Radiotherapy is a critical strategy and standard adjuvant approach to
glioblastoma treatment. One of the major challenges facing
radiotherapy is to minimize radiation damage to normal tissue without compromising
therapeutic effects on
cancer cells. Various agents and numerous approaches have been developed to improve the therapeutic index of
radiotherapy. Among them, radiosensitizers have attracted much attention because they selectively increase susceptibility of
cancer cells to radiation and thus enhance biological effectiveness of
radiotherapy. However, clinical translation of radiosensitizers has been severely limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this hindrance. In this study, a dual functional mesoporous
silica nanoparticle (MSN) formulation of the
valproic acid (VPA) radiosensitizer was developed, which specifically recognized
folic acid-overexpressing
cancer cells and released VPA conditionally in acidic turmeric microenvironment. The efficacy of this targeted and pH-responsive VPA nanocarrier was evaluated as compared to VPA treatment approach in two cell lines: rat
glioma cells C6 and human
glioma U87. Compared to VPA treatment, targeted VPA-MSNs not only potentiated the toxic effects of radiation and led to a higher rate of cell death but also enhanced inhibition on clonogenic assay. More interestingly, these effects were further accentuated by VPA-MSNs at low pH values. Western blot analysis showed that the effects were mediated via enhanced apoptosis-inducing effects. Our results suggest that the adjunctive use of VPA-MSNs may enhance the effectiveness of
radiotherapy in
glioma treatment by lowering the radiation doses required to kill
cancer cells and thereby minimize collateral damage to healthy adjacent tissue.