Therapeutic Advances of Curcumin and Nanocurcumin in Glioblastoma: Molecular Targets, Bioavailability, and Drug Delivery

Glioblastoma (GBM), the most common, invasive, and chemoresistant form of adult primary brain cancer, is characterized by rapid cell proliferation, local invasiveness, and resistance to chemotherapy (e.g., temozolomide (TMZ)) and radiation therapy. Curcumin, a bioactive polyphenol derived from <i>Curcuma longa</i>, has exhibited exceptional anti-cancer properties, including anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic activities in a wide range of cancer models, including GBM. However, the clinical application of curcumin has been seriously limited by several challenges, including low water solubility, low bioavailability, rapid systemic clearance, and poor blood-brain barrier (BBB) penetration. To overcome these challenges, several nanocarrier systems to produce nanocurcumin have been developed, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and micelles. These nanoformulations improve the solubility, stability, systemic circulation, and target-directed delivery of curcumin to glioma cells, thereby resulting in a high level of accumulation in the glioma microenvironment. On the other hand, this work is devoted to the potential of curcumin and nanocurcumin for the treatment of GBM. The article provides a detailed review of the major molecular targets of curcumin, such as NF-κB, STAT3, PI3K/AKT/mTOR, and p53 signaling pathways, as well as recent advancements in nanotechnology-based delivery platforms that improve drug delivery across the BBB and their possible clinical translation. We also include a thorough examination of the issues, limitations, and potential opportunities associated with the clinical advancement of curcumin-based therapeutics for GBM.