Polymersomal Poly(I:C) Self-Magnifies Antitumor Immunity by Inducing Immunogenic Cell Death and Systemic Immune Activation.

Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond positively to the treatment. Poly(I:C) effectively triggers both innate and adaptive immunity. It is also capable of inducing immunogenic cell death (ICD) in tumor cells. However, its efficacy is hindered by its instability in vivo and limited cellular uptake. To address this, we encapsulated poly(I:C) in cRGD-targeted polymersomes (t-PPIC), which significantly increased its stability and uptake, resulting in the vital activation of dendritic cells (DCs) and apoptosis of lung tumor cells in vitro. In a murine LLC lung tumor model, systemic administration of t-PPIC effectively suppressed tumor growth and led to striking survival benefits, with 40% of the mice becoming tumor-free. Notably, t-PPIC provoked stronger apoptosis and ICD in tumor tissue and elicited a more potent stimulation of DCs, recruitment of NK cells, and activation of CD8+ T cells, compared to free poly(I:C) and nontargeted PPIC controls. Furthermore, when combined with immune checkpoint inhibitors or radiotherapy, t-PPIC amplified the antitumor immune response, resulting in complete regression in 60% of the mice. These compelling findings underscore the potential of integrin-targeted polymersomal poly(I:C) to enhance antitumor immunity by simultaneously inducing ICD and systemic immune activation. This article is protected by copyright. All rights reserved.

Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity.

The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have increasing mitochondrial oxidative phosphorylation and secrete lipid metabolites like acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM. Notably, Acar enhanced the activity of mitochondrial electron transport chain complex and mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically. Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lung metastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppresses B cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.

Simulation of dynamic monitoring for intracerebral hemorrhage based on magnetic induction phase shift technology.

Intracerebral hemorrhage (ICH) is a common and severe brain disease associated with high mortality and morbidity. Accurate measurement of the ICH area is an essential indicator for doctors to determine whether a surgical operation is necessary. However, although currently used clinical detection methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide high-quality images, they may have limitations such as high costs, large equipment size, and radiation exposure to the human body in the case of CT. It makes long-term bedside monitoring infeasible. This paper presents a dynamic monitoring method for ICH areas based on magnetic induction. This study investigates the influence of the bleeding area and the position of ICH on the phase difference at the detection point near the area to be measured. The study applies a neural network algorithm to predict the bleeding area using the phase difference data received by the detection coil as the network input and the bleeding area as the network output. The relative error between the predicted and actual values of the neural network is calculated, and the error of each group of data is less than 4%, which confirms the feasibility of this method for detecting and even trend monitoring of the ICH area.

The importance of supercooled stability for food during supercooling preservation: a review of mechanisms, influencing factors, and control methods.

Supercooling can preserve food in its original fresh state below its ice point temperature without freezing. However, the supercooled state is unstable in thermodynamics, state breakdown can occur at any moment, resulting in irregular and larger ice crystals formation, leading to food tissue damage, and loss of quality and nutrients. While the effectiveness of supercooling preservation has been verified in the lab and pilot scale tests, the stability of the supercooled state of food remains an open question, posing a limitation for larger industrial-scale application of supercooling preservation. Based on this background, this review presents the instability mechanisms of supercooling preservation and summarizes the factors such as food properties (e.g., material size, food components, specific surface area, and surface roughness) and preservation circumstances (e.g., cooling rate, temperature variation, and mechanical disturbance) that influence the stability of the supercooled state of food. The review also discusses novel techniques for enhancing the supercooling capacity and their limitations (e.g., precise temperature control and magnetic field). Further studies are necessary to comprehensively evaluate the effects of influence factors and supercooling technologies on supercooling, realizing the true sense of 'no-crystal' food products under subzero temperature preservation conditions in commercial applications.

Supercooling can maximize the potential of low temperature in food preservation.Supercooled state of food is unstable, with many factors affecting its stability.The quality of foodstuffs with supercooled failure is unacceptable.Instability of supercooling limits its large application in food industry.Novel technologies are developed to enhance the state stability of food supercooling.

Fabrication of MIL-101(Cr)/silver nanocomposites as SERS substrate for sensitive determination of malachite green and crystal violet in tilapia.

Nanocomposites with multiple functions have attracted much attention in designing novel SERS substrates. In this report, the enrichment ability of MIL-101(Cr) and the local surface plasma resonance (LSPR) of silver nanoparticles are combined to fabricate a SERS substrate denoted as MIL-101-MA@Ag, which can simultaneously produce high-density and uniformly distributed hot spots. Moreover, the enrichment ability of MIL-101(Cr) can further improve the sensitivity by concentrating and transferring the analytes in the vicinity of hot spots. Under optimal conditions, MIL-101-MA@Ag showed good SERS activity for malachite green (MG) and crystal violet (CV), with detection limits as low as 9.5×10-11 M and 9.2×10-12 M at 1616 cm-1, respectively. The prepared substrate has been successfully applied to detect MG and CV in tilapia, the recovery rate of fish tissue extract was 86.4~102%, and the relative standard deviation (RSD) was 8.9~15%. The results demonstrate that MOF-based nanocomposites are expected to be useful SERS substrates and have a universal applicability for the detection of other hazardous molecules.

Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative "cold" triple-negative breast cancer.

Triple-negative breast cancer (TNBC) due to lack of clear target and notorious "cold" tumor microenvironment (TME) is one of the most intractable and lethal malignancies. Tuning "cold" TME into "hot" becomes an emerging therapeutic strategy to TNBC. Herewith, we report that integrin-targeting micellar gemcitabine and paclitaxel (ATN-mG/P, ATN sequence: Ac-PhScNK-NH2) cooperating with polymersomal CpG (NanoCpG) effectively "heated up" and treated TNBC. ATN-mG/P exhibited greatly boosted apoptotic activity in 4T1 cells, induced potent immunogenic cell death (ICD), and efficiently stimulated maturation of bone marrow-derived dendritic cells (BMDCs). Remarkably, in a postoperative TNBC model, ATN-mG/P combining with NanoCpG promoted strong anti-cancer immune responses, showing a greatly augmented proportion of mature DCs and CD8+ T cells while reduced immune-suppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg), which led to complete inhibition of lung metastasis and 60% mice tumor-free. The co-delivery of gemcitabine and paclitaxel at desired ratio in combination with NanoCpG provides a unique platform for potent chemoimmunotherapy of "cold" tumors like TNBC.

Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia.

Acute myeloid leukemia (AML) remains a most lethal hematological malignancy, partly because of its slow development of targeted therapies compared with other cancers. PLK1 inhibitor, volasertib (Vol), is among the few molecular targeted drugs granted breakthrough therapy status for AML; however, its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits. Here, we report that transferrin-guided polymersomes (TPs) markedly augment the targetability, potency and safety of Vol to AML. Vol-loaded TPs (TPVol) with 4% transferrin exhibited best cellular uptake, effective down-regulation of p-PLK1, p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells. Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow. The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood, bone marrow, liver and spleen, effectively enhanced mouse survival rate, and impeded bone loss. This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

IL-11Rα-targeted nanostrategy empowers chemotherapy of relapsed and patient-derived osteosarcoma.

Osteosarcoma (OS) is a rare but frequently lethal bone malignancy in children and adolescents. The adjuvant chemotherapy with doxorubicin (Dox) and cisplatin remains a mainstream clinical practice though it affords only limited clinical benefits due to low tumor deposition, dose-limiting toxicity and high rate of relapse/metastasis. Here, taking advantage of high IL-11Rα expression in the OS patients, we installed IL-11Rα specific peptide (sequence: cyclic CGRRAGGSC) onto redox-responsive polymersomes encapsulating Dox (IL11-PDox) to boost the specificity and anti-OS efficacy of chemotherapy. Of note, IL-11Rα peptide at a density of 20% greatly augmented the internalization, apoptotic activity, and migration inhibition of Dox in IL-11Rα-overexpressing 143B OS cells. The active targeting effect of IL11-PDox was supported in orthotopic and relapsed 143B OS models, as shown by striking repression of tumor growth and lung metastasis, and substantial survival benefits over free Dox control. We further verified that IL11-PDox could effectively inhibit patient-derived OS xenografts. IL-11Rα-targeted nanodelivery of chemotherapeutics provides a potential therapeutic strategy for advanced osteosarcoma.

