Physicochemical Property Effects on Immune Modulating Polymeric Nanoparticles: Potential Applications in Spinal Cord Injury

Daniel J Kolpek,1 Jaechang Kim,1 Hisham Mohammed,1 John C Gensel,2 Jonghyuck Park1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA; 2Spinal Cord and Brain Injury Research Center, Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USACorrespondence: Jonghyuck Park, Pharmaceutical Sciences, College of Pharmacy, Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, 789 S. Limestone St, Lexington, KY, 40506, USA, Tel +1 859 257 1850, Email [email protected]: Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of the immune system. To achieve this, the review delves into the roles played by innate immune cells in SCI and investigates how various NP properties influence cellular interactions and subsequent immune modulation. Key NP properties such as size, surface charge, molecular weight, shape/morphology, surface functionalization, and polymer composition are thoroughly examined. Furthermore, the review establishes connections between these properties and their effects on the immunomodulatory functions of NPs. Ultimately, this review suggests that leveraging NPs and their physicochemical properties could serve as a promising therapeutic strategy for treating SCI and potentially other inflammatory diseases.Keywords: nanomaterials, biodegradable carriers, particle engineering, biomaterial-based therapies, neuroinflammation, nerve tissue repair