Side-Chain Selenium-Grafted Polymers Combining Antiangiogenesis Treatment with Photodynamic Therapy and Chemotherapy.

The abnormal tumor vasculature in solid tumors creates hypoxia and leads to compromising the delivery and anticancer efficiency of nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability might normalize tumor vessels and improve the therapeutic effect of O2-related treatment like PDT. Herein, we designed and prepared ROS-responsive side-chain selenium-grafted polymers, which had potential antiangiogenic activity, as vehicles to load photodynamic therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR irradiation, the C-Se bonds on the side chain of polymers could be cleaved in the presence of 1O2 produced by Ce6 and further formed organic selenic acid through selenoxide elimination reaction. The generated seleninic acid could downregulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released oridonin could significantly increase the intracellular ROS concentration. Both could modulate cancer cells' microenvironment to reinforce PDT. Therefore, these nanomedicines could be a good candidate for synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.

Selenium-Containing Nanoparticles Combine the NK Cells Mediated Immunotherapy with Radiotherapy and Chemotherapy.

Considering the limited clinical benefits of individual approaches against malignancy, natural killer (NK) cell-mediated immunotherapy is increasingly utilized in combination with radiotherapy and target therapeutics. However, the interplay of targeted agents, immunotherapy, and radiotherapy is complex. An improved understanding of the effect of chemotherapy or radiotherapy on specific molecular pathways in immune cells would help to optimize the synergistic antitumor efficiency. In this study, the selenium-containing nanoparticles (NPs) could deliver the chemotherapeutic drug doxorubicin (DOX) to tumor sites by systemic administration. Radiation stimuli facilitate DOX release and enhance chemotherapy efficiency. Moreover, radiation could oxidize diselenide-containing NPs to seleninic acid, which have both synergistic antitumor effect and immunomodulatory activity through enhancing NK cells function. These results indicate that the selenium-containing NPs would be a potential approach to achieve simultaneous treatments of immunotherapy, chemotherapy, and radiotherapy by a simple but effective method.

Diselenide-Containing Hyperbranched Polymer with Light-Induced Cytotoxicity.

A light-induced cytotoxicity system was fabricated using active diselenide/porphyrin-containing hyperbranched polymer aggregates in aqueous solution through emulsification. When the nanoparticles were irradiated with visible light, 1O2 was produced by the porphyrin photosensitizers in the system, which cleaved the diselenide bonds in the polymer chains and disassembled the nanosystem. Interestingly, the oxidized products exhibited cytotoxicity to the MDA-MB 231cell line without using extra anticancer drugs, which endowed the system with potential visible light-induced antitumor activity. In combination with photodynamic therapy, it is greatly anticipated that better anticancer efficacy can be achieved with this system.