Mild Magnetic Hyperthermia-Activated Innate Immunity for Liver Cancer Therapy.

Magnetic hyperthermia therapy (MHT) is noninvasive and features excellent tissue penetration for deep-seated tumors, but unfortunately, it suffers the low therapeutic efficacy due to the limited magneto-thermal efficiency and insufficient intratumor accumulation of conventional intravenous-injected magnetic nanoparticles, which are actually mostly sequestered by the mononuclear phagocyte system, especially the liver. Such a disadvantageous characteristic of preferential liver uptake is here exploited, for the first time as far as we know, to treat orthotopic liver cancer by mild MHT using specially designed composite magnetic nanoparticles. A kind of core-shell-structured and Zn2+-doped Zn-CoFe2O4@Zn-MnFe2O4 superparamagnetic nanoparticles (ZCMF) has been synthesized which exhibits excellent and highly controllable magnetic hyperthermia performance owing to an exchange-coupled magnetism between the core and shell, and Zn2+ doping. The controllable mild MHT at 43-44 °C based on ZCMF demonstrates almost complete inhibition of liver cancer cell proliferation and tumor growth, which is associated with the suppression of heat shock protein 70 (HSP70) expression. More importantly, the mild MHT-treated liver cancer cells are capable of activating natural killer (NK) cells by dramatically upregulating the expression of UL16-binding proteins (ULBPs), ligands of natural killer group 2 member D (NKG2D). As a result, the growth of both xenograft tumors and orthotopic liver tumors were almost completely suppressed under mild MHT via induced NK-cell-related antitumor immunity in vivo. This work not only evidences the great potential of mild MHT but also reveals the underlying immunity activation mechanism in liver cancer treatment by mild MHT.

Combined Magnetic Hyperthermia and Immune Therapy for Primary and Metastatic Tumor Treatments.

Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe2O4@MnFe2O4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.

Near-infrared laser light mediated cancer therapy by photothermal effect of Fe3O4 magnetic nanoparticles.

The photothermal effect of Fe3O4 magnetic nanoparticles is investigated for cancer therapy both in vitro and in vivo experiments. Heat is found to be rapidly generated by red and near-infrared (NIR) range laser irradiation of Fe3O4 nanoparticles with spherical, hexagonal and wire-like shapes. These Fe3O4 nanoparticles are coated with carboxyl-terminated poly (ethylene glycol)-phospholipid for enhanced dispersion in water. The surface-functionalized Fe3O4 nanoparticles can be taken up by esophageal cancer cells and do not obviously affect the cell structure and viability. Upon irradiation at 808 nm however, the esophageal cancer cell viability is effectively suppressed, and the cellular organelles are obviously damaged when incubated with the NIR laser activated Fe3O4 nanoparticles. Mouse esophageal tumor growth was found to be significantly inhibited by the photothermal effect of Fe3O4 nanoparticles, resulting in effective tumor reduction. A morphological examination revealed that after a photothermal therapy, the tumor tissue structure exhibited discontinuation, the cells were significantly shriveled and some cells have finally disintegrated.

Development of validated quantitative structure-retention relationship models for retention indices of plant essential oils.

Quantitative structure-retention relationship (QSRR) models were developed for the retention indices of 505 frequently reported components of plant essential oils. Multiple linear regression was used to build QSRR models for the dimethyl silicone, dimethyl silicone with 5% phenyl groups, and polyethylene glycol stationary phases. We tried to improve the variable selection and modeling method based on prediction method for selecting the optimum descriptors from the molecular weight, 75 topological indices, and 170 atom-type E-state indices. The three-variable QSRR models perform high correlation coefficients of 0.937 for dimethyl silicone and 0.933 for dimethyl silicone with 5% phenyl groups stationary phase. Four variables were selected to developed QSRR model for the polyethylene glycol stationary phase. The leave-one-out and leave-many-out cross-validations, bootstrapping, and y-randomization test showed the three models are robust and have no chance correlation. The external validation with the test set showed the three models present high externally predictive power. The three models presented high-quality fit, internally, and externally predictive power. It is expected that the models can effectively predict retention indices of essential oils components without experimental value.