Lipoprotein-Based Drug Delivery Systems for Cancer Therapy

A growing body of research has harnessed the innate properties of lipoproteins as biocompatible nanocarriers for targeted cancer therapy. Lipoproteins such as high-density and low-density particles naturally traffic lipids and proteins through the bloodstream via receptor-mediated uptake. By reconstituting these carriers with cytotoxic drugs, radionuclides or nucleic acids, investigators achieve enhanced solubility, prolonged circulation and selective tumour accumulation. Lipoprotein-mimetic nanoparticles combine apolipoprotein functionalisation with synthetic lipid cores to exploit cellular entry routes—such as scavenger receptor-mediated endocytosis and macropinocytosis—and to traverse biological barriers, including the blood–brain barrier. Advances in drug loading, particle stability and receptor targeting have yielded promising preclinical results in diverse cancer models, reducing off-target effects and improving therapeutic indices. These developments underscore the potential of nature-inspired delivery platforms to transform oncology by integrating precision targeting with clinical scalability.

Research from Nature Portfolio

A foundational study described an apolipoprotein E3-reconstituted high-density lipoprotein nanostructure that exploits Ras-driven macropinocytosis to ferry siRNA across the blood–brain barrier into glioblastoma cells. Encapsulation of a calcium phosphate core carrying siRNA against anti-apoptotic targets achieved potent gene silencing, induced tumour cell apoptosis in vitro and inhibited xenograft growth. This work exemplifies the precision of leveraging endogenous lipoprotein pathways for targeted RNA interference in challenging malignancies.

Lipoprotein-Based Drug Delivery Systems for Cancer Therapy publication trend

The graph below shows the total number of articles in lipoprotein-based drug delivery systems for cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Lipoprotein: A complex of lipids and proteins that transports hydrophobic molecules through the bloodstream.

High-density lipoprotein (HDL): A small, protein-rich carrier involved in reverse cholesterol transport, repurposed for drug delivery.

Low-density lipoprotein (LDL): A larger lipid-protein particle that delivers cholesterol to cells via LDL receptors, exploited for targeted uptake.

Nanocarrier: A nanoscale delivery vehicle engineered to transport therapeutic agents selectively to diseased tissues.

siRNA: Small interfering RNA that induces sequence-specific gene silencing through the RNA interference pathway.

Macropinocytosis: A form of bulk endocytosis by which cells internalise extracellular fluid and nanoparticulate cargo.

Radiosensitiser: An agent that increases tumour cell sensitivity to ionising radiation, improving the efficacy of radiotherapy.

References

1. Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis. Nature Communications (2017).
2. Lipid nanoparticles for targeted delivery of anticancer therapeutics: Recent advances in development of siRNA and lipoprotein-mimicking nanocarriers. Advanced Drug Delivery Reviews (2023).
3. Bosutinib high density lipoprotein nanoformulation has potent tumour radiosensitisation effects. Journal of Nanobiotechnology (2023).