The effects of nanoparticle morphology, especially size and shape, on their interactions with cells are of great interest in understanding the fate of nanoparticles in biological systems and designing them for biomedical applications. While size and shape-dependent cell behavior, endocytosis mechanism, and subcellular distribution of nanoparticles have been investigated extensively with gold and other nanoparticles, studies on iron oxide nanoparticles (IONP), one of the most promising and well-thought-after nanomaterials in biomedical applications, were limited. In this study, we synthesized oligosaccharide-coated water-soluble iron oxide nanorods (IONR) with different core sizes (nm) and different aspect ratios (i.e, length/width), such as IONR_(L) at 140/6 nm and IONR _(S) at 50/7 nm as well as spherical IONP (20 nm). We investigated how their sizes and shapes affect uptake mechanisms, localization, and cell viability in different cell lines. The results from transmission electron microscopy (TEM) and confocal fluorescence microscopic imaging confirmed the internalization of these nanoparticles in different types of cells and subsequently accumulated in the subcellular compartments, such as the endosomes, and into the cytosol. Specifically, IONR_(L) exhibited the highest cell uptake compared to IONR(S) and spherical IONP, highlighted with 1.36-fold and 1.17-fold higher than that of spherical IONP in macrophages and pediatric brain tumor medulloblastoma cells, respectively. To examine the cellular uptake mechanisms preferred by the different IONR and IONP, we used different endocytosis inhibitors to block specific cellular internalization pathways when cells were treated with different nanoparticles. Results from these blocking experiments showed that IONR_(L) enters macrophage and normal kidney tissue cells through clathrin-mediated, dynamin-dependent, and macropinocytosis/phagocytosis pathways, while internalized in cancer cells primarily via clathrin/caveolae-mediated and phagocytosis mechanisms. Overall, our findings provide new insights into the further development of magnetic IONR-based imaging probes and drug delivery systems for biomedical applications.

Tumor-associated macrophages (TAMs) and dendritic cells (DCs) play pivotal roles in shaping the tumor immune microenvironment, often contributing to immunosuppression and therapy resistance. Recent advances in nanotechnology have enabled precise modulation of these immune populations, offering a promising avenue to enhance the efficacy of cancer immunotherapy. Nano-enabled platforms can reprogram TAMs from a pro-tumorigenic M2-like phenotype to an anti-tumorigenic M1-like state, thereby restoring their capacity to phagocytose tumor cells and produce pro-inflammatory cytokines. Concurrently, nanomaterials can enhance DC activation and antigen presentation, promoting robust T-cell priming and adaptive immune responses. Various nanocarriers, including liposomes, polymeric nanoparticles, and inorganic nanostructures, have been engineered to deliver immune modulators, nucleic acids, or tumor antigens selectively to TAMs and DCs within the tumor microenvironment. These strategies have demonstrated synergistic effects when combined with immune checkpoint blockade or cytokine therapy, resulting in improved tumor regression and long-term immunological memory in preclinical models. Despite these promising outcomes, challenges remain regarding nanomaterial biocompatibility, targeted delivery efficiency, and potential off-target immune activation. Ongoing research is focused on optimizing nanoparticle physicochemical properties, surface functionalization, and multi-modal delivery systems to overcome these limitations. This review highlights recent advances in nano-enabled modulation of TAMs and DCs, emphasizing mechanistic insights, therapeutic outcomes, and translational potential. By integrating nanotechnology with immunotherapy, these approaches offer a powerful strategy to overcome tumor immune evasion, paving the way for more effective and personalized cancer treatments.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma-related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotic, carbenicillin (carb), on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of Gram-positive and Gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.