Targeted delivery of temozolomide by nanocarriers based on folic acid-hollow TiO2 -nanospheres for the treatment of glioblastoma

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Its standard treatment includes a combination of surgery, radiation, and chemotherapy. The last involves the oral delivery of free drug molecules to GBM such as Temozolomide (TMZ). However, this treatment has limited effectiveness owing to the drugs premature degradation, lack of cell selectivity, and poor control of pharmacokinetics. In this work, the development of a nanocarrier based on hollow titanium dioxide (HT) nanospheres functionalized with folic acid (HT-FA) for the targeted delivery of temozolomide (HT-TMZ-FA) is reported. This approach has the potential benefits of prolonging TMZ degradation, targeting GBM cells, and increasing TMZ circulation time. The HT surface properties were studied, and the nanocarrier surface was functionalized with folic acid as a potential targeting agent against GBM. The loading capacity, protection from degradation, and drug retention time were investigated. Cell viability was performed to assess the cytotoxicity of HT against LN18, U87, U251, and M059K GBM cell lines. The cell internalization of HT configurations (HT, HT-FA, HT-TMZ-FA) was evaluated to study targeting capabilities against GBM cancer. Results show that HT nanocarriers have a high loading capacity, retain and protect TMZ for at least 48 h. Folic acid-functionalized HT nanocarriers successfully delivered and internalized TMZ to glioblastoma cancer cells with high cytotoxicity through autophagic and apoptotic cellular mechanisms. Thus, HT-FA nanocarriers could be a promising targeted delivery platform for chemotherapeutic drugs for the treatment of GBM cancer.