A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma

by Selleckchem | Mar 26 2023

The major challenges of immunotherapy for glioblastoma are that drugs cannot target tumor sites accurately and properly activate complex immune responses. Herein, we design and prepare a kind of chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug (Lonidamine modified with mitochondrial targeting agent triphenylphosphine, TLND). Reactive oxygen species and inducible nitric oxide synthase (ROS/iNOS), which are specifically highly expressed in glioblastoma microenvironment, are used as chemoattractants to induce the chemotactic behavior of the nanomotors. We propose a precise targeting strategy of brain endothelial cells-tumor cells-mitochondria. Results verified that the released NO and TLND can regulate the immune circulation through multiple steps to enhance the effect of immunotherapy, including triggering the immunogenic cell death of tumor, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment. Moreover, this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence.

Comments：

Your proposed approach seems promising in overcoming some of the major challenges associated with immunotherapy for glioblastoma. By designing a chemotactic nanomotor that targets brain endothelial cells and tumor cells and is loaded with a mitochondrial-targeted anti-tumor drug, you have created a precise targeting strategy that could potentially enhance the effect of immunotherapy.

The use of ROS/iNOS as chemoattractants to induce the chemotactic behavior of the nanomotors is a clever approach that takes advantage of the unique characteristics of the glioblastoma microenvironment. This approach has the potential to increase the specificity of drug delivery and reduce off-target effects.

The proposed treatment strategy of releasing NO and TLND to regulate immune circulation through multiple steps to enhance the effect of immunotherapy is also intriguing. By triggering immunogenic cell death of tumor cells, inducing dendritic cells to mature, promoting cytotoxic T cells infiltration, and regulating tumor microenvironment, this approach has the potential to enhance the immune response against glioblastoma and improve patient outcomes.

Moreover, the fact that this treatment strategy can form an effective immune memory effect to prevent tumor metastasis and recurrence is particularly exciting. The ability to prevent tumor recurrence is a major challenge in the treatment of glioblastoma, and any approach that can improve long-term outcomes is highly desirable.

Overall, your proposed approach has the potential to overcome some of the major challenges associated with immunotherapy for glioblastoma and improve patient outcomes. However, further research is needed to fully evaluate the safety and efficacy of this approach in preclinical and clinical trials.