Abstract
Due to their ability to be engineered for specific cellular targeting, nanoparticles (NPs) have emerged as promising drug delivery vessels for immunotherapeutic and vaccination treatments. However, a major unsolved obstacle for cell-specific nanoparticle delivery is non-specific circulatory clearance by the mononuclear-phagocytic system(MPS). Comprised of various phagocytic cells, the MPS removes NPs from circulation shortly after recognition, preventing NPs from efficiently reaching their target cells and reducing the intended therapeutic effect. Although some MPS cells can serve beneficially during immunotherapy and vaccination as antigen-presenting cells (APCs) capable of priming antigen-specific immune responses, their swift clearance of NPs reduces the viability of nanotherapy in general. The most frequently employed method of enhancing NP targeting is the incorporation of targeting ligands, like antibodies and peptides, but this method has so far demonstrated minimal impact on nonspecific MPS clearance: there is currently a need for an alternative, more precise method of cell-specific NP delivery. Recently, it has been demonstrated that preferential uptake of NPs, composed of poly (ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS), by specific APC subsets can be achieved solely by modifying the NP physicochemical property of morphology. Additionally, the NP physicochemical property of surface charge has also similarly expressed the ability to alter NP biodistribution. As it has yet to be explored what the effects multiple NP physicochemical modifications in conjunction would have on NP biodistribution, I propose using PEG-bl-PPS to form NPs with various combinations of morphology and surface charge, in order to determine if the modifications can synergize to further enhance cell-specific targeting.