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Dual Functional Mesoporous Silicon Nanoparticles Enhance the Radiosensitivity of VPA in Glioblastoma 1

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Effect of VPA, MSNs, and VPA-MSNs on C6 and U87 glioma cell viability. C6 and U87 gliomas were treated with various concentrations of VPA, MSNs, and VPA-MSNs for 12 or 24 hours, and cell viability were examined with MTT assay. Cell viability was calculated relative to untreated controls.
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f0015: Effect of VPA, MSNs, and VPA-MSNs on C6 and U87 glioma cell viability. C6 and U87 gliomas were treated with various concentrations of VPA, MSNs, and VPA-MSNs for 12 or 24 hours, and cell viability were examined with MTT assay. Cell viability was calculated relative to untreated controls.

Mentions: To examine the effects of MSNs and VPA-MSNs on cell viability, C6 and U87 cells were treated with serial dilutions of VPA, MSNs, and VPA-MSNs (12.5, 25, 50, and 100 mg/ml) for 12 and 24 hours, respectively. As shown in Figure 3 and Table 1, MSNs and VPA-MSNs in either 10- or 100-mg/l concentrations did not induce remarkable cytotoxicity on C6 and U87 glioma cells.


Dual Functional Mesoporous Silicon Nanoparticles Enhance the Radiosensitivity of VPA in Glioblastoma 1
Effect of VPA, MSNs, and VPA-MSNs on C6 and U87 glioma cell viability. C6 and U87 gliomas were treated with various concentrations of VPA, MSNs, and VPA-MSNs for 12 or 24 hours, and cell viability were examined with MTT assay. Cell viability was calculated relative to untreated controls.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304234&req=5

f0015: Effect of VPA, MSNs, and VPA-MSNs on C6 and U87 glioma cell viability. C6 and U87 gliomas were treated with various concentrations of VPA, MSNs, and VPA-MSNs for 12 or 24 hours, and cell viability were examined with MTT assay. Cell viability was calculated relative to untreated controls.
Mentions: To examine the effects of MSNs and VPA-MSNs on cell viability, C6 and U87 cells were treated with serial dilutions of VPA, MSNs, and VPA-MSNs (12.5, 25, 50, and 100 mg/ml) for 12 and 24 hours, respectively. As shown in Figure 3 and Table 1, MSNs and VPA-MSNs in either 10- or 100-mg/l concentrations did not induce remarkable cytotoxicity on C6 and U87 glioma cells.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus