Nano magnetic liposomes-encapsulated parthenolide and glucose oxidase for ultra-efficient synergistic antitumor therapy.

Multifunctional nanoplatforms yield extremely high synergistic therapeutic effects on the basis of low biological toxicity. Based on the unique tumor microenvironment (TME), a liposomes (Lips)-based multifunctional antitumor drug delivery system known as GOD-PTL-Lips@MNPs was synthesized for chemotherapy, chemodynamic therapy (CDT), starvation therapy, and magnetic targeting synergistic therapy. Evidence has suggested that parthenolide (PTL) can induce apoptosis and consume excessive glutathione (GSH), thereby increasing the efficacy of chemodynamic therapy. On the other hand, glucose oxidase (GOD) can consume intratumoral glucose, lower pH and increase the level of H2O2 in the tumor tissue. Integrated Fe3O4 magnetic nanoparticles (MNPs) containing Fe2+ and Fe3+ effectively catalyzes H2O2 to a highly toxic hydroxyl radical (•OH) and provide magnetic targeting. During the course of in vitro and in vivo experiments, GOD-PTL-Lips@MNPs demonstrated remarkable synergistic antitumor efficacy. In particular, in mice receiving a 14 day treatment of GOD-PTL-Lips@MNPs, tumor growth was significantly inhibited, as compared with the control group. Moreover, toxicology study and histological examination demonstrated low biotoxicity of this novel therapeutic approach. In summary, our data suggests great antitumor potential for GOD-PTL-Lips@MNPs which could provide an alternative means of further improving the efficacy of anticancer therapies.

A homologous-targeting "nanoconverter" with variable size for deep tumor penetration and immunotherapy.

Tumor-associated immunosuppression, as a key barrier, prevents immunotherapy-resistant tumors. In this study, an ingenious "nanoconverter" was designed to convert immunosuppression into immunoactivation, which was a C6-ceramide (C6)-modified tumor cytomembrane-coated polydopamine-paclitaxel system (PTX/PDA@M-C6). The co-administration of C6-ceramide and tumor cytomembrane changed an adaptive immune state to an activation state, which induced a robust antigen presentation ability of tumor-infiltrating dendritic cells to activate T1 helper cells and cytotoxic T lymphocytes. Meanwhile, C6-ceramide regulated the phenotype of macrophages via the reactive oxygen species pathway, which resulted in the conversion of M2-like macrophages by infiltration within tumors into M2-like macrophages, and therefore, M2-like macrophage-mediated immunosuppression was weakened distinctly. The "nanoconverter"-mediated conversion process upregulated the expression of related immune factors including interleukin-12, interleukin-6, tumor necrosis factor-α and interferon-γ and executed positive anti-tumor effects. In addition, under the protection of tumor-homologous cytomembrane, the "nanoconverter" exhibited excellent delivery efficiency (23.22%), and subsequently, accumulated special structural "nanoconverter" could break down into smaller nanoparticles for deep penetration into the tumor tissue under a NIR laser. Ultimately, chemo/thermal therapy-assisted immunotherapy completely eliminated the tumors of tumor-bearing mice, and a potent memory response relying on effector memory T cells still persisted to protect against tumor relapse after the end of treatment. The "nanoconverter" serves as a promising nanodrug delivery system for the conversion of immunosuppression and enhanced chemo/thermal therapy. Therefore, the highly cumulative "nanoconverter" has great potential for promoting the effect and clinical application of immunotherapy.

A magnetically responsive drug-loaded nanocatalyst with cobalt-involved redox for the enhancement of tumor ferrotherapy.

Herein, cobalt-involved redox in a magnetically responsive drug-loaded nanocatalyst (PTX/Co-Lips@Fe3O4) was used to convert Fe(iii) to Fe(ii) for enhancing tumor ferrotherapy for the first time. Moreover, this work highlighted an "all in one" strategy: (1) targeting, chemotherapy, and ferrotherapy in one nanomedicine, and (2) a decrease in GSH quantity, increase in the quantity of efficient catalytic ions, and use of a magnetic field, all in one tumor ferrotherapy enhancement approach.