NTU Singapore’s Microscopic Peptide Droplets Slash Colorectal Tumour Growth by 67%

A New Approach to an Old Problem

Colorectal cancer remains one of the most challenging malignancies to treat, particularly when tumours develop resistance to immune checkpoint inhibitors. Current therapies rely on monoclonal antibodies to block the interaction between PD-1 on T cells and PD-L1 on tumour cells—a “false handshake” that allows cancer to evade immune attack. While effective for some patients, these antibody treatments are expensive to produce and can be limited by systemic toxicity.

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have taken a fundamentally different approach. Rather than blocking the interaction from outside the cells, they developed microscopic peptide droplets that deliver small interfering RNA (siRNA) to silence the production of PD-1 and PD-L1 at their source. The result, published in Biomaterials, was a 67% reduction in tumour growth in preclinical models—a level comparable to the combination of anti-PD-1 and anti-PD-L1 antibody treatments used as a benchmark.

How the Dual-Droplet System Works

The system uses two separate peptide microdroplet formulations administered together. One, known as siPD-1@THC, carries siRNA against PD-1 and is fitted with anti-CD3 antibodies to target T cells. The second, siPD-L1@HC, delivers siRNA against PD-L1 into colorectal cancer cells. Once inside, the siRNA molecules destroy the genetic instructions needed to produce these checkpoint proteins, effectively disarming the tumour’s immune evasion mechanism from within.

“Our approach works from inside both types of cells,” explained Professor Ali Miserez, senior author of the study. “The siRNA destroys the instructions they need to make these proteins. It is a little like throwing a spanner into a production line, except the disruption is targeted at the recipe for PD-1 or PD-L1”.

Cost Implications and Future Potential

Perhaps the most significant aspect of this research is its economic potential. The researchers estimate that an siRNA-based approach could cost five to ten times less to produce than monoclonal antibody treatments if successfully scaled up. Given the growing burden of cancer care on healthcare systems worldwide, this cost advantage could make immunotherapy accessible to a far broader patient population, particularly in low- and middle-income countries where colorectal cancer incidence is rising.