Unlocking the Power of Inhaled Therapy for Lung Cancer

Columbia Biomedical Engineer Ke Cheng has developed a method that makes use of inhalation of exosomes, or nanobubbles, to immediately ship IL-12 mRNA to the lungs of mice.

Lung most cancers is one of the commonest cancers and has one of the lowest survival charges in the world. Cytokines, that are small signaling proteins, akin to interleukin-12 (IL-12), have demonstrated appreciable potential as sturdy tumor suppressors. However, their functions are restricted as a result of a large number of extreme unwanted side effects.

In a paper printed just lately in Nature Nanotechnology, Biomedical Engineering Professor Ke Cheng and his analysis group show that utilizing nanobubbles, known as exosomes, via an inhalation therapy technique can immediately ship IL-12 messenger RNA (mRNA) to the lungs. mRNAs are the blueprints for producing particular proteins that take part in a range of mobile features.

While scientists have beforehand used liposomes (tiny fat-based particles) or lipid nanoparticles (LNPs) to ship mRNA, this technique has a number of issues, together with a scarcity of tissue homing, the place the particles don’t go to the goal organs, and issues about the potential toxicity after long-term publicity. Over the previous 15 years, Cheng’s group has been growing exosomes for use as superior drug supply carriers over liposomes and LNPs in particular indications.

Innovative Delivery Through Inhalation

Up to now, clinicians have solely been ready to make use of IL-12 to deal with most cancers by injecting it immediately into the tumor or into the bloodstream. Cheng’s lab discovered that having the affected person — on this case, mice — inhale IL-12 mRNA in exosomes couldn’t solely ship domestically concentrated IL-12 into the lungs but in addition might higher struggle the most cancers with minimal unwanted side effects. The inhalation technique is extra environment friendly in building greater concentrations of IL-12 proper the place it’s wanted than different methods of delivering mRNA akin to utilizing liposomes.

“Exosomes are usually injected systemically into the bloodstream,” stated Cheng. “In this new study, we show that inhaled exosomes can efficiently reach the lung and deliver an anti-lung cancer cargo, IL-12 mRNA. This is a major step forward in advancing the development of new inhalable drugs to treat lung cancer, which has one of the lowest five-year survival rates in the world.”

Immune System Activation and Tumor Resistance

Inhaling the nanobubbles with the IL-12 blueprint can kickstart the lung immune cells, turning them into highly effective defenders outfitted to launch substances that immediately goal and destroy tumor cells. In addition, IL-12 helps train these immune cells to “remember” the distinctive options of tumor cells. As a consequence, if the tumor tries to assault once more, these well-informed immune cells are prepared to acknowledge and eradicate the tumor swiftly.

Additionally, these supercharged immune cells can unfold their newfound information to different, untrained immune cells all through the body, creating a military of defenders. This implies that even when tumor cells attempt to unfold past their unique location, like the lungs, these ready immune cells can spot and wipe them out, providing a body-wide protection system in opposition to most cancers. The mice that inhaled this remedy demonstrated lung tumor suppression in addition to heightened resistance in opposition to tumor rechallenges.

Combining Efficacy With Simplicity

This technique stands out as a potent IL-12 mRNA supply system to the lung microenvironment, say the researchers, and combines simplicity with efficacy in opposition to major tumors and metastases. Compared to different nanoparticle controls, exosomes enhance IL-12 expression with mitigated toxicity. And sufferers are prone to be a lot happier with merely inhaling the therapeutic reasonably than receiving intratumoral injections.

Future Directions

Cheng’s group is now working with Columbia University Irving Medical Center oncologists to translate their outcomes into the clinic to profit lung most cancers sufferers.

Reference: “Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity” by Mengrui Liu, Shiqi Hu, Na Yan, Kristen D. Popowski and Ke Cheng, 11 January 2024, Nature Nanotechnology.
DOI: 10.1038/s41565-023-01580-3