HER-2-mediated nano-delivery of molecular targeted drug potently suppresses orthotopic epithelial ovarian cancer and metastasis.

The treatment of epithelial ovarian cancer (EOC) has made slow progress due to absence of effective adjuvant chemotherapy that is capable of preventing tumor relapse and metastasis. Molecular targeted drugs such as PARP and PLK1 inhibitors appear to be promising new treatments for EOC. The low EOC cell uptake, poor selectivity and pronounced toxicity, however, greatly compromise their clinical efficacy. Herein, we report that HER-2-mediated nano-delivery of clinical PLK1-targeted drug, volasertib (Vol), while causing little toxicity potently suppresses orthotopic EOC and metastasis. Anti-HER-2 antibody, trastuzumab (Tra), was conjugated onto Vol-loaded polymersomes via click chemistry yielding Tra-PVol with a size of 33 nm and optimally about 5 Tra per polymersome. Tra-PVol exhibited clearly stronger uptake and anti-tumor activity (IC50 = 59 nM) in HER-2 overexpressing SKOV-3 cells than free Vol and non-targeted PVol controls. Both biodistribution and therapeutic studies in orthotopic SKOV-3-Luc tumor-bearing mice displayed that Tra-PVol induced significantly better tumor deposition and retardation than PVol and that intraperitoneal administration outperformed intravenous administration. More interestingly, Tra-PVol was shown to effectively suppress the intraperitoneal metastasis and to markedly prolong the survival time of SKOV-3-Luc tumor-bearing mice. This HER-2 directed molecular therapy emerges as a potential treatment strategy toward EOC.

Modeling of Chilled/Supercooled Pork Storage Quality Based on the Entropy Weight Method.

The entropy weight method (EWM) was developed and used to integrate multiple quality indexes of pork to generate a comprehensive measure of quality. The Arrhenius equation and chemical kinetic reaction were used to fit and generate the shelf life prediction model. The pork was stored at the temperatures of 7 °C, 4 °C, 1 °C and -1 °C. Quality indexes, such as drip loss, color, shear force, pH, TAC, TVB-N and TBARS were measured. The results show that low temperatures effectively delay microbial growth and lipid oxidation. The regression coefficients (R2) for the comprehensive scores at each temperature were greater than 0.973 and the activation energy Ea was 9.7354 × 104 kJ mol-1. The predicted shelf life of pork stored at 7 °C, 4 °C, 1 °C and -1 °C was 4.35 d, 6.85 d, 10.88 d and 14.90 d, respectively. In conclusion, EWM is an effective method to predict the shelf life of chilled/supercooled pork.

The Effect of Contextual Mobile Advertising on Purchase Intention: The Moderating Role of Extroversion and Neuroticism.

Contextual mobile advertising, with the advantages of high interactivity and immersive experience, is the mainstream trend of future Internet advertising. Current studies have explored the benefits of contextual mobile advertising while lacking the analysis of contextual mobile advertising factors on consumer purchase intentions. This study investigates the mechanisms by which the characteristics of contextual mobile advertising evoke consumers' purchase intentions through advertising attitudes to reveal how extroversion and neuroticism in personal traits moderate the relationship between characteristics of contextual mobile advertising and advertising attitudes. Based on a sample of 543 community residents with mobile shopping experience in China, this study uses structural equation modeling to validate the relationships between the variables and draws conclusions. The findings help advertisers to grasp the important characteristics of contextual mobile advertising, improve consumers' attitudes toward advertising, and enhance purchase intentions. Furthermore, it is possible to expand perceptions of the effectiveness of contextual mobile advertising among consumers with different personality traits.

Immunotherapy of Malignant Glioma by Noninvasive Administration of TLR9 Agonist CpG Nano-Immunoadjuvant.

