In Situ Growth of Columnar PEG on PEDOT and Its Antifouling Properties.

The antifouling properties of conductive polymers have received extensive attention for biosensor and bioelectronic applications. Polyethylene glycol (PEG) is a well-known antifouling material, but the controlled regulation of the surface topography of PEG without a template remains a challenge. Here, we show a columnar structure antifouling conductive polymer brush with enhanced antifouling properties and considerable conductivity. The method involves synthesizing the 3,4-ethylenedioxythiophene monomer modified with azide (EDOT-N3), the electropolymerization of PEDOT-N3, and the in situ growth of PEG polymer brushes on PEDOT through double-click reactions. The resultant columnar structure polymer brush exhibits high electrical conductivity (3.5 Ω·cm2), ultrahigh antifouling property, electrochemical stability (capacitance retention was 93.8% after 2000 cycles of CV scans in serum), and biocompatibility.

Personalized SO2 Prodrug for pH-Triggered Gas Enhancement in Anti-Tumor Radio-Immunotherapy.

The inhibition of the immune response in the tumor microenvironment by therapy regimens can impede the eradication of tumors, potentially resulting in tumor metastasis. As a non-invasive therapeutic method, radiotherapy is utilized for tumor ablation. In this study, we aimed to improve the therapeutic impact of radiotherapy and trigger an immune response by formulating a benzothiazole sulfinate (BTS)-loaded fusion liposome (BFL) nanoplatform, which was then combined with radiotherapy for anti-cancer treatment. The platelet cell membrane, equipped with distinctive surface receptors, enables BFL to effectively target tumors while evading the immune system and adhering to tumor cells. This facilitates BFL's engulfment by cancer cells, subsequently releasing BTS within them. Following the release, the BTS produces sulfur dioxide (SO2) for gas therapy, initiating the oxidation of intracellular glutathione (GSH). This process demonstrates efficacy in repairing damage post-radiotherapy, thereby achieving effective radiosensitization. It was revealed that an immune response was triggered following the enhanced radiosensitization facilitated by BFL. This approach facilitated the maturation of dendritic cell (DC) within lymph nodes, leading to an increase in the proportion of T cells in distant tumors. This resulted in significant eradication of primary tumors and inhibition of growth in distant tumors. In summary, the integration of personalized BFL with radiotherapy shows potential in enhancing both tumor immune response and the elimination of tumors, including metastasis.

Biomimetic CuS nanoparticles for radiosensitization with mild photothermal therapy and GSH-depletion.

Due to its non-invasive and highly effective characteristics, radiotherapy has attracted significant interest in cancer treatment. However, radioresistance of solid tumors caused by a unique tumor microenvironment diminishes the therapeutic effect of cancer radiotherapy. To address this issue, we developed a nanoplatform for tumor-specific targeting to improve radiotherapy. Specifically, hollow CuS nanoparticles were decorated with the platelet cell membrane (PC), endowing this nanoplatform with the therapeutic property of navigating to the tumor region for glutathione (GSH)-depletion photothermal therapy. It was discovered that mild photothermal therapy mediated by PC ameliorated hypoxia in the tumor microenvironment. Meanwhile, GSH, which contributes to repairing radiotherapy-induced DNA double-strand breaks, was depleted by PC in an acidic microenvironment. Therefore, radioresistance could be diminished while cancer cell self-repair was prevented. At therapeutic doses, PC nanoparticles have negligible toxic effects on normal tissues. PC demonstrates promise for both in vivo and in vitro radiosensitization due to its GSH-depletion, photothermal efficiency, and tumor-specific properties.

Three-dimensional deep neural network for automatic delineation of cervical cancer in planning computed tomography images.

PURPOSE: Radiation therapy is an essential treatment modality for cervical cancer, while accurate and efficient segmentation methods are needed to improve the workflow. In this study, a three-dimensional V-net model is proposed to automatically segment clinical target volume (CTV) and organs at risk (OARs), and to provide prospective guidance for low lose area. MATERIAL AND METHODS: A total of 130 CT datasets were included. Ninety cases were randomly selected as the training data, with 10 cases used as the validation data, and the remaining 30 cases as testing data. The V-net model was implemented with Tensorflow package to segment the CTV and OARs, as well as regions of 5 Gy, 10 Gy, 15 Gy, and 20 Gy isodose lines covered. The auto-segmentation by V-net was compared to auto-segmentation by U-net. Four representative parameters were calculated to evaluate the accuracy of the delineation, including Dice similarity coefficients (DSC), Jaccard index (JI), average surface distance (ASD), and Hausdorff distance (HD). RESULTS: The V-net and U-net achieved the average DSC value for CTV of 0.85 and 0.83, average JI values of 0.77 and 0.75, average ASD values of 2.58 and 2.26, average HD of 11.2 and 10.08, respectively. As for the OARs, the performance of the V-net model in the colon was significantly better than the U-net model (p = 0.046), and the performance in the kidney, bladder, femoral head, and pelvic bones were comparable to the U-net model. For prediction of low-dose areas, the average DSC of the patients' 5 Gy dose area in the test set were 0.88 and 0.83, for V-net and U-net, respectively. CONCLUSIONS: It is feasible to use the V-Net model to automatically segment cervical cancer CTV and OARs to achieve a more efficient radiotherapy workflow. In the delineation of most target areas and OARs, the performance of V-net is better than U-net. It also offers advantages with its feature of predicting the low-dose area prospectively before radiation therapy (RT).

An intratumoral injectable nanozyme hydrogel for hypoxia-resistant thermoradiotherapy.

Hypoxia in local tumors leads to the failure or resistance of radiotherapy (RT) and high-dose RT will cause systemic reactions and local radiation damage. As a non-chemotherapeutic intervention, photothermal therapy (PTT) can remove tumor tissues through thermal ablation as well as effectively improve the microenvironment of hypoxic cells. Therefore, the combined use of PTT and RT (thermoradiotherapy) has urgently become an efficient treatment. In this work, by encapsulating prussian blue (PB) nanoparticles in agarose hydrogel, we developed an injectable hybrid light-controlled hydrogel system as a PB reservoir and release controller (PRC) which can realize single injection and multiple treatments in vivo. Under the irradiation of 808 nm near-infrared (NIR) laser, PB nanoparticles convert laser energy into heat energy, causing degradation of agarose hydrogel and the release of PB nanoparticles. Due to the excellent photothermal properties of PB, photothermal treatment in the NIR Biological Windows can greatly enhance the sensitivity of tumor cells to RT. Meanwhile, PB nanoparticles can also be a nanozyme to drive the decomposition of endogenous hydrogen peroxide (H2O2), and then generate oxygen (O2) to improve the tumor hypoxic microenvironment, achieving the further enhancement of the radiation sensitivity. Notably, this study is the first design to utilize hydrogel for thermoradiotherapy. Both in vitro and in vivo experiments, the PRC demonstrated excellent effects of PTT-RT, good stability and biocompatibility, indicating our nanoplatform promote the development of anti-cancer combination thermoradiotherapy with greater clinical significance.