Scientists develop new concept for hard-to-treat cancers like mesothelioma

Think of a tumor and you might envision a disorganized mass. But tumors can also form a thin sheet over a surface. These can be hard to treat, especially when the surface has wrinkles and crevices. But there may be a new approach. 

Solid tumors can be successfully removed with surgery and residual cells destroyed. But cancers like the asbestos-related lung malignancy mesothelioma grow in thin sheets atop normal tissue. This complex topology makes surgery especially difficult and residual cancer nearly impossible to remove from the body.

A possible new approach for attacking this type of cancer biology was reported recently in the journal Nature Nanotechnology by scientists from the Frederick National Laboratory and collaborators, led by Joel Schneider of the National Cancer Institute.

The scientists engineered a hydrogel that can be sprayed or injected onto large complex surfaces, such as those of the lung or brain. The material spreads out and into crevices and will shape-change to accommodate tissue alterations over time. 

The hydrogel is made of chains of large molecules that will not dissolve in water. It encapsulates nanoparticles designed to penetrate cancer cells and release a payload of genetic material to kill the malignancies, the scientists reported. The nanoparticles incorporate fragments of non-coding RNA, which regulates cellular proliferation and other processes.  

The hydrogels will penetrate normal and cancerous cells and release their payloads. But the RNA will only target cancer cells for destruction because of their abnormal genetic makeup.

The scientists tested the novel material in four mouse models of mesothelioma. In the first experiment, a single injection of the hydrogel successfully reduced tumor growth. In the second scenario, the hydrogel was applied over organs with a complex surface topology and allowed to disseminate for a week. The treatment slowed tumor progression and enhanced survival. 

The third model was designed to mimic an aggressive so-called pleural mesothelioma that attacks the thin membrane covering the chest walls and lungs. A single injection of the hydrogel reduced disease progression and improved survival.

In the final test, the hydrogel was used after cancer surgery to eliminate residual disease. After one month, sites treated with the hydrogel showed faint tumor recurrence, but the untreated areas experienced explosive tumor regrowth.

These proof-of-concept results for mesothelioma suggest a new primary or adjuvant treatment approach for mesothelioma and may lay a foundation to treat other surface-growing cancers such as ovarian and brain tumors, the scientists concluded.

FNL collaborators on the team include Nimit Patel of the Small Animal Imaging Program, Natalia de Val formerly of the Electron Microscopy Laboratory, and Albert Jeon and Baktiar Karim of the Molecular Histopathology Laboratory.