Immunotherapy with toll like receptor 9 (TLR9) agonist CpG ODN offers an emergent strategy to treat life-threatening malignant glioma. CpG is typically applied invasively by intracranial and intrathecal administration which induces not only poor compliance and lessened potency but also possibly strong adverse effects and immunotoxicity. Here, it is reported that immunotherapy of murine LCPN glioma is greatly boosted by polymersome-steered intravenous and intranasal brain delivery of CpG. CpG is efficiently loaded in apolipoprotein E peptide-directed polymersomes to give blood-brain barrier permeable and glioma and cervical lymph node-homing CpG nano-immunoadjuvant (t-NanoCpG) which strongly stimulates the maturation of dendritic cells, antigen cross-presentation, and production of proinflammatory cytokines in vivo. Intriguingly, both intravenous and intranasal administration of t-NanoCpG brings about significant survival benefits in murine LCPN glioma-bearing mice while free CpG and nontargeted CpG nano-immunoadjuvant (NanoCpG) afford modest therapeutic effects. Moreover, combination of t-NanoCpG with radiotherapy further boosts the immunotherapeutic effects leading to more improved survival rate of mice. This intelligent brain-permeable nano-immunoadjuvant provides a new, minimally invasive and highly potent strategy for immunotherapy of glioma.

Folate-mediated targeted PLK1 inhibition therapy for ovarian cancer: A comparative study of molecular inhibitors and siRNA therapeutics.

PLK1 is a promising target for clinical treatment of diverse malignancies including ovarian cancer (OC), in which PLK1 over-expression is often correlated with poor prognosis and short survival. PLK1 can be blocked with small molecular inhibitors like volasertib (Vol) or silenced with PLK1-specific siRNA (siPLK1), hence effectively suppressing tumor growth. Surprisingly, despite intensive work on molecular inhibitor and siRNA therapeutics, there is no direct comparison between them reported for targeted tumor therapy. Herein, we employing folate as a ligand and polymersomes as a nanovehicle performed a comparative study on Vol and siPLK1 in inhibiting OC in vitro and in vivo. Folate-targeted polymersomal Vol and siPLK1 (termed as FA-Ps-Vol and FA-Ps-siPLK1, respectively) were both nano-sized and stable, and displayed an optimal FA density of 20% for SKOV-3 cells. Notably, FA-Ps-Vol and FA-Ps-siPLK1 exhibited an IC50 of 193 and 770 nM, respectively, to SKOV-3 cells, indicating a greater potency of Vol than siPLK1. The markedly increased uptake for FA-Ps-Vol and FA-Ps-siPLK1 compared with respective non-targeted controls by SKOV-3 tumor xenografts in mice confirmed that FA mediates strong OC-targeting in vivo. Intriguingly, FA-Ps-Vol while greatly lessening toxic effects of Vol potently repressed tumor growth with a remarkable tumor inhibition rate (TIR) of 97% at 20 mg (i.e. 32.4 µmol) Vol equiv./kg. FA-Ps-siPLK1 achieved effective tumor inhibition (TIR = ca. 87% or 90%) at 2 or 4 mg (i.e. 0.15 or 0.3 µmol) siPLK1 equiv./kg without causing adverse effects. This comparative study highlights that molecular inhibitor has the advantage of easy dose escalation and potent protein inhibition at the expense of certain adverse effects while siRNA therapeutics has low toxicity with moderate protein inhibition in vivo. STATEMENT OF SIGNIFICANCE: PLK1 is a promising target for the development of innovative and specific treatments against diverse malignancies. Interestingly, despite intensive work on molecular inhibitors and siRNA against PLK1, little work has been directed to compare their efficacy in targeted tumor therapy. Here, we employed folate as a ligand and polymersomes as a nanovehicle and have performed a comparative study on volasertib and siPLK1 in inhibiting ovarian cancer in vitro and in vivo. Our data show that the dose of volasertib can be easily escalated to induce prominent antitumor efficacy at the expense of certain adverse effects, while siPLK1 brings about moderate protein inhibition and antitumor therapy without causing toxicity at two-orders-of-magnitude lower dose.

Effect of static magnetic field extended supercooling preservation on beef quality.

