Enhanced heterogeneous interface to construct intelligent conductive hydrogel gas sensor for individualized treatment of infected wounds.

In this study, we developed an enhanced heterogeneous interface intelligent conductive hydrogel NH3 sensor for individualized treatment of infected wounds. The sensor achieved monitoring, self-diagnosis, and adaptive gear adjustment functions. The PPY@PDA/PANI(3/6) sensor had a minimum NH3 detection concentration of 50 ppb and a response value of 2.94 %. It also had a theoretical detection limit of 49 ppt for infected wound gas. The sensor exhibited a fast response time of 23.2 s and a recovery time of 42.9 s. Tobramycin (TOB) was encapsulated in a self-healing QCS/OD hydrogel formed by quaternized chitosan (QCS) and oxidized dextran (OD), followed by the addition of polydopamine-coated polypyrrole nanowires (PPY@PDA) and polyaniline (PANI) to prepare electrically conductive drug-loaded PPY@PDA/PANI hydrogels. The drug-loaded PPY@PDA/PANI hydrogel was combined with a PANI/PVDF membrane to form an enhanced heterogeneous interfacial PPY@PDA/PANI/PVDF-based sensor, which could adaptively learn the individual wound ammonia response and adjust the speed of drug release from the PPY@PDA/PANI hydrogel with electrical stimulation. Drug release and animal studies demonstrated the efficacy of the PPY@PDA/PANI hydrogel in inhibiting infection and accelerating wound healing. In conclusion, the gas-sensitive conductive hydrogel sensing system is expected to enable intelligent drug delivery and provide personalized treatment for complex wound management.

ARE-PROTACs Enable Co-degradation of an Nrf2-MafG Heterodimer.

Proteolysis-targeting chimera (PROTAC) technology has emerged as a potential strategy to degrade "undruggable" proteins in recent years. Nrf2, an aberrantly activated transcription factor in cancer, is generally considered undruggable as lacking active sites or allosteric pockets. Here, we constructed the chimeric molecule C2, which consists of an Nrf2-binding element and a CRBN ligand, as a first-in-class Nrf2 degrader. Surprisingly, C2 was found to selectively degrade an Nrf2-MafG heterodimer simultaneously via the ubiquitin-proteasome system. C2 impeded Nrf2-ARE transcriptional activity significantly and improved the sensitivity of NSCLC cells to ferroptosis and therapeutic drugs. The degradation character of ARE-PROTACs suggests that the PROTAC hijacking the transcription element of TFs could achieve co-degradation of the transcription complex.

Association of Plaque Morphology With Stroke Mechanism in Patients With Symptomatic Posterior Circulation ICAD.

OBJECTIVE: Although the main mechanisms of stroke in patients with intracranial atherosclerotic disease (ICAD) - perforating artery occlusion (PAO) and artery-to-artery embolism (AAE) - have been identified and described, relatively little is known about the morphology of the symptomatic plaques and how they differ between these two mechanisms. METHODS: We prospectively recruited patients with acute ischemic stroke in the posterior circulation that was attributable to ICAD. 51 eligible patients were enrolled and underwent magnetic resonance imaging before being assigned to the PAO or AAE group according to probable stroke mechanism. Plaque morphological properties including plaque length, lumen area, outer wall area, plaque burden, plaque surface irregularity, vessel wall remodeling, and plaque enhancement, were assessed using high-resolution magnetic resonance imaging (HRMRI). Plaque morphological parameters of both PAO and AAE groups were compared using non-parametric tests. A binary logistic regression model was used to identify independent predictors while a receiver operating characteristic curve tested the sensitivity and specificity of the model. RESULTS: Among patients who met the imaging eligibility criteria, 38 (74.5%) had PAO and 13 (25.5%) had AAE. Plaque length was shorter (6.39 [interquartile range (IQR), 5.18-7.71] mm vs 10.90 [IQR, 8.18-11.85] mm, p<0.01) in PAO patients. Plaque burden was lower in PAO group (78.00 [IQR, 71.94-86.35] % vs 86.37 [IQR, 82.24-93.04] %, p=0.04). The proportion of patients with plaque surface irregularity was higher in AAE patients than in PAO patients (19/38, 50.00% vs 12/13, 92.30%, p=0.008). Plaque length was significantly associated with the PAO mechanism (adjusted OR 0.57, 95% CI, 0.41-0.79). CONCLUSION: Intracranial atherosclerotic plaque morphology differs between patients with PAO and those with AAE. Plaque with shorter length, lower plaque burden and regular surface is more likely to cause perforating artery occlusion.

