Natural Metallic Nanoparticles for Application in Nano-Oncology

Here, the various types of naturally synthesized metallic nanoparticles, which are essentially composed of Ce, Ag, Au, Pt, Pd, Cu, Ni, Se, Fe, or their oxides, are presented, based on a literature analysis. The synthesis methods used to obtain them most often involve the reduction of metallic ions by biological materials or organisms, i.e., essentially plant extracts, yeasts, fungus, and bacteria. The anti-tumor activity of these nanoparticles has been demonstrated on different cancer lines. They rely on various mechanisms of action, such as heat, the release of chemotherapeutic drugs under a pH variation, nanoparticle excitation by radiation, or apoptotic tumor cell death. Among these natural metallic nanoparticles, one type, which consists of iron oxide nanoparticles produced by magnetotactic bacteria called magnetosomes, has been purified to remove endotoxins and abide by pharmacological regulations. It has been tested in vivo for anti-tumor efficacy. For that, purified and stabilized magnetosomes were injected in intracranial mouse glioblastoma tumors and repeatedly heated under the application of an alternating magnetic field, leading to the full disappearance of these tumors. As a whole, the results presented in the literature form a strong basis for pursuing the efforts towards the use of natural metallic nanoparticles for cancer treatment first pre-clinically and then clinically.

Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy

Rational combinatorial therapeutic strategies have proven beneficial for the management of cancer. Recent success of checkpoint blockade in highly immunogenic tumors has renewed interest in immunotherapy. Regulatory T (T reg) cells densely populate solid tumors, which may promote progression through suppressing anti-tumor immune responses. We investigated the role of T reg cells in murine mammary carcinogenesis using an orthotopic, polyoma middle-T antigen-driven model in Foxp3DTR knockin mice. T reg cell ablation resulted in significant determent of primary and metastatic tumor progression. Importantly, short-term ablation of T reg cells in advanced spontaneous tumors led to extensive apoptotic tumor cell death. This anti-tumor activity was dependent on IFN-γ and CD4+ T cells but not on NK or CD8+ T cells. Combination of T reg cell ablation with CTLA-4 or PD-1/PD-L1 blockade did not affect tumor growth or improve the therapeutic effect attained by T reg cell ablation alone. However, T reg cell targeting jointly with tumor irradiation significantly reduced tumor burden and improved overall survival. Together, our results demonstrate a major tumor-promoting role of T reg cells in an autochthonous model of tumorigenesis, and they reveal the potential therapeutic value of combining transient T reg cell ablation with radiotherapy for the management of poorly immunogenic, aggressive malignancies.