Pyrolyzing soft template-containing poly(ionic liquid) into hierarchical N-doped porous carbon for electroreduction of carbon dioxide

Heteroatom-doped carbon materials have demonstrated great potential in the electrochemical reduction reaction of CO2 (CO2RR) due to their versatile structure and function. However, rational structure control remains one challenge. In this work, we reported a unique carbon precursor of soft template-containing porous poly(ionic liquid) (PIL) that was directly synthesized via free-radical self-polymerization of ionic liquid monomer in a soft template route. Variation of the carbonization temperature in a direct pyrolysis process without any additive yielded a series of carbon materials with facile adjustable textural properties and N species. Significantly, the integration of soft-template in the PIL precursor led to the formation of hierarchical porous carbon material with a higher surface area and larger pore size than that from the template-free precursor. In CO2RR to CO, the champion catalyst gave a Faraday efficiency of 83.0% and a current density of 1.79 mA?cm?2 at ?0.9 V vs. reversible hydrogen electrode (vs. RHE). The abundant graphite N species and hierarchical pore structure, especially the unique hierarchical small-/ultra-micropores were revealed to enable better CO2RR performance

Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy

Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs

<i>SULF2</i> Methylation Is Associated with <i>In Vitro</i> Cisplatin Sensitivity and Clinical Efficacy for Gastric Cancer Patients Treated with a Modified FOLFOX Regimen

<div><p>Objective</p><p>Biomarkers capable of discriminating the patients who are likely to respond to certain chemotherapeutic agents could improve the clinical efficiency. The sulfatases(SULFs) play a critical role in the pathogenesis of a variety of human cancers. Here, we focused our investigation on the prognostic and predictive impact of <i>SULF2</i> methylation in gastric cancer.</p><p>Methods</p><p>Promoter CpG island methylation of <i>SULF2</i> was analyzed in 100 gastric cancer samples. The <i>in vitro</i> sensitivity to cisplatin, docetaxel, gemcitabine, irinotecan and pemetrexed were determined by histoculture drug response assay(HDRA). Additionally, 56 gastric cancer patients treated with a modified FOLFOX regimen(biweekly oxaliplatin plus 5-FU and folinic acid) were retrospectively analyzed to further evaluate the prognostic and predictive impact of <i>SULF2</i> methylation in gastric cancer.</p><p>Results</p><p>Methylated <i>SULF2</i>(<i>SULF2M</i>) was detected in 28 patients, while the remaining 72 patients showed unmethylated <i>SULF2</i>(<i>SULF2U</i>, methylation rate: 28%). Samples with <i>SULF2U</i> were more sensitive to cisplatin than those with <i>SULF2M</i>(inhibition rate: 48.80% vs. 38.15%, <i>P</i> = 0.02), while samples with <i>SULF2M</i> were more sensitive to irinotecan than <i>SULF2U</i>(inhibition rate: 53.61% vs. 40.92%, <i>P</i> = 0.01). There were no association between <i>SULF2</i> methylation and <i>in vitro</i> sensitivity to docetaxel, gemcitabine and pemetrexed. <i>SULF2</i> methylation was found to have a significant association with cisplatin efficacy(<i>SULF2M</i>: 57.14%, <i>SULF2U</i>: 80.56%, <i>P</i> = 0.02) and irinotecan efficacy(<i>SULF2M</i>: 89.29%, <i>SULF2U</i>: 62.50%, <i>P</i> = 0.01). Among the 56 patients receiving the modified FOLFOX regimen, a significant association was observed between survival and <i>SULF2</i> methylation status(<i>SULF2M:</i> 309 days, 95% CI = 236 to 382 days; <i>SULF2U:</i> 481 days, 95% CI = 418 to 490 days; <i>P</i> = 0.02). Multivariate analysis revealed that <i>SULF2</i> methylation was an independent prognostic factor of overall survival in gastric cancer patients treated with platinum-based chemotherapy.</p><p>Conclusion</p><p><i>SULF2</i> methylation is negatively associated with cisplatin sensitivity <i>in vitro</i>. <i>SULF2</i> methylation may be a novel prognostic biomarker for gastric cancer patients treated with platinum-based chemotherapy.</p></div

Descriptive statistics of investigated drugs.

<p>Descriptive statistics of investigated drugs.</p

Relationship between cut-off inhibition index and <i>in vitro</i> efficacy rate by means of HDRA.

<p>Relationship between cut-off inhibition index and <i>in vitro</i> efficacy rate by means of HDRA.</p

Association between inhibition rates of each anti-cancer agent and clinical characteristics.

<p>Data are expressed as mean ± standard deviation.</p

Patient characteristics.

<p>Patient characteristics.</p

Kaplan–Meier estimates of overall survival by <i>SULF2</i> methylation status and clinical characteristics.

<p>Kaplan–Meier estimates of overall survival by <i>SULF2</i> methylation status and clinical characteristics.</p

Univariate and multivariate Cox proportional hazard analysis of factors associated with overall survival.

<p>In this multivariate analysis, age, sex, tumor site, stage, histological grade, lymph node metastasis and <i>SULF2</i> methylation were included.</p