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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Nanoparticle-Host Interactions: The Impact of Physiological and Pathological Factors on Biodistribution, Immune
Louay Abo Qoura1,2,3, Dmitry Kostyushev4,5,6, Alessandro Parodi7
1Research Institute of Molecular and Cellular Medicine, People's Friendship University of Russia (RUDN University), Moscow, 117198 Russia.
Background:
The clinical translation of nanoparticles (NPs) for therapeutic applications is hindered significantly by unpredictable biodistribution in diseased patients, which results from the complex interplay between engineered physicochemical properties of NPs and specific changes in the function of biological barriers.
Methods:
This review delves into the multifaceted factors that govern NP biodistribution, highlighting the critical roles of intrinsic NP design, including size, shape, and surface chemistry, along with host-specific physiological and pathological conditions. We overview how these properties can change systemic circulation, organ-specific accumulation, and clearance pathways. The role of surface functionalization in targeted delivery is examined through the lens of altered serum composition, which affects protein corona formation. Particular attention is given to immune response, whether pathogen/antigen-primed, macrophage-monocyte-mediated clearance, compromised biological barriers, and host-specific factors such as sex, age, drug exposure, and gut microbiome. Disease contexts, including cancer and viral infections, are considered to evaluate translational challenges.
Results:
NP biodistribution is shaped by the interplay between engineered physicochemical properties and disease-associated biological changes. Intrinsic NP characteristics influence systemic circulation, organ-specific accumulation, and clearance pathways. Altered serum composition affects protein corona formation and immune responses, including overactivated or suppressed immune states. Compromised biological barriers, including increased permeability of the blood-brain barrier, enhanced renal excretion, and reduced liver retention, further modify pharmacokinetic profiles. Host-specific variability and pathological conditions introduce additional complexity, creating unique barriers that passive targeting strategies often fail to overcome.
Conclusion:
Developing a comprehensive grasp of these interrelated mechanisms is crucial for engineering NPs that can translate preclinical results into expected clinical outcomes, ultimately closing the gap between research innovation and patient care.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s12195-026-00888-z.
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