Synthetic high-density lipoprotein-like nanoparticles for cancer therapy

Abstract

High-density lipoproteins (HDLs) are a diverse group of natural nanoparticles that are most well known for their role in cholesterol transport. However, HDLs have diverse functions that provide significant opportunities for cancer therapy. Presented is a focused review of the ways that synthetic versions of HDL have been used as targeted therapies for cancer, and as vehicles for the delivery of diverse therapeutic cargo to cancer cells. As such, synthetic HDLs are likely to play a central role in the development of next-generation cancer therapies.

Keywords:

• cancer
• cholesterol
• drug delivery
• high-density lipoprotein
• nucleic acids
• scavenger receptor

Acknowledgements

CS Thaxton would like to thank the Howard Hughes Medical Institute for a Physician-Scientist Early Career Award, grant funding from the Department of Defense/Air Force Office of Scientific Research (FA95501310192), and grant funding from the National Institutes of Health/National Cancer Institute (U54CA151880 and R01CA167041).

Financial & competing interests disclosure

CS Thaxton is a founder of AuraSense and AuraSense Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• High-density lipoproteins (HDL) are natural nanoparticles that transport cholesterol to cancer cells and can, through receptor-mediated interactions, trigger downstream signaling cascades that promote cancer progression and migration.

• Synthetic forms of HDL (HDL-like NP) have been developed to target anticancer drugs, nucleic acids and phototherapeutic compounds to cancer cells.

• New forms of HDL-like NP have been shown to serve as intrinsically therapeutic agents that can differentially modulate cellular cholesterol homeostasis, thus serving as potent cancer therapies for some types of cancer, including lymphoma.

• The production of recombinant forms of HDLs can be scaled to allow the conduct of human clinical trials.