Supercooling can preserve beef without freezing damage, whereas maintaining the supercooled state is difficult. An innovative method of static magnetic field extended supercooling (SM-ES) was proposed to maintain the non-frozen state of beef. Effect of SM-ES (-4 °C + SMF) compared with refrigerated (4 °C), slow-frozen (-4 °C) and frozen (-18 °C) treatment on beef quality was investigated. Results demonstrated that SM-ES successfully preserved beef at -4 °C without ice nucleation for 14 days. The SEM images revealed that the microstructure of slow-frozen/frozen samples was damaged due to crystallizing, while the ice nucleation was not observed in SM-ES treated beef. Compared with refrigerated, slow-frozen and frozen treatment, the drip loss of SM-ES decreased by 21.9%, 47.8% and 30.9%, respectively. The lipid oxidation degree of beef decreased following SM-ES treatment. SM-ES treatment extended the shelf-life of beef for more than 6 days compared with refrigeration while prevented its crystallizing.

Metabolomics of Fuzi-Gancao in CCl4 induced acute liver injury and its regulatory effect on bile acid profile in rats.

BACKGROUND: Fuzi (Radix aconiti lateralis)-Gancao (Radix glycyrrhizae) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure. AIM: To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile. METHODS: The pharmacodynamic effect of F-G on CCl4 induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver. RESULTS: Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group. CONCLUSION: F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.

A convolutional neural network algorithm for breast tumor detection with magnetic detection electrical impedance tomography.

Breast cancer is a malignant tumor disease for which early detection, diagnosis, and treatment are of paramount significance in prolonging the life of patients. Magnetic Detection Electrical Impedance Tomography (MDEIT) based on the Convolutional Neural Network (CNN), which aims to realize non-invasive, high resolution detection of breast tumors, is proposed. First, the MDEIT forward problem of the coronal and horizontal planes of the breast was simulated and solved using the Finite Element Method to obtain sample datasets of different lesions. Then, the CNN was built and trained to predict the conductivity distribution in different orientations of the breast model. Finally, noise and phantom experiments were performed in order to assess the anti-noise performance of the CNN algorithm and its feasibility of detecting breast tumors in practical applications. The simulation results showed that the reconstruction relative error with the CNN algorithm can be reduced to 10%, in comparison with the truncated singular value decomposition algorithm and back propagation algorithm. The CNN algorithm had better stability in the anti-noise performance test. When the noise of 60 dB was added, the shape of the breast tumor could still be restored by the CNN algorithm. The phantom experimental results showed that through the CNN based reconstruction algorithm, the reconstruction conductivity distribution image was legible and the position of the breast tumor could be determined. It is reasonable to conclude that the MDEIT reconstruction method proposed in this study has practical importance for the early and non-invasive detection of breast tumors.

Systemic administration of polymersomal oncolytic peptide LTX-315 combining with CpG adjuvant and anti-PD-1 antibody boosts immunotherapy of melanoma.

Oncolytic peptide LTX-315 while showing clinical promise in treating solid tumors is limited to intratumoral administration, which is not applicable for inaccessible or metastatic tumors. The cationic and amphipathic nature of oncolytic peptides engenders formidable challenges to developing systems for their systemic delivery. Here, we describe cRGD-functionalized chimaeric polymersomes (cRGD-CPs) as a robust systemic delivery vehicle for LTX-315, which in combination with CpG adjuvant and anti-PD-1 boost immunotherapy of malignant B16F10 melanoma in mice. cRGD-CPs containing 14.9 wt% LTX-315 (cRGD-CPs-L) exhibited a size of 53 nm, excellent serum stability, and strong and selective killing of B16F10 cells (versus L929 fibroblasts) in vitro, which provoked similar immunogenic effects to free LTX-315 as revealed by release of danger-associated molecular pattern molecules. The systemic administration of cRGD-CPs-L gave a notable tumor accumulation of 4.8% ID/g and significant retardation of tumor growth. More interestingly, the treatment of B16F10 tumor-bearing mice was further boosted by co-administration of polymersomal CpG and anti-PD-1 antibody, in which two out of seven mice were cured as a result of strong immune response and long-term immune memory protection. The immunotherapeutic effect was evidenced by secretion of IL-6, IFN-γ and TNF-α, tumor infiltration of CD8+ CTLs and Th, and induction of TEM and TCM in spleen. This study opens a new avenue to oncolytic peptides, which enables durable immunotherapy of tumors via systemic administration.