[Retracted] MicroRNA­337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing data from flow cytometric experiments in Figs. 2D and 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 3187­3196, 2017; DOI: 10.3892/or.2017.5997].

Discovery of 3,5-Dimethyl-4-Sulfonyl-1H-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability.

Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound 11 with primary Mcl-1 inhibition (52%@30 µM) led to the discovery of the most potent compound 40 with high affinity (Kd = 0.23 nM) and superior selectivity over other Bcl-2 family proteins (>40,000 folds). Mechanistic studies revealed that 40 could activate the apoptosis signal pathway in an Mcl-1-dependent manner. 40 exhibited favorable physicochemical properties and pharmacokinetic profiles (F% = 41.3%). Furthermore, oral administration of 40 was well tolerated to effectively inhibit tumor growth (T/C = 37.3%) in MV4-11 xenograft models. Collectively, these findings implicate that compound 40 is a promising antitumor agent that deserves further preclinical evaluations.

Regulation of Nrf2 by phosphorylation: Consequences for biological function and therapeutic implications.

The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.

Association of Plaque Features with Infarct Patterns in Patients with Acutely Symptomatic Middle Cerebral Artery Atherosclerotic Disease.

BACKGROUND AND PURPOSE: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns. METHODS: A single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model. RESULTS: Of 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016). CONCLUSIONS: Increased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis.

Rational Design of Conjugated Photosensitizers with Controllable Photoconversion for Dually Cooperative Phototherapy.

High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.

PEGylation of black kidney bean (Phaseolus vulgaris L.) protein isolate with potential functironal properties.

In this work, we investigated PEGylated black kidney bean protein isolates (BKBPI) by PEG succinimidyl carbonate (PEG-SC), PEG succinimidyl succinate (PEG-SS) and PEG succinimidyl propionate (PEG-SPA) conjugation. The functional properties, thermodynamic stability, in vitro digestion stability, and hemagglutination activity of the modified products were evaluated. The degree of PEGylation was measured, and FTIR analysis revealed that protein-PEG conjugations were formed, and that no obvious changes in water- and fat-holding capacities were observed. The solubility, emulsifying property, and foaming property were all improved through the modification, while, higher thermodynamic stability was achieved with the increase in Td values and reduction of ΔH. The PEGylated proteins were found to be more resistant to in vitro digestion, and the hemagglutination activity was significantly (P < 0.05) decreased, indicating the higher safety of the protein isolate. The results showed that the functional properties, thermodynamic stability, and biological safety of BKBPI were improved by PEGylation, which could serve to increase the applications for this protein.

Computed Tomography Perfusion Alberta Stroke Program Early Computed Tomography Score Is Associated with Hemorrhagic Transformation after Acute Cardioembolic Stroke.

Alberta Stroke Program Early Computed Tomography (CT) score (ASPECTS) has been applied to CT perfusion (CTP) with good interrater agreement to predict early ischemic stroke, and it can be useful in decision making in acute ischemic stroke. The aim of the present study was to assess the predictive value of CTP ASPECTS of hemorrhagic transformation (HT) in acute cardioembolic stroke. This is a single-enter, retrospective study. All patients hospitalized with acute cardioembolic stroke from January 2008 to September 2013 were included. ASPECTS of baseline non-contrast CT, CTP maps of cerebral blood volume (CBV), cerebral blood flow, and mean transit time were collected from 52 consecutive patients with less than 12-h anterior circulation ischemic stroke. MRI scan was performed within 72 h of symptom onset after index stroke including T2*-weighted gradient echo to identify HT. For bleeding risk assessment, CTP and diffusion-weighted imaging ASPECTS were categorized into 0-7 or 8-10. Baseline characteristics, ASPCETS scores and HT were compared. Eighteen (34.6%) patients had HT and four (7.7%) developed symptomatic HT. On univariate analysis, the proportion of patients with CBV-ASPECTS 0-7 was significantly higher in HT patients as compared to patients without HT (44 versus 9%, P = 0.005). CBV ASPECTS 0-7 remained independent prognostic factors for HT after adjustment for clinical baseline variables. CBV ASPECTS could be of value to predict HT risk after acute cardioembolic stroke and may be a quick risk assessment approach before reperfusion therapy.

