Convection enhanced delivery of light responsive antigen capturing oxygen generators for chemo-phototherapy triggered adaptive immunity

In recent years, combination therapy has emerged as the cornerstone of clinical practice in treating glioblastoma multiforme. However, their ability to trigger and leverage body's adaptive immunity rarely been studied. Tumour heterogeneity, presence blood-brain barrier, an immunosuppressive tumor microenvironment play a crucial role 90% local recurrence post-treatment. Herein, we report improved approach capable stimulating immune response that utilizes Light responsive antigen-capturing oxygen generators (LAGs). The engineered LAGs loaded with non-genotoxic molecule, Nutlin-3a, photosensitizer, Protoporphyrin IX, can release payload on-demand when exposed light specific wavelength. in-situ generation capability enables oxygenation enhancement, thereby alleviating hypoxia enhancing efficacy chemo-photodynamic therapy. Furthermore, by modulating surface properties LAGs, demonstrated tumor-derived protein antigens released be captured retained in-situ, which improves antigen uptake presentation antigen-presenting cells. Dual drug-loaded (DD-LAGs) upregulated expression cell CD83 maturation CD86 costimulatory markers on monocyte-derived-dendritic cells, suggesting intrinsic adjuvancy. 3D printed hypoxic U87 spheroids (h-U87), DD-LAGs induced cancer death, IL-1?, downregulated IL-10 resulting CD3+, helper CD4+, cytotoxic CD8+ proliferation. Finally, have investigated convection-enhanced delivery potential route administration for DD-LAGs. Our work presents novel strategy induce death both during post-treatment, reducing possibility recurrence.