## A New Delivery System for Chemotherapy Shows Promise in Targeting Leukemia
For decades, 5-fluorouracil (5FU) has been a cornerstone in teh fight against cancer. Its effectiveness stems from its ability too disrupt DNA replication in rapidly dividing cancer cells, ultimately leading to their demise. Though, the benefits of 5FU are frequently enough overshadowed by meaningful and debilitating side effects, including nausea, extreme fatigue, and even heart failure.
The root of the problem isn’t necessarily the drug itself, but its limited solubility in the bloodstream. This poor solubility causes the drug to aggregate, hindering its ability to reach cancerous cells and leading to indiscriminate damage to healthy tissues along the way. As chemist and nanoscience expert Chad mirkin of Northwestern University succinctly puts it, conventional chemotherapy is both toxic *and* poorly absorbed by the body.
Mirkin’s team has taken a novel approach to address these challenges, focusing not on altering the 5FU molecule, but on redesigning how it’s delivered. They’ve successfully integrated 5FU into strands of synthetic DNA, which are then wrapped around microscopic spheres, creating structures called spherical nucleic acids (SNAs).
This innovative design leverages the body’s own cellular mechanisms.Cells possess ”scavenger receptors” on their surfaces, designed to recognize and internalize specific molecules. Notably, myeloid cells – those that become cancerous in acute myeloid leukemia – exhibit a significantly increased expression of these receptors. This essentially creates an invitation for the SNAs to enter the cells,unknowingly delivering a lethal payload.
Once inside,naturally occurring intracellular enzymes break down the DNA shell,releasing the 5FU directly within the cancer cell. This allows the drug to act with heightened efficiency, targeting the cancer from within.
Early results from animal models of acute myelogenous leukemia are remarkably encouraging. The SNA-encapsulated 5FU demonstrated a 12.5-fold increase in penetration into leukemia cells compared to the standard formulation.Furthermore,its destructive power was amplified by up to 20,000 times,and tumor progression was reduced by a factor of 59. Crucially, no detectable side effects were observed in the treated animals.
Mirkin expresses considerable optimism, noting that tumor progression halted fully in the tested models. Leukemia cells were virtually eliminated from the blood and spleen, while healthy tissues remained unharmed. This targeted approach represents a fundamental shift from the current paradigm of systemic toxicity. Instead of broadly poisoning the body, this nanomedicine delivers a concentrated dose precisely were it’s needed.
Published in *ACS Nano* (https://doi.org/10.1021/acsnano.5c16609), these findings suggest a broader therapeutic potential. Seven SNA-based therapies are already undergoing clinical trials, and mirkin’s team is actively exploring applications for a range of other conditions, including various cancers, infectious diseases, neurodegenerative disorders, and autoimmune diseases.
The next phase involves expanding these experiments to larger animal cohorts and more complex models, paving the way for eventual human clinical trials. While a lengthy process still lies ahead, this research offers a promising path towards a future of chemotherapy that effectively treats disease without causing widespread destruction.
