Exosomes in our bodies function much like your neighbourhood couriers. Just as couriers transport packages containing important information or goods from one location to another, exosomes carry various cargo molecules, including proteins, messenger RNAs and microRNAs, facilitating communication between cells. These tiny spheres transport fats, proteins and genetic material, playing a crucial role in regulating everything from pregnancy and immune responses to heart health and kidney function. A recent study published by Columbia University suggests that these nanobubbles could be utilised in inhalation therapy to treat lung cancer.
Lung cancer is widespread and has one of the lowest survival rates among cancers. Cytokines, such as interleukin-12 (IL-12), show promising potential as potent tumour suppressors. However, their effectiveness is limited by severe adverse effects.
Now, a groundbreaking method developed by Ke Cheng, a biomedical engineering professor, and his research group presents a new avenue. Exosomes, naturally secreted by the body or cultured cells, possess low toxicity and multiple mechanisms for delivering their cargo into cells.
Historically, clinicians have primarily administered IL-12 for cancer treatment through direct injection into tumours or the bloodstream. While scientists have previously used liposomes or lipid nanoparticles to deliver mRNA, these methods face challenges such as insufficient tissue targeting and concerns about long-term toxicity. Over the past 15 years, Cheng’s group focused on developing exosomes as superior drug delivery carriers compared to liposomes and lipid nanoparticles, particularly in specific medical applications.
Cheng's laboratory discovered that administering IL-12 mRNA enclosed in exosomes via inhalation not only localises concentrated IL-12 delivery to the lungs but also enhances cancer-fighting efficacy with minimal side effects. Moreover, inhalation is entirely noninvasive; there is no requirement for a nurse to administer treatment intravenously. It was observed that the inhalation method is more efficient in building higher concentrations of IL-12 right where it is needed than other ways of delivering mRNA.
Inhaling the nanobubbles containing the blueprint for IL-12 can activate lung immune cells and transform them into formidable defenders capable of releasing substances that directly target and eliminate tumour cells. Furthermore, IL-12 aids in training these immune cells to remember the unique characteristics of tumour cells. Consequently, if the tumour attempts a resurgence, these well-prepared immune cells promptly recognise and eradicate it.
Additionally, these empowered immune cells can transmit their acquired knowledge to untrained immune cells throughout the body, forming a defensive army. This implies that even if tumour cells attempt to spread beyond their original site, these primed immune cells can detect and eradicate them, establishing a comprehensive body-wide defence against cancer. Cheng expects a human trial to launch in five years.