J. Nanotheranostics, Volume 6, Issue 3 (September 2025) – 3 articles

Background and Aim: Colorectal cancer remains a leading cause of cancer-related mortality, with growing interest in nanotechnology-driven immunotherapeutics. Gold nanoparticles (AuNPs) offer a promising platform due to their biocompatibility, functional versatility, and immunomodulatory potential. Carcinoembryonic antigens (CEAs), highly expressed in colorectal tumors, provide an ideal target for antigen-specific immune activation. The aim of this study is to evaluate the immunogenicity, biodistribution, and therapeutic efficacy of a CEA-functionalized gold nanoparticle (CEA-AuNP) construct in a mouse model of colorectal cancer following oral administration via a customized capsular delivery system. Methods: A 30-day oral administration study was performed in BALB/c mice (n = 30), who received increasing doses of CEA-AuNPs (5–50 mg/kg/day). Histological, hyperspectral imaging, and ELISA-based cytokine analyses were conducted to assess organ integrity, nanoparticle accumulation, and immune modulation. Results: CEA-AuNPs demonstrated a favorable safety profile and dose-dependent accumulation in reticuloendothelial tissues, particularly the spleen and liver. Cytokine profiling revealed enhanced IL-10 responses in the spleen, indicating anti-inflammatory immune modulation, with localized pro-inflammatory signals observed in hepatic tissue at higher doses. No signs of systemic toxicity or significant off-target effects were detected. Conclusions: The oral administration of CEA-AuNPs in healthy mice induced tissue-specific immune responses and exhibited a dose-dependent biodistribution pattern. These results support the further development of CEA-AuNPs as a nanovaccine platform for colorectal cancer immunoprophylaxis. Full article

High-Z nanoparticles (NPs) have the potential to revolutionize cancer radiotherapy by radiosensitising tumours. This is particularly important for radioresistant cancers such as glioblastoma. A newer NP candidate in this area is thulium oxide nanoparticles (TmNPs). However, prior to clinical assessment, ideal NP characteristics, including biocompatibility, biosafety, and preferential uptake in cancer, should be assessed. This in vitro study compares the effects of TmNP treatment, without radiation, on 9L gliosarcoma (9LGS), a well-established glioblastoma cell model, with exposure to Madin Darby Canine Kidney (MDCK) cells, a widely used non-cancerous cell model. The findings demonstrated selective uptake of TmNPs in 9LGS over MDCK following treatment. A biological assessment of toxicity confirmed minimal long-term effects on MDCK, whilst TmNPs were observed to induce some notable cell death in 9LGS. Excessive TmNP uptake in 9LGS over time was observed to induce cell vacuolisation, which resulted in cell death via necrosis. It was concluded that this was the explanation for the underlying mechanisms of TmNP toxicity in cancer cells. This study was therefore able to demonstrate not only that TmNPs are a biocompatible, cancer-selective candidate for radiosensitiser usage, but further provided a theory to explain its mechanisms of cancer cell toxicity. Full article

Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and infusion reactions. Here, we systematically map the temporal sequence of immune events following SPIO NW administration, including C3 opsonization, granulocyte uptake, and cytokine release. In both in vitro and in vivo models, C3 deposition occurred rapidly, peaking at approximately 5 min post-incubation or post-injection. Higher Fe/plasma ratios led to reduced C3 deposition per particle, although the absolute amount of C3 bound was greater in vivo than in vitro. Notably, C3 dissociation from the particle surface exhibited a consistent half-life of ~14 min, independent of the NW injected dose and circulation time. Immune uptake by blood granulocytes was delayed relative to opsonization, becoming prominent only at 60 min post-injection. Further, cytokine release, measured by plasma IL-6 levels, displayed an even slower profile, with peak expression at 6 h post-injection. Together, these results reveal a distinct sequential immune response to SPIO NWs: rapid C3 opsonization, delayed cellular uptake, and late cytokine response. Understanding these dynamics provides a basis for developing strategies to inhibit complement activation and improve the hemocompatibility of SPIO-based theranostic agents. Full article