Magnetic nanoparticles (MNPs) have shown promising features to be utilized in combinatorial magnetic hyperthermia and chemotherapy. Here, we assessed if a thermo-chemotherapeutic approach consisting of the intratumoral application of functionalized chitosan-coated MNPs (CS-MNPs) with 5-fluorouracil (5FU) and magnetic hyperthermia prospectively improves the treatment of colorectal cancer. With utilization of a human colorectal cancer (HT29) heterotopic tumor model in mice, we showed that the thermo-chemotherapeutic treatment is more efficient in inactivating colon cancer than either tumor treatments alone (i.e., magnetic hyperthermia vs. the presence of 5FU attached to MNPs). In particular, the thermo-chemotherapeutic treatment significantly (p < 0.01) impacts tumor volume and tumor cell proliferation (Ki67 expression, p < 0.001) compared to the single therapy modalities. The thermo-chemotherapeutic treatment: (a) affects DNA replication and repair as measured by H2AX and phosphorylated H2AX expression (p < 0.05 to 0.001), (b) it does not distinctly induce apoptosis nor necroptosis in target cells, since expression of p53, PARP cleaved-PARP, caspases and phosphorylated-RIP3 was non-conspicuous, (c) it renders tumor cells surviving therapy more sensitive to further therapy sessions as indicated by an increased expression of p53, reduced expression of NF-κB and HSPs, albeit by tendency with p > 0.05), and (d) that it impacts tumor vascularity (reduced expression of CD31 and αvβ3 integrin (p < 0.01 to 0.001) and consequently nutrient supply to tumors. We further hypothesize that tumor cells die, at least in parts, via a ROS dependent mechanism called oxeiptosis. Taken together, a very effective elimination of colon cancers seems to be feasible by utilization of repeated thermo-chemotherapeutic therapy sessions in the long-term.

The current study introduces, for the first time, a possible prognostic value of SORCIN in childhood ALL, which may be correlated with MDR1/P-gp gene expression in these patients.

Taken together, these data suggest that dietary omega-3 may improve cognitive function and provide a potential therapy for memory impairment due to neuroinflammation.

Magnetic nanoparticles (MNPs) are prone to exhibit physicochemical changes caused by their interaction with biological solutions. However, such interactions have been less considered in cancer therapy studies. The behavior of four iron oxide MNP formulations with different surface coatings, namely, chitosan (CS), polyvinyl alcohol (PVA), carboxymethyldextran (CMX), and polydimethylamine (PEA), was investigated, after their exposure to four different cell culture media (DMEM/F12 and MEM, among others) and six different cancer cell lines (HT29, HT1080, T24, MDA-MB-231, BxPC-3, and LS174T). The sedimentation (Vs) and diffusion (Vd) velocities of MNPs in different culture media were calculated. Atomic absorption spectroscopy (AAS) and dynamic light scattering (DLS) were used to quantify cell uptake efficiency and physicochemical properties, respectively. Apart from PVA-coated MNPs, CMX-, CS-, and PEA-coated MNPs clustered and increased notably in size when dispensed in culture media. The different MNP formulations led either to a low (PVA-coated MNPs), medium (CS- and CMX-coated MNPs), or high (PEA-coated MNPs) clustering in the different culture media. Clustering correlated with the Vs and Vd of the MNPs and their subsequent interaction with cells. In particular, the CMX-coated MNPs with higher Vs and lower Vd internalized more readily than the PVA-coated MNPs into the different cell lines. Hence, our results highlight key considerations to include when validating nanoparticles for future biomedical applications.