MicroRNA­337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways.

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Tumour progression and development in CRC is a multi-step process involving a large number of genetic and epigenetic alterations. Previous studies indicated that abnormally expressed microRNAs play critical roles in CRC through regulation of oncogenic and tumour-suppressor genes. Hence, determination of the function of microRNAs may provide novel therapeutic targets for CRC diagnosis and treatments. MicroRNA­337 (miR­337) has been reported to be downregulated in several cancer types. However, the expression, function and underlying mechanisms of miR­337 in CRC have not been clearly elucidated. In this study, miR­337 was significantly decreased in CRC tissues and cell lines. Low miR­337 expression level was correlated with lymph node metastasis, distant metastasis and TNM stage of CRC patients. In addition, upregulation of miR­337 suppressed cell proliferation and invasion and promoted apoptosis in CRC. Based on bioinformatics analysis, we assumed that Kirsten rat sarcoma viral oncogene homolog (KRAS) was directly modulated by miR­337 in CRC. Luciferase reporter assay demonstrated the direct interaction between miR­337 and 3'­UTR of KRAS mRNA. Furthermore, reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that miR­337 could negatively regulate endogenous KRAS expression in CRC cells at both mRNA and protein levels. Moreover, KRAS was highly expressed in CRC tissues and inversely correlated with miR­337 expression in CRC tissues. KRAS knockdown recapitulates effects similar to those induced by miR­337 overexpression in CRC cells, whereas KRAS overexpression partially restored the tumour suppressive effects of miR­337. Besides, ectopic expression of miR­337 inactivates the AKT and ERK signalling pathways in CRC. These results suggested that miR­337 may act as a tumour suppressor during the process of CRC malignant transformation by interacting with KRAS.

Intracranial Posterior Circulation Large Artery Thrombi Visualized Using Susceptibility-Weighted MRI.

PURPOSE: To identify thrombi in patients with posterior circulation large artery occlusion using susceptibility-weighted magnetic resonance imaging (MRI). METHODS: All patients hospitalized with intracranial posterior circulation occlusion from January 2003 to September 2013 were included. MRI and computed tomography angiography were reviewed to determine the presence of arterial occlusion and identify thrombi. Eighty-one patients were analyzed to investigate susceptibility vessel sign (SVS) that was identified as blooming artifact (BA) on T2*-weighted gradient echo imaging. RESULTS: We identified 21 of 63 (33.3%) patients with BA in symptomatic patients, and 1 of 18 (5.6%) in the asymptomatic group with significant difference (P = .019). BAs were found in 6 of 10 (60.0%) patients with cardioembolism, 5 of 13 (38.5%) with dissection, 9 of 34 (26.5%) with large artery atherosclerotic disease, and 1 of 6 (16.7%) with undetermined cause. CONCLUSION: Identifying SVS may be useful in exploring the fresh thrombi and the mechanism of posterior circulation stroke.

Differentiation between adrenal adenomas and nonadenomas using dynamic contrast-enhanced computed tomography.