α3 integrin-binding peptide-functionalized polymersomes loaded with volasertib for dually-targeted molecular therapy for ovarian cancer.

Ovarian cancer (OC) is a high-mortality malignancy in women with a five-year survival rate of 30-40%. There is an urgent need to develop high-efficacy and low toxic treatments for OC. Herein, we report an appealing strategy that combines α3 integrin targeted polymersomes (A3-Ps) and targeted molecular drug, polo-like kinase 1 (PLK1) inhibitor volasertib (Vol) for dually targeted molecular therapy of OC in vivo. A3-Ps had good Vol loading of 7.7-8.0 wt.% and small size of 25-32 nm, depending on the density of α3 integrin binding peptide A3. Interestingly, cellular uptake studies using FITC-labeled Vol revealed that A3-Ps with 20% peptide gave 2.3 and 3.3-fold better internalization in SKOV-3 OC cells compared with non-targeted Ps and free Vol, respectively. Accordingly, Vol loaded in A3-Ps showed the best inhibitory activity to SKOV-3 cells with an IC50 of 49 nM, which was 3.5 times lower than free Vol. Importantly, the in vivo experiments demonstrated that A3-Ps-Vol proficiently repressed the growth of SKOV-3 tumors in mice while continuous tumor growth was observed for Ps-Vol and free Vol-treated mice. A3-Ps-Vol besides boosting anti-OC activity also reduced the systemic toxicity of Vol. This dually targeted molecular drug nanoformulation has appeared to be an especially potent and low toxic treatment modality for human ovarian cancers. STATEMENT OF SIGNIFICANCE: Volasertib provides a potential molecular therapy for PLK1-positive advanced OC patients. The initial clinical outcomes, nevertheless, showed a suboptimal efficacy, possibly resulting from its fast clearance, deficient tumor deposition and dose-limiting toxicities. Here, we show for the first time that dually targeted molecular therapy of OC using α3 integrin-binding peptide-modified polymersomes as a vehicle gives markedly improved potency, better toleration, and depleted adverse effects in SKOV-3 tumor models, greatly outperforming free volasertib. This dually targeted strategy has emerged as an appealing treatment for malignant PLK1-positive ovarian tumors.

A novel symmetrical cyclooctenone from Radix Glycyrrhizae.

A novel symmetrical structure, Gancao cyclooctenone A (1), was isolated from Radix Glycyrrhizae. The structure of the compound was established on the basis of the spectroscopic data including 1D and 2D NMR spectroscopy and mass spectrometry. Cytotoxic activities of compound 1 on A549 and Hela cell lines were evaluated and the IC50 values were determined to be 63.21 and 45.82 µΜ, respectively.

Dihydroisocoumarins from Radix Glycyrrhizae.

BACKGROUND: Radix Glycyrrhizae is the rhizome of Glycyrrhiza inflata Bat., Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L. The present paper describes the isolation and the structural elucidation of three new dihydroisocoumarins obtained from the 70% EtOH extract of Radix Glycyrrhizae. And the cytotoxic activities of these new compounds were also evaluated using four cell lines, subsequently. RESULTS: A pair of new dihydroisocoumarin epimers ((3R,4S)-4,8-dihydroxy-3-methyl-1-oxoisochroman-5-yl)methyl acetate (1) and ((3R,4R)-4,8-dihydroxy-3-methyl-1-oxoisochroman-5-yl)methyl acetate (2) along with a new dihydroisocoumarin (3R,4R)-4,8-dihydroxy-3,5-dimethylisochroman-1-one (3) were isolated from Radix Glycyrrhizae. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HR-ESI-MSand ECD calculation comparing with those of experimental CD spectra. Cytotoxic activities of the three compounds were evaluated using the HepG2, A549, LoVo and Hela cell lines, respectively. IC50 values indicated compounds 1-3 exhibited moderate or less cytotoxic activity in vitro. CONCLUSIONS: Dihydroisocoumarin is not the common components in Radix Glycyrrhizae, a series of dihydroisocoumarin were obtained in this plant could be a supplement to the chemical study of this plant.