Understanding the interaction between nanoparticles and immune cells is essential for the evaluation of nanotoxicity and development of nanomedicines. However, to date, there is little data on the membrane microstructure and biochemical changes in nanoparticle-loaded immune cells. In this study, we observed the microstructure of nanoparticle-loaded macrophages and changes in lipid droplets using holotomography analysis. Quantitatively analyzing the refractive index distribution of nanoparticle-loaded macrophages, we identified the interactions between nanoparticles and macrophages. The results showed that, when nanoparticles were phagocytized by macrophages, the number of lipid droplets and cell volume increased. The volume and mass of the lipid droplets slightly increased, owing to the absorption of nanoparticles. Meanwhile, the number of lipid droplets increased more conspicuously than the other factors. Furthermore, alveolar macrophages are involved in the development and progression of asthma. Studies have shown that macrophages play an essential role in the maintenance of asthma-related inflammation and tissue damage, suggesting that macrophage cells may be applied to asthma target delivery strategies. Therefore, we investigated the target delivery efficiency of gold nanoparticle-loaded macrophages at the biodistribution level, using an ovalbumin-induced asthma mouse model. Normal and severe asthma models were selected to determine the difference in the level of inflammation in the lung. Consequently, macrophages had increased mobility in models of severe asthma, compared to those of normal asthma disease. In this regard, the detection of observable differences in nanoparticle-loaded macrophages may be of primary interest, as an essential endpoint analysis for investigating nanomedical applications and immunotheragnostic strategies.

Lee DH, et al. Allergy Asthma Immunol Res. 2022 Sep;14(5):479-493. https://doi.org/10.4168/aair.2022.14.5.479

Engineered T-cell therapies, such as chimeric antigen receptor (CAR)– and T-cell receptor (TCR)–based approaches, have transformed outcomes in hematologic malignancies, yet their efficacy in solid tumors remains limited by tumor antigen escape, immunosuppressive microenvironments, and insufficient activation of CAR or TCR signaling. To overcome these barriers, we developed an intercellular adhesion molecule 1 (ICAM1)–specific chimeric costimulatory receptor (ICCR) engineered for expression in T cells to augment their activation. ICAM1 is broadly expressed across solid tumors and is further upregulated by IFNγ released during early T-cell engagement, creating a feed-forward loop that reinforces tumor recognition. ICCR engagement with ICAM1 triggered NF-κB signaling independently of TCR–peptide (p)/MHC engagement; however, full T-cell activation and cytotoxic function remained dependent on intact TCR signaling. In primary T cells, ICCR increased proliferation, cytokine production, and cytotoxicity, resulting in improved tumor control in two anaplastic thyroid cancer xenograft models treated with allogeneic or autologous ICCR-T cells. Mechanistically, ICCR strengthened tumor cell engagement, promoted selection and expansion of tumor-specific TCR clonotypes, and amplified downstream signaling pathways. These findings identify ICCR as a strategy that leverages an immune synapse–mimetic mechanism to enhance the function of low-activity tumor-specific TCRs and improve T-cell responses in solid tumor microenvironments.

Conjugate analysis of engineered T cells and IFNγ-prestimulated A375-MA2 cells

Phenotypes of RM-ATC and donor-matched primary T cells

Phenotypic analysis of engineered T cells