Particle Targeting in Complex Biological Media

Abstract

Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e.g., a protein corona) changes the properties of the carriers and can render their behavior unpredictable. For this reason, it is of importance to consider the potential challenges imposed by the biological environment at the early stages of particle design. This review describes parameters that affect the targeting ability of particulate drug carriers, with an emphasis on the effect of the protein corona. We highlight strategies for exploiting the protein corona to improve the targeting ability of particles. Finally, we provide suggestions for complementing current in vitro assays used for the evaluation of targeting and carrier efficacy with new and emerging techniques (e.g., 3D models and flow‐based technologies) to advance fundamental understanding in bio‐nano science and to accelerate the development of targeted particles for biomedical applications.

Formation of a Monolayer Protein Corona around Polystyrene Nanoparticles and Implications for Nanoparticle Agglomeration

“…To conclude, we have characterized protein corona formation on PS‐NPs using systematic variation of the protein concentration and ionic strength of the solvent. We have chosen Tf and HSA as model proteins because they are often used in efforts to engineer nanoparticle‐based drug carriers . Thus, we expect that our results and their implications can give guidance to researchers developing NPs for biomedical applications, where these effects can be exploited to control the properties of the protein corona by proper choice of the composition (ionic strength, protein types, and concentration) of the immersion fluid.…”

“…NPs are of similar size as biomolecular complexes and, therefore, perfectly capable of interacting with the molecular machinery of life. However, to ensure both efficacy and safety of NPs in biomedical applications, their interactions with the biological environment have to be thoroughly examined …”

Elected to the Royal Society: P. L. Arnold, M. A. Brimble, F. Caruso, R. S. Goody, R. H. Crabtree, C. Bertozzi, J. Sauer / Jochen Block Prize: A. Vorholt / Otto Bayer Award: T. Erb

“…Caruso's research is centered on the interactions between nanostructured materials and biological systems, with a particular focus on engineering particle‐based systems to modulate biological responses. He has recently discussed particle targeting in complex biological media in a Review in Advanced Healthcare Materials , and has published an Editorial in Angewandte Chemie on robust chemistry . Caruso is on the International Advisory Board of Angewandte Chemie as well as the advisory boards of Advanced Functional Materials , Advanced Healthcare Materials , and Advanced Science .…”

Nanoengineering of Poly(ethylene glycol) Particles for Stealth and Targeting

“…These include the transition of the concept of the "protein corona" to the "biomolecular corona" 21-23 and the emerging understanding of the complex interplay between particle properties, particle ligands, and the dynamic biological environment. [24][25][26][27] Though these advances have increased our understanding, they have also introduced new challenging questions. Poly(ethylene glycol) (PEG)-one of the most commonly used "stealth" coatings-has been widely used to functionalize nanocarriers (e.g., PEGylated micelles, 28 liposomes, 29 and poly(lactic-co-glycolic acid) particles 30,31 ) for reducing nonspecific interactions.…”