(NanoGlioTec) Treating Glioblastoma with Smart Nanoparticle-Embedded MiRNA and a Nanovaccine

At a glance

What is NanoGlioTec about?

Glioblastoma multiforme (GBM), the highly aggressive stage IV astrocytoma affecting the central nervous system glial cells, is the most common brain and nervous system cancer among adults, affecting 3-5 out of every 100,000 individuals. The current standard of care involves surgical resection followed by concomitant administration of radiotherapy and temozolomide, and adjuvant temozolomide after completion of radiotherapy. Daily administration of a low dose of temozolomide over time is preferred to minimize toxicity. Additionally, concomitant administration of temozolomide and radiotherapy allows for spontaneous conversion of temozolomide into its active metabolite capable of crossing the blood-brain barrier (BBB). However, in spite of a strong rationale for its development, the current standard of care still results in bleak patient outcomes, with a median survival rate of less than 20 months after diagnosis. These outcomes demand the development of novel treatment strategies.

NanoGlioTec is an exploratory proposal build up on a long-lasting active collaboration between a multi-disciplinary team of well–established researchers from Portuguese and UT Austin to develop a novel combinational multifunctional nanotechnology-
based chemo-immunotherapy against GBM.

What critical challenges is NanoGlioTec addressing?

The main goal of this exploratory project is to design a new off-the-shelf multifunctional chemo-immunotherapy based on nanomaterials to re-educate host immune response against glioblastoma (GBM). We address the hypothesis that the combination
of two nanoparticulate systems targeting (NP2) dendritic cell (DC) function and thereby increasing the recruitment of effector immune cells, while (NP1) modulating the differentiation and proliferation of GBM cells by co-deliverying miRNA mimics and the
chemotherapeutic, doxorubicin, can be an effective dual immunotherapy against GBM.

How will NanoGlioTec explore new nanotechnological approaches?

Dr. Nicholas Peppas (Austin PI) expertise in engineering, nanotechnology and mathematical modeling will be exploited to advance the properties of novel bio-responsive materials for miRNA and drug delivery, while Dr. Florindo (PI) at the University of Lisbon produced mannosylated nanoparticles (man-NP) suitable for the delivery of combinations of antigens and adjuvants. Preliminary data show the potential use of man-NP to control GBM growth and will be the starting point for DC-targeted NP in NanoGlioTNanoGlioTec is supported by nanomaterial synthetic methodologies, as well as clinically relevant GBM preclinical
models, already established at partner’s lab following ongoing collaborations. We have different sources of patient GBM, following established collaborations and ethics approvals.

How is NanoGlioTec expected to impact cancer vaccination?

NanoGlioTec represents a major advancement in the cancer vaccination field as it will at least in part overcome the limitations related to cancer antigens heterogeneity and limited presentation by improving the immunogenicity of the stressed/dying cancer cells. In addition to the overall (immune)therapeutic efficacy, we will take advantage of these 3D spheroids to answer un-open questions by dissecting the mechanisms of DC – T cells-GBM interactions within TME. NanoGlioTec will certainly open new lines of research to guide the design of effective chemo-immunotherapeutic approaches able to re-shape TME to endogenous immunity against GBM.