This study was performed to evaluate the findings including the time density curve (TD curve), the relative percentage of enhancement washout (Washr) and the absolute percentage of enhancement washout (Washa) at dynamic contrast-enhanced computed tomography (DCE-CT) in 70 patients with 79 adrenal masses (including 44 adenomas and 35 nonadenomas) confirmed histopathologically and/or clinically. The results demonstrated that the TD curves of adrenal masses were classified into 5 types, and the type distribution of the TD curves was significantly different between adenomas and nonadenomas. Types A and C were characteristic of adenomas, whereas types B, D and E were features of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma based on the TD curves were 93%, 80% and 87%, respectively. Furthermore, when myelolipomas were excluded, the specificity and accuracy for adenoma were 90% and 92%, respectively. The Washr and the Washa values for the adenomas were higher than those for the nonadenomas. The diagnostic efficiency for adenoma was highest at 7-min delay time at DCE-CT; Washr was more efficient than Washa. Washr ≥34% and Washa ≥43% were both suggestive of adenomas and, on the contrary, suspicious of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma were 84%, 77% and 81%, respectively. When myelolipomas were precluded, the diagnostic specificity and accuracy were 87% and 85%, respectively. Therefore, DCE-CT aids in characterization of adrenal tumors, especially for lipid-poor adenomas which can be correctly categorized on the basis of TD curve combined with the percentage of enhancement washout.

Susceptibility Vessel Sign in Isolated Brainstem Infarction with Large Artery Occlusion.

BACKGROUND/AIMS: It is crucial to detect the composition of the thrombus in isolated brainstem infarction with large artery occlusion. The aim of this study was to explore the susceptibility vessel sign (SVS) whose composition is mainly deoxidized red cells in patients with isolated brainstem infarction and posterior circulation large artery occlusion. METHODS: This was a single-center retrospective study. All patients with posterior circulation large artery occlusion from January 2003 to September 2013 were included. We identified 213 patients who had posterior circulation large artery occlusion, and 81 patients met the imaging eligibility criteria. Among the 81 patients, 21 had isolated brainstem infarction. RESULTS: Among the 21 patients, 7 (33%) had SVS and 2 (10%) had pseudo-SVS (calcified vessels without thrombosis). In the 7 patients with SVS, we found atrial fibrillation in 2 patients, dissection in 3 patients and large artery atherosclerotic disease (LAAD) in 2 patients. There were SVS in 100% (2/2) of patients with atrial fibrillation, 50% (3/6) of patients with dissection, and 20% (2/10) of patients with LAAD. CONCLUSIONS: SVS reflects pathology of deoxidized red cells composition in patients with isolated brainstem infarction. This finding may be useful to explore the different stroke mechanisms and therapy strategies.

Tumoral angiogenesis in both adrenal adenomas and nonadenomas: a promising computed tomography biomarker for diagnosis.

To explore the correlation between the typical findings of dynamic contrast-enhanced computed tomography (DCE-CT) and tumoral angiogenesis (microvessel density [MVD] and vascular endothelial growth factor [VEGF]) in adenomas and nonadenomas such that the enhancement mechanism of DCE-CT in adrenal masses can be explained more precisely. Forty-two patients with 46 adrenal masses confirmed by surgery and pathology were included in the study; these masses included 23 adenomas, 18 nonadenomas, and 5 hyperplastic nodules. The findings of DCE-CT and angiogenesis in adrenal masses were studied. The features of DCE-CT in adenomas and nonadenomas were evaluated to determine whether the characteristics of DCE-CT in adrenal masses were closely correlated with tumoral angiogenesis. Adrenal adenomas were significantly different from nonadenomas in the time density curve and the mean percentage of enhancement washout at the 7-minute delay time in DCE-CT. The mean MVD and VEGF expression exhibited significant differences between the rapid washout group (types A and C) and the slow washout group (types B, D, and E) and between the relative washout (Washr) ≥34% and the absolute washout (Washa) ≥43% on the 7-minute enhanced CT scans (P=0.000). Adenomas were suggested when adrenal masses presented as types A and C, and/or the Washr ≥34%, and/or the Washa ≥43%, and the opposite was suggested for nonadenomas. These results showed a close correlation between the characteristics of DCE-CT and both MVD and VEGF expression in adrenal masses. There was also a significant difference in MVD and VEGF expression between adenomas and nonadenomas. In conclusion, MVD and VEGF expression are two important pathological factors that play important roles in the characterization of DCE-CT in adrenal masses because they cause different time density curve types, the Washr and the Washa for adrenal adenomas and nonadenomas.

