DEVELOPING STIMULI RESPONSIVE DEVICES FOR COMBINATION THERAPY TRIGGERED ADAPTIVE IMMUNITY AGAINST GLIOBLASTOMA

Abstract

Glioblastoma (WHO grade IV), the most frequently occurring glioma in adults, with an incidence rate of 3.22 per 100,000, has dismal prognosis with the median survival of 12-15 months after diagnosis. . The current standard of care involves maximal safe resection followed by radiotherapy in combination with chemotherapy (temozolomide). However, due to the difficulty in clearing microscopic residual disease at the margins of resection due to their proximity to the eloquent cortex, complete tumor excision remains an enormous challenge for surgical oncologists. Hence, almost all patients with glioblastoma eventually have disease relapse. In this thesis, the use of stimuli responsive delivery systems to enable site-specific on-demand customizable release of the therapeutic payload was explored. The therapeutic efficacy of the fabricated devices was evaluated using extensive 2D and 3D tumour systems and an orthotopic glioblastoma mice model.