Researchers have successfully repurposed nano-sized particles released by cells, such as red blood cells, to function as drug delivery platforms carrying antisense oligonucleotide (ASO) molecules targeting lung cancer cells. This innovative approach, detailed in eBioMedicine, shows promise in suppressing cancer progression, particularly in cases resistant to traditional therapies. The study was a collaborative effort involving the National University of Singapore (NUS) and the Agency for Science, Technology and Research (A*STAR).
Overcoming Drug Resistance in NSCLC
Non-Small Cell Lung Cancer (NSCLC), especially in non-smokers, is a leading cause of cancer mortality. A significant challenge in treating NSCLC is the rapid development of drug resistance. Mutant Epidermal Growth Factor Receptors (EGFRs) are a common driver of lung cancer, particularly among Asian populations. Current treatments, such as tyrosine kinase inhibitors (TKIs), face the issue of cancer cells mutating and resisting these drugs. To address this, researchers have turned to ASOs, which can be redesigned to target and fix problems in different genes, offering a flexible tool to combat resistance.
Targeted Delivery with Red Blood Cell-Derived EVs
To overcome the limitations of ASOs, such as their degradation in the bloodstream, the researchers utilized extracellular vesicles (EVs) derived from human red blood cells as natural carriers. These EVs were engineered with EGFR-targeting moieties on their surface, enabling them to home in on cancerous cells. The ASO-loaded EVs demonstrated a potent anti-cancer effect in various lung cancer models, including patient-derived cells. The ASOs were specifically designed to suppress mutant EGFR while leaving normal EGFR unaffected.
Precision Medicine Approach
"The innovative use of extracellular vesicles as a delivery vehicle for nucleic acid therapeutics added a potentially powerful treatment modality for treating malignancies," said Associate Professor Tam Wai Leong, Deputy Executive Director of ASTAR Genome Institute of Singapore (ASTAR GIS), and co-corresponding author of the study. "The ability to precisely eliminate mutant EGFR cancer cells while sparing normal tissues will enable customised treatment for individual patients. This is a significant step towards addressing cancer drug resistance and advancing the application of personalised cancer medicine."
Professor Goh Boon Cher, Deputy Director of the NUS CSI, added, "This work is instrumental in breaking new ground for precise delivery of therapeutic RNA to tumour cells to destroy them by targeting their vulnerabilities. It is a proof of concept that can be broadly applied in other areas of cancer treatment."
