains various cells and substances from the patient that prevent the immune cells from combating the tumor. “Often these cells and molecules help the tumor grow, and that’s why we say it escapes the immune system’s surveillance,” explains Lúcia Helena Faccioli, a full professor at the School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP) at USP and coordinator of the Lipid Quantification and Identification Center (Ceqil), established with support from Fapesp through the Multi-User Equipment Program.

Lucia Helena Faccioli – Photo: Marcos Santos/USP Images.

“There is always a tug-of-war between tumor-promoting and tumor-inhibiting immune cells in the TME, where metabolites, lipid mediators, cytokines, and chemokines play an important role in dominating the immunosuppressive nature,” write the authors of the article, which include researcher Viviani Nardini from the Department of Clinical, Toxicological, and Bromatological Analysis at FCFRP-USP and scientists from Indian institutions led by Avinash Bajaj, head of the Nanotechnology and Biological Chemistry Laboratory at the Regional Centre for Biotechnology in Faridabad, Haryana, India.

The team developed nanomicelles—very small particles, measuring between 1 and 100 nanometers—composed of different substances, hence called chimeras. The chimeric nanomicelles produced are composed of phospholipids (NMs), docetaxel (DTX), a substance used to kill tumor cells, and dexamethasone (DEX), an anti-inflammatory widely used to reduce the production of various inflammatory substances, such as prostaglandin E2 (PGE2).

Laboratory animal studies showed that these particles (NMs+DTX+DEX), administered intravenously, were very efficient, reducing tumor size and increasing the animals’ survival: untreated animals always die around 28-30 days, but treated animals survive up to 44-50 days, explains Faccioli.

The chimeric nanomicelles are composed of phospholipids (NMs), docetaxel (DTX), a substance used to kill tumor cells, and the anti-inflammatory dexamethasone (DEX) – Photo: researchers’ archive.

“The treatment induced more than a fivefold decrease in tumor volume compared to untreated tumors in the colon cancer model,” details Bajaj. The nanomicelles reduced and altered the cells present around the tumor, those that impede the immune system’s action, promoted the increase of specific types of leukocytes that kill tumor cells, and also inhibited the release of PGE2, an inflammatory substance present in the tumor microenvironment that reduces the antitumor action of certain defense cells.

“Although these studies were conducted in animals, the results are very promising and open up possibilities for human studies, as the particles are composed of compounds already approved for human use,” celebrates Faccioli, who completed her postdoctoral studies at the National Heart and Lung Institute at the University of London.

In addition to USP and the laboratory coordinated by Avinash Bajaj, the research involves the Amity Institute of Integrative Sciences and Health (Haryana), the Department of Surgical Oncology at the All India Institute of Medical Sciences (New Delhi), the National Institute of Immunology (New Delhi), and the National Institute of Biomedical Genomics (Kalyani, West Bengal).

The article “Engineered nanomicelles inhibit the tumor progression via abrogating the prostaglandin-mediated immunosuppression” can be read at: www.sciencedirect.com/science/article/pii/S0168365924001615.

From Agência Fapesp
Intern under the supervision of Moisés Dorado