Chris Scott 2017 PLGA-PEG-N3 targeted delivery polyscitech.PNG

A powerful tool for medicinal delivery is the use of a nanoparticle with a surface covered in a specific antibody or targeting ligand. Because these antibodies and ligands bind specifically to certain protein factors these can be tailored to target to specific cells, notably cancer cells. Since antibody bonding is a stereochemical process, shape and orientation of the antibody matters in terms of its capability to bind. If the active site of the ligand is facing inwards, towards the nanoparticle, it may not work well at all. Recently, researchers working at Queen's University Belfast, University College London, (UK) and Universidade de Lisboa (Portugal) used PLGA-PEG-Azide from PolySciTech (www.polyscitech.com, PolyVivo AI085) to generate nanoparticles which had very precisely controlled antibody orientation on their surface allowing for improved functionality and targeting. They tested this system for its ability to bind to HER2 (a factor that is overexpressed in cancer cells) and found it had substantially higher binding than a randomly oriented nanoparticle system. This research holds promise for developing a wide-array of targeted delivery systems for treating a variety of diseases, most notably cancer. Read more: M. Greene, D. A. Richards, J. Nogueira, K. Campbell, P. Smyth, M. Fernandez, C. J. Scott and V. Chudasama “Generating Next-Generation Antibody-Nanoparticle Conjugates through the Oriented Installation of Non-Engineered Antibody Fragments” Chem. Sci., 2017, DOI: 10.1039/C7SC02747H. (http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC02747H#!divAbstract)

 

  “Abstract: The successful development of targeted nanotherapeutics is contingent upon the conjugation of therapeutic nanoparticles to target-specific ligands, with particular emphasis being placed on antibody-based ligands. Thus, new methods that enable the covalent and precise installation of targeting antibodies to nanoparticle surfaces are greatly desired, especially those which do not rely on costly and time-consuming antibody engineering techniques. Herein we present a novel method for the highly controlled and oriented covalent conjugation of non-engineered antibody F(ab) fragments to PLGA-PEG nanoparticles using disulfide-selective pyridazinedione linkers and strain-promoted alkyneazide click chemistry. Exemplification of this method with trastuzumab and cetuximab showed significant improvements in both conjugation efficiency and antigen binding capability, when compared to commonly employed strategies for antibody-nanoparticle construction. This new approach paves the way for the development of antibody-targeted nanomedicines with improved paratope availability, reproducibility and uniformity to enhance both biological activity and ease of manufacture.”