Immunoliposomes (Ligand-Targeted Liposomes) Production

CD Bioparticles offers custom services to produce special bioparticles by advanced bionanotechnology. Our experienced scientists have created a comprehensive platform to synthesize different bioparticles and ensure product quality. Among these bioparticles, immunoliposome is one of the enormous potential drug targeting carrier systems.

Introduction to Immunoliposomes

Immunoliposomes are liposomes which have antibody attached to the membrane surface. The functionalization of immunoliposomes has emerged as a promising strategy for targeted delivery to and uptake by cells overexpressing the antigens to these antibodies, with a consequent reduction in side effects. Antibodies or other ligands can be attached to liposomes either before or after their preparation. Binding is achieved either covalently or noncovalently. For covalent attachment, it must be taken into consideration that the antibody molecule contains functional chemical groups. Furthermore, the sulfhydryl group plays a key role as a targeting group and has been extensively reported. Nonetheless, this group occurs infrequently in antibody molecules and must be generated by either the reduction of disulfide groups or through appropriate thiolation agents. Thiolated antibodies containing sulfhydryl groups will then react with antibodies containing a chemically reactive molecule, like a lipid-containing maleimide, forming a thioether linkage. The lipid can be synthesized prior to its incorporation into the liposome’s bilayer, and a reaction is carried out between the ligand and the anchor followed by mixing the resulting ligand with the other constituents of the liposomes. Alternatively, the anchor may be previously incorporated in the liposomal membrane and then a coupling reaction is carried out on the surface of vehicles. In addition, antibodies can be non-covalently linked to liposomes, although this strategy is less common. The reaction between biotin and neutravidin or streptavidin is particularly useful. In the process, the ligand is bound to the surface of liposomes through hydrophobic anchor with functional groups.

Immunoliposomes share the key features are as follows:

• Antibodies can be covalently and non-covalently attached to liposomes.
• The covalence of antibodies and liposomes commonly occurs between the sulfhydryl groups of thiolated antibodies and maleimide-containing liposomes.
• Immunoliposomes can target pathologic site by coupling targeting ligands to the surface of liposomes, such as monoclonal antibodies or their fragments.
• Preclinical studies evidenced selective targeting by immunoliposomes to pathologic site.

Figure.1 The structure and application of immunoliposomes (Josimar O. E., et al. Immunoliposomes: A review on functionalization strategies and targets for drug delivery. Colloids and Surfaces B: Biointerfaces. 2017）

Immunoliposomes Applications

With its specific targeting strategy, immunoliposomes have been focused on cancer therapy, inflammatory therapy and cardiovascular diseases therapy, infectious diseases therapy, and autoimmune therapy and neurodegenerative diseases therapy. Although immunoliposomes have not yet received clinical approval, the design of immunoliposomes incorporating a variety of chemotherapeutics that simultaneously exhibit specific target-cell interactions and stimuli-sensitivity has been shown a great potential to improve controlling release of drug formulations and specific targeting at the same time. And its versatile application could be found below:

• Immunoliposomes can carry contrast agent to accumulate in the target area, and help for electron paramagnetic resonance imaging and magnetic resonance imaging.
• Immunoliposomes can deliver a drug to pass the blood-brain barrier (BBB).
• Immunoliposomes is an effective way to deliver shRNA to cell and has the ability to induce gene silencing in mammalian cells.
• Immunoliposomes have been also found useful in the treatment of leukemia.
• Immunoliposomes have been applied to many other cancer types such as gastric, neuroblastoma, colorectal cancer, lung cancer, prostate cancer, and hepatic cancer.
• Immunoliposomes show an advantage in the treatment of HIV.

Figure 2. Immunoliposome-ligand-targeted liposome structure diagram.

Our Immunoliposomes Featured Services

• Liposome formulation design: we customize liposomes design based on our clients’ demand by varying lipid compositions, vesicle sizes, surface charges, etc.
• Liposome encapsulation: we employ customized protocols to encapsulate drug molecules into liposome with high encapsulation efficiency.
• Liposome-drug complex analysis and characterization: we can comprehensive analysis assays for liposomes before and after encapsulation, which includes visual appearance, size distribution, stability, Zeta potential, lamellarity, entrapment efficiency, and release rate.

Quotations and Ordering

References:
1. S. Zalipsky, et al. Polyethylene Glycol-Grafted Immunoliposomes. Journal of Controlled Release. 1996, 39: 153–61.
2. A. S. Manjappa, et al. Antibody Derivatization and Conjugation Strategies: Application in Preparation of Stealth Immunoliposome to Target Chemotherapeutics to Tumor. Journal of Controlled Release. 2011, 150: 2–22.
3. Zhang, Y., et al. In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J. Gene Med. 2003, 5: 1039-1045.
4. Mendelsohn, J., Baselga, J., Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J. Clin. Oncol. 2003, 21: 2787-2799.
5. Guin, S., Yao, H.P., Wang, M.H., RON Receptor Tyrosine Kinase as a Target for delivery of Chemodrugs by Antibody Directed Pathway for Cancer Cell Cytotoxicity. Mol. Pharm. 2009, 7: 386-397.
6. Torchilin, V. Antibody-modified liposomes for cancer chemotherapy. Expert Opin. Drug Deliv. 2008, 5: 1003-1025.
7. Clayton, R., et al. Sustained and specific in vitro inhibition of HIV-1 replication by a protease inhibitor encapsulated in gp-120 targeted liposomes. Antiviral Res. 2009, 84: 142-149.
8. Josimar O. E., et al. Immunoliposomes: A review on functionalization strategies and targets for drug delivery. Colloids and Surfaces B: Biointerfaces. 2017, http://dx.doi.org/10.1016/j.colsurfb.2017.07.085.