Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen

Insight into Hydrogenation Selectivity of the Electrocatalytic Nitrate-to-Ammonia Reduction Reaction via Enhancing the Proton Transport

The electrocatalytic nitrate-to-ammonia reduction reaction route (NARR) is one of the emerging routes toward green ammonia synthesis, and its conversion efficiency is controlled mainly by the hydrogenation selectivity. This study proposed a likely NARR route feasible and effective even in a neutral condition. Its high catalytic selectivity and efficiency were achieved by a switch of the sulfate solution to the phosphate buffer solution (PBS), while conditions of NO3- concentration, pH, and applied potential were maintained unchanged. Specifically, the faradaic efficiencies toward NH3 (FENH3) in Na2SO4 were as low as 9.8, 19.8, and 11.4 % versus remarkably jumping to 82.8, 90.5, and 89.5 % in PBS under -0.75, -1.0, and -1.25 V, respectively. The corresponding faradaic efficiencies toward NO2- (FENO2-), 77.0, 69.2, and 73.7 % in Na2SO4, significantly dropped to10.8, 7.4, and 4.4 % in PBS, evidencing an unexpected selectivity reversal of the nitrate reduction from NO2- to NH3. This insight was further revealed by the visualization of the pH gradient near the electrode surface during NARR and confirmed by density functional theory calculations; PBS notably facilitated the proton transport and active mitigation over the proton transfer barrier. The use of PBS resulted in a maximal partial current density toward NH3 (J(NH3)) and NH3 formation rate (r(NH3)) up to 133.5 mA cm(-2) and 1.74 x 10(-7) mol s(-1) cm(-2) in 1.0 m KNO3 at -1.25 V

Establishment and validation of a prognostic nomogram for postoperative patients with gastric cardia adenocarcinoma: A study based on the Surveillance, Epidemiology, and End Results database and a Chinese cohort

Abstract Background Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. Methods In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C‐index, calibration curve, time‐dependent ROC curve, and DCA curve. Kaplan–Meier survival curves were also generated to illustrate the differences in cancer‐specific survival (CSS) between the groups. Results The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer‐specific survival in the training cohort. Both the C‐index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high‐ and low‐risk groups were observed. Conclusions Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability

Enhanced oral bioavailability and bioefficacy of phloretin using mixed polymeric modified self‐nanoemulsions

Abstract Phloretin (Ph) is a natural active ingredient with wide biological properties. However, its poor water‐solubility and low oral bioavailability limit the application significantly in functional food and drug. This study was to explore the mixed polymer Pluronic® F127 and P123 modified the different triglycerides (LCT, MCT, SCT) in self‐nanoemulsions (SNEs) for enhancing the oral bioavailability and bioefficacy of Ph. The SNEs were characterized in terms of physical property study, lipolysis study, pharmacokinetic study, and anti‐inflammatory effect. The water‐solubility of LCT‐Ph‐SNE increased 3000‐fold compared with Ph solution. Pharmacokinetic study of SNEs and other carriers (HP‐β‐CD, PVP) results indicated that LCT‐Ph‐SNE was 7.9‐fold more bioavailable compared with unformulated Ph. The anti‐inflammatory activity of LCT‐Ph‐SNE in vivo represented a 6.8‐fold enhancement compared with unformulated Ph. This novel SNE formulation may also be used for other poorly soluble ingredients with high loading capacity, which made a significant impact on functional food and drug

Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy.

To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy

Analysis of <i>TGFβR2</i> gene expression of the in NSCLC patients with Oncomine, an online survival analysis platform.

<p>A, Expression levels of <i>TGFβR2</i> in cancer vs. normal tissues derived from the Oncomine database. B, Survival analysis performed with Kaplan-Meier plots based on <i>TGFβR2</i> expression.</p

Survival analysis of chemotherapy and <i>TGFβR2</i> gene expression in NSCLC.

<p>Univariate analysis of OS (A) and DFS (B) with a Cox proportional hazards model in lung carcinoma based on chemotherapy, as determined by Cox regression estimates. Multivariate analysis of OS (C) and DFS (D) with a Cox proportional hazards model in lung carcinoma based on chemotherapy and <i>TGFβR2</i> expression, as determined by Cox regression estimates.</p