A downside to liposome drug delivery?
Precisely targeting a drug to the right part of the body is always hard, but drug delivery is at its most challenging when the therapeutic is genetic material.
Unlike other classes of biologic drugs, DNA and RNA are not stable in circulation, so scientists have used lipid capsules called liposomes to envelop the therapeutic genes and shuttle them safely to the appropriate destination.
The human body treats engineered liposomes — and all drugs — like foreign objects. Upon injection, the immune system reacts to the circulating lipid capsules, and the white blood cells known as macrophages begin engulfing and clearing the perceived intruders.

For many years, this phenomenon was not a problem, according to Yue Li, a researcher at Xuzhou Medical University in Jiangsu, China.
“In recent decades, countless nanoparticles have been designed for drug delivery, and there are over 20 liposomal products available on the market,” Li said.
These medicines have been shown to be safe and effective by regulatory agencies such as the United States Food and Drug Administration.
However, in a study published in the Journal of Lipid Research, Li, along with co–first author Ran Yao and colleagues, showed that liposomes can have a negative impact on bone marrow macrophages.
These scientists knew that as macrophages encounter and engulf liposomes, they begin to accumulate lipid droplets. Researchers had put this to clever use delivering fluorescent labels into immune cells during lab experiments, but Li realized that the same phenomenon might be occurring when liposomes are administered as drugs. Indeed, previous work had shown it occurs in the liver.
To test the theory, Li and a team of researchers at the Xuzhou Medical University injected mice with liposomes and then collected macrophages from the mouse bone marrow for study. The result is stunning: Macrophages in the bone marrow underwent pro-inflammatory activation and showed signs of stress, such as lipid accumulation in the endoplasmic reticulum. This led to a decreased ability to create red blood cells and important immune cell types like monocytes.
What does this mean? Li said he thinks the finding “provides a novel consideration criteria for clinical drug trials.” That is, patients who are immunocompromised or who have bone marrow infections might need to avoid liposome drug trials.
While this may be true, the finding must be replicated in human macrophages and tissue samples before researchers can be sure. The work also should be extended beyond liposomes to other classes of lipid nanoparticles.
It’s not all bad news for liposomal drugs, either. For years, researchers have worked to engineer the surface of nanoparticles to escape immune detection. The original motivation was to increase effectiveness by keeping the drug in circulation longer. Now, those modifications may have a secondary benefit: sparing the hardworking bone marrow macrophages.

Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles

Training AI to uncover novel antimicrobials
Antibiotic resistance kills millions, but César de la Fuente’s lab is fighting back. By pairing AI with human insight, researchers are uncovering hidden antimicrobial peptides across the tree of life with a 93% success rate against deadly pathogens.

AI-designed biomarker improves malaria diagnostics
Researchers from the University of Melbourne engineered Plasmodium vivax diagnostic protein with enhanced yield and stability while preserving antibody-binding, paving the way for more reliable malaria testing.

Matrix metalloproteinase inhibitor reduces cancer invasion
Scientists at the Mayo Clinic engineered a TIMP-1 protein variant that selectively inhibits MMP-9 and reduces invasion of triple-negative breast cancer cells, offering a promising tool for targeted cancer research.

Antibiotic sensor directly binds drug in resistant bacteria
Researchers at Drexel University uncover how the vancomycin-resistant bacterial sensor binds to the antibiotic, offering insights to guide inhibitor design that restores antibiotic effectiveness against hospital-acquired infections.

ApoA1 reduce atherosclerotic plaques via cell death pathway
Researchers show that ApoA1, a key HDL protein, helps reduce plaque and necrotic core formation in atherosclerosis by modulating Bim-driven macrophage death. The findings reveal new insights into how ApoA1 protects against heart disease.

Omega-3 lowers inflammation, blood pressure in obese adults
A randomized study shows omega-3 supplements reduce proinflammatory chemokines and lower blood pressure in obese adults, furthering the understanding of how to modulate cardiovascular disease risk.