Fluoxetine induces vascular endothelial growth factor/Netrin over-expression via the mediation of hypoxia-inducible factor 1-alpha in SH-SY5Y cells.

Fluoxetine has become one of the most promising drugs for improving clinical outcome in patients with cerebral infarction. Although the clinical efficacy of fluoxetine has been preliminarily demonstrated, its mechanism remains unclear. Hypoxia-inducible factor 1-alpha (HIF-1α) is upstream to Netrin and vascular endothelial growth factor (VEGF), and under hypoxia conditions it may induce expression of Netrin-1 and VEGF in vascular endothelial cells. We sought to explore whether it can regulate their expression in hypoxia and mediate the effect of fluoxetine in hypoxia. In this study, the effect of hypoxia on the expression of VEGF and Netrin was observed in vitro by real-time PCR and western blotting in SH-SY5Y cells; the binding sites of HIF-1α in VEGF and Netrin gene promoters were identified by luciferase reporter; the effect of fluoxetine on binding of HIF-1α with Netrin and VEGF promoters in hypoxia was observed by Chromatin Immunoprecipitation (ChIP) Assay. We prove that HIF-1α regulates transcription of both VEGF and Netrin, and that in hypoxia fluoxetine up-regulates VEGF and Netrin expression via mediation of HIF-1α that binds to hypoxia-response element sites of VEGF and Netrin promoters. Our study indicates that HIF-1α may play an important role in the treatment of cerebral infarction through mediating the recovery of neurological function induced by fluoxetine, which provides theoretical basis for the development of gene therapeutic drugs targeting HIF-1α. We show that hypoxia-inducible factor 1-alpha (HIF-1α) regulates transcription of both vascular endothelial growth factor (VEGF) and Netrin. Furthermore, we also show that in hypoxia fluoxetine up-regulates VEGF and Netrin expression via mediation of HIF-1α that binds to hypoxia-response element (HRE) sites of VEGF and Netrin promoters. Our study indicates that HIF-1α may play an important role in the treatment of cerebral infarction through mediating the recovery of neurological function induced by fluoxetine. These findings provide a theoretical basis for development of gene therapeutic drugs targeting HIF-1α.

Magnetic resonance imaging of glioma with novel APTS-coated superparamagnetic iron oxide nanoparticles.

We report in vitro and in vivo magnetic resonance (MR) imaging of C6 glioma cells with a novel acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (Fe3O4 NPs). In the present study, APTS-coated Fe3O4 NPs were formed via a one-step hydrothermal approach and then chemically modified with acetic anhydride to generate surface charge-neutralized NPs. Prussian blue staining and transmission electron microscopy (TEM) data showed that acetylated APTS-coated Fe3O4 NPs can be taken up by cells. Combined morphological observation, cell viability, and flow cytometric analysis of the cell cycle indicated that the acetylated APTS-coated Fe3O4 NPs did not significantly affect cell morphology, viability, or cell cycle, indicating their good biocompatibility. Finally, the acetylated APTS-coated Fe3O4 nanoparticles were used in magnetic resonance imaging of C6 glioma. Our results showed that the developed acetylated APTS-coated Fe3O4 NPs can be used as an effective labeling agent to detect C6 glioma cells in vitro and in vivo for MR imaging. The results from the present study indicate that the developed acetylated APTS-coated Fe3O4 NPs have a potential application in MR imaging.

Lactobionic acid-modified dendrimer-entrapped gold nanoparticles for targeted computed tomography imaging of human hepatocellular carcinoma.

Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma.

Synthesis of PEGylated low generation dendrimer-entrapped gold nanoparticles for CT imaging applications.

Dendrimer-entrapped gold nanoparticles (Au DENPs) can be formed using low-generation dendrimers pre-modified by polyethylene glycol (PEG). The formed PEGylated Au DENPs with desirable stability, cytocompatibility, and X-ray attenuation properties enable efficient computed tomography imaging of the heart and tumor model of mice.