Quantitative evaluation of disc degeneration using dual-energy CT: advantages of R-VH, D-VH values and the IVNCa + CT model.

OBJECTIVE: To evaluate the correlation between dual-energy CT (DECT) virtual calcium free (VNCA), CT attenuation, the ratio and difference of VNCA to CT attenuation, and Pfirrmann grading of lumbar disc degeneration. METHODS: A retrospective analysis on 135 intervertebral discs from 30 patients who underwent DECT and MR. Discs was graded using the Pfirrmann system. ROIs on the sagittal plane assessed HU value, VNCA value, Rho value, Z value, R-VH value, and D-VH value. Correlation, grade differences, and multivariate regression models were assessed. Diagnostic performance and cut-off values were determined using AUC. RESULTS: VNCA (r = 0.589, P < 0.001), R-VH (r = 0.622, P < 0.001), and D-VH (r = 0.613, P < 0.001) moderately correlated with Pfirrmann grading. HU (r = 0.388, P < 0.001), Rho (r = 0.142, P = 0.102), and Z (r = -0.125, P = 0.153) showed a weak correlation. R-VH, D-VH, and VNCA had significantly higher correlation than HU. Statistically significant differences were observed in P values of VNCA, HU, R-VH, and D-VH in relative groups (P < 0.05), but not in Rho and Z values (P > 0.05). R-VH and D-VH had significant differences between Pfirrmann grades 1 and 2, and grades 2 and 3 (early stage) (P < 0.05). AUC readings of R-VH and D-VH (≥2, ≥3, ≥4) were higher. The multivariate model IVNCa + CT had the highest AUC. CONCLUSION: The new quantitative indices R-VH value and D-VH value of DECT have advantages over VNCA value and HU value in evaluating early-stage disc degeneration (≥2 grades, ≥3 grades). The multivariate model IVNCa + CT has the best AUC values for evaluating disc degeneration at all stages.

Fenton-like nanoparticles capable of H2O2 self-supply and glutathione consumption for chemodynamic and chemotherapy of cancer.

Chemodynamic therapy (CDT) utilizing the Fenton reaction to convert hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (˙OH) has recently drawn extensive interest in tumor treatment. However, the therapeutic efficiency of CDT often suffers from high concentrations of glutathione (GSH), insufficient endogenous H2O2 and inefficient Fenton activity. Herein, a GSH-depleting and H2O2 self-providing nanosystem that can efficiently load copper ions and doxorubicin (DOX) (MSN-Cu2+-DOX) to induce enhanced CDT and chemotherapy is proposed. The results show that MSN-Cu2+-DOX could release Cu2+ and DOX under acidic conditions. Particularly, both the released Cu2+ and Cu2+ in MSN-Cu2+-DOX are available for ˙OH production via a Fenton-like reaction for CDT. Meanwhile, Cu2+ undergoes a reduction to Cu+ by depleting overexpressed GSH, thereby enhancing CDT. Moreover, the released DOX could not only be used for chemotherapy, but also promote the generation of endogenous H2O2 to improve the efficiency of a Cu-based Fenton-like reaction. Resultantly, this nanosystem featuring Fenton-like activity, GSH consumption, H2O2 self-sufficiency and chemotherapy exhibits a great antitumor effect with a tumor inhibition ratio of 93.05%. Overall, this study provides a promising strategy to enhance CDT for effective tumor therapy.

Enzyme-Triggered Size-Switchable Nanosystem for Deep Tumor Penetration and Hydrogen Therapy.

The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H2 and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H2 to the deep part of tumors for effective gas therapy. Ammonia borane (AB) is chosen as the H2 prodrug that can be effectively loaded into UAMSN by hydrogen-bonding adsorption. Gelatin is used as the substrate of MMP-2 to trigger size change and block AB inside UAMSN during blood circulation. PEG is introduced to further increase the particle size and endow the nanoparticle with long blood circulation to achieve effective tumor accumulation via the EPR effect. After accumulation into the tumor site, MMP-2 promptly digests gelatin to expose UAMSN loading AB for deep tumor penetration. Upon stimulation by the acidic tumor microenvironment, AB decomposes into H2 for further intratumor diffusion to achieve effective hydrogen therapy. Consequently, such a simultaneous deep tumor penetration of nanocarriers and H2 results in an evident suppression on tumor growth in a 4T1 tumor-bearing model without any obvious toxicity on normal tissues. Our synthetic nanosystem provides a promising strategy for the development of nanomedicines with enhanced tumor permeability and good biosafety for efficient tumor treatment.