Year-end Sale % OFF 
Abstract
Nanomedicine has the potential to transform clinical care in the 21st century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine's translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs.
Highlights
The application of nanoparticles in medicine for disease treatment is a potentially transformative area of research
Given the diverse therapeutic potential of nano- and microscale particles, this study sought to define whether particles composed of either poly(lactic-co-glycolic acid) (PLGA) or polyethylene glycol (PEG)-derivatives induced inflammatory responses in an in vitro and in vivo setting
Our findings reveal that Particle Replication in Non-Wetting Templates (PRINT) particles do not cause any obvious activation of the innate immune response in murine macrophages or the murine lung and maintain long term (7 day) immunologic stability in the lungs of mice
Summary
The application of nanoparticles in medicine for disease treatment is a potentially transformative area of research. The possibility of potent instruction and modulation of host physiology through nanomaterials has been abundantly demonstrated These efforts include modulation of cell-specific gene expression through delivery of antisense oligonucleotides, dose-sparing and targeted delivery of pharmacologics, as well as enhanced multi-functional imaging diagnostics through nanoformulations [1,2,3]. The most obvious benefit is in the design of next-generation vaccines against microbial pathogens, whereby antigen specific immune responses can be elicited at levels far more potent than existing vaccines, commensurate with the immune response engendered by live organisms [4,5,6] These latter advances owe much to our recent understanding of the critical role of innate immunity in contextualizing an appropriate adaptive immune response. This context is triggered through endogenous host receptor signaling pathways, most well characterized by the TLR family of pattern recognition receptors (PRR), but hallmarked by a panoply of such PRRs including C-type lectin receptors, RIG-like helicases and the burgeoning understanding of Nod-like receptors (NLRs) as sentinels of the intracellular environment [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
