Liposomes as drug carriers offer advantages such as effective payload protection, tunable carrying capacity, and improved biodistribution. However, due to functional deficiencies in targeting components and payload losses during preparation, immunoliposomes have not gained favor in commercial production.
On February 19, 2024, Lixue Wang from Nanjing University of Chinese Medicine, Yuan Wan from Binghamton University, and Luke P. Lee from Harvard University jointly published a research paper titled “Chimeric nanobody-decorated liposomes by self-assembly” in Nature Nanotechnology online. The study reported a chemically unmodified biophysical approach where chimeric nanobodies (cNBs) self-assemble into liposomal bilayers, creating immunoliposomes in a single step.
The cNBs consist of a nanobody targeting human epidermal growth factor receptor 2 (HER2), a flexible peptide linker, and a hydrophobic single transmembrane domain. Sixty-four percent of therapeutic compounds could be encapsulated within 100-nanometer liposomes, and up to 2,500 cNBs could anchor onto the liposomal membrane without steric hindrance under mild conditions. Subsequently, the study demonstrated that drug-loaded immunoliposomes enhanced cytotoxicity by 10-20 times against HER2-overexpressing cancer cell lines, inhibited the growth of xenograft tumors by 3.4 times, and increased survival rates by more than double.
Immunoliposomes offer significant payload capacity, altered pharmacokinetics, improved drug tolerance, and enhanced site-specific distribution. Despite these advantages, industrial translation faces challenges, partly due to the lack of cost-effective, scalable manufacturing technologies. Current preparation methods involve labor-intensive chemical modifications, compromising the stability of targeting components. During prolonged production, payload leakage and product losses are inevitable. Despite current efforts, these challenges persist, as high production costs and batch-to-batch variability deter manufacturers from adopting immunoliposomes. Additionally, selecting full-length antibodies, antibody fragments, or aptamers as targeting moieties presents challenges in size, biocompatibility, and stability. In contrast, small-sized, low-immunogenic, and stable nanobodies (NBs) are more suitable as targeting moieties.
The study reported a one-step strategy for preparing immunoliposomes. In essence, chimeric nanobodies (cNBs), produced in bacteria, consist of a nanobody targeting human epidermal growth factor receptor 2 (HER2), a flexible peptide linker, and a single transmembrane domain (STMD). Lipids, drugs, and cNBs self-assemble into immunoliposomes at optimal ratios. Integration of cNBs can alter the biophysical properties of liposomes. In summary, this method utilizes existing production pipelines to manufacture immunoliposomes, demonstrating potential for industrial production and clinical applications.
