Radiofrequency enhances drug release from responsive nanoflowers for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe3O4 NCs), - CUR layer, - and MnO2 (CUR-Fe@MnO2 NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO2 NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO2 NFs to release Mn2+ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO2 NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO2 NFs were effective T 1/T 2 contrast agents for molecular magnetic resonance imaging due to the release of Mn2+ and Fe3O4 NCs.

Reference Ranges of Ventricular Morphology and Function in Healthy Chinese Adults: A Multicenter 3 T MRI Study.

BACKGROUND: Magnetic resonance imaging (MRI) reference ranges for ventricular morphology and function in the Chinese population are lacking. PURPOSE: To establish the MRI reference ranges of left and right ventricular (LV and RV) morphology and function based on a large multicenter cohort. STUDY TYPE: Prospective. POPULATION: One thousand and twelve healthy Chinese Han adults. FIELD STRENGTH/SEQUENCE: Balanced steady-state free procession cine sequence at 3.0 T. ASSESSMENT: Biventricular end-diastolic, end-systolic, stroke volume, and ejection fraction (EDV, ESV, SV, and EF), LV mass (LVM), end-diastolic and end-systolic dimension (LVEDD and LVESD), anteroseptal wall thickness (AS), and posterolateral wall thickness (PL) were measured. Body surface area (BSA) and height were used to index biventricular parameters. Parameters were compared between age groups and sex. STATISTICAL TESTS: Independent-samples t-tests or Mann-Whitney U test to compare mean values between sexes; ANOVA or Kruskal-Wallis test to compare mean values among age groups; linear regression to assess the relationships between cardiac parameters and age (correlation coefficient, r). A P value <0.05 was considered statistically significant. RESULTS: The biventricular volumes, LVM, LVEDD, RVEDV/LVEDV ratio, LVESD, AS, and PL were significantly greater in males than in females, even after indexing to BSA or height, while LVEF and RVEF were significantly lower in males than in females. For both sexes, age was significantly negatively correlated with biventricular volumes (male and female: LVEDV [r = -0.491; r = -0.373], LVESV [r = -0.194; r = -0.184], RVEDV [r = -0.639; r = -0.506], RVESV [r = -0.270; r = -0.223]), with similar correlations after BSA normalization. LVEF (r = 0.043) and RVEF (r = 0.033) showed a significant correlation with age in females, but not in males (P = 0.889; P = 0.282). DATA CONCLUSION: MRI reference ranges for biventricular morphology and function in Chinese adults are presented and show significant associations with age and sex. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Reference ranges of myocardial T1 and T2 mapping in healthy Chinese adults: a multicenter 3T cardiovascular magnetic resonance study.

BACKGROUND: Although reference ranges of T1 and T2 mapping are well established for cardiovascular magnetic resonance (CMR) at 1.5T, data for 3T are still lacking. The objective of this study is to establish reference ranges of myocardial T1 and T2 based on a large multicenter cohort of healthy Chinese adults at 3T CMR. METHODS: A total of 1015 healthy Chinese adults (515 men, age range: 19-87 years) from 11 medical centers who underwent CMR using 3T Siemens scanners were prospectively enrolled. T1 mapping was performed with a motion-corrected modified Look-Locker inversion recovery sequence using a 5(3)3 scheme. T2 mapping images were acquired using T2-prepared fast low-angle shot sequence. T1 and T2 relaxation times were quantified for each slice and each myocardial segment. The T1 mapping and extracellular volume standardization (T1MES) phantom was used for quality assurance at each center prior to subject scanning. RESULTS: The phantom analysis showed strong consistency of spin echo, T1 mapping, and T2 mapping among centers. In the entire cohort, global T1 and T2 reference values were 1193 ± 34 ms and 36 ± 2.5 ms. Global T1 and T2 values were higher in females than in males (T1: 1211 ± 29 ms vs. 1176 ± 30 ms, p < 0.001; T2: 37 ± 2.3 ms vs. 35 ± 2.5 ms, p < 0.001). There were statistical differences in global T2 across age groups (p < 0.001), but not in global T1. Linear regression showed no correlation between age and global T1 or T2 values. In males, positive correlation was found between heart rate and global T1 (r = 0.479, p < 0.001). CONCLUSIONS: Using phantom-validated imaging sequences, we provide reference ranges for myocardial T1 and T2 values on 3T scanners in healthy Chinese adults, which can be applied across participating sites. Trial registration URL: http://www.chictr.org.cn/index.aspx . Unique identifier: ChiCTR1900025518. Registration name: 3T magnetic resonance myocardial quantitative imaging standardization and reference value study: a multi-center clinical study.

An overview of the material science and knowledge of nanomedicine, bioscaffolds, and tissue engineering for tendon restoration.

Tendon wounds are a worldwide health issue affecting millions of people annually. Due to the characteristics of tendons, their natural restoration is a complicated and lengthy process. With the advancement of bioengineering, biomaterials, and cell biology, a new science, tissue engineering, has developed. In this field, numerous ways have been offered. As increasingly intricate and natural structures resembling tendons are produced, the results are encouraging. This study highlights the nature of the tendon and the standard cures that have thus far been utilized. Then, a comparison is made between the many tendon tissue engineering methodologies proposed to date, concentrating on the ingredients required to gain the structures that enable appropriate tendon renewal: cells, growth factors, scaffolds, and scaffold formation methods. The analysis of all these factors enables a global understanding of the impact of each component employed in tendon restoration, thereby shedding light on potential future approaches involving the creation of novel combinations of materials, cells, designs, and bioactive molecules for the restoration of a functional tendon.

Research progress on the therapeutic effects of nanoparticles loaded with drugs against atherosclerosis.

Presently, there are many drugs for the treatment of atherosclerosis (AS), among which lipid-lowering, anti-inflammatory, and antiproliferative drugs have been the most studied. These drugs have been shown to have inhibitory effects on the development of AS. Nanoparticles are suitable for AS treatment research due to their fine-tunable and modifiable properties. Compared with drug monotherapy, experimental results have proven that the effects of nanoparticle-encapsulated drugs are significantly enhanced. In addition to nanoparticles containing a single drug, there have been many studies on collaborative drug treatment, collaborative physical treatment (ultrasound, near-infrared lasers, and external magnetic field), and the integration of diagnosis and treatment. This review provides an introduction to the therapeutic effects of nanoparticles loaded with drugs to treat AS and summarizes their advantages, including increased targeting ability, sustained drug release, improved bioavailability, reduced toxicity, and inhibition of plaque and vascular stenosis.

Recent progress in cancer cell membrane-based nanoparticles for biomedical applications.

Immune clearance and insufficient targeting have limited the efficacy of existing therapeutic strategies for cancer. Toxic side effects and individual differences in response to treatment have further limited the benefits of clinical treatment for patients. Biomimetic cancer cell membrane-based nanotechnology has provided a new approach for biomedicine to overcome these obstacles. Biomimetic nanoparticles exhibit various effects (e.g., homotypic targeting, prolonging drug circulation, regulating the immune system, and penetrating biological barriers) after encapsulation by cancer cell membranes. The sensitivity and specificity of diagnostic methods will also be improved by utilizing the properties of cancer cell membranes. In this review, different properties and functions of cancer cell membranes are presented. Utilizing these advantages, nanoparticles can exhibit unique therapeutic capabilities in various types of diseases, such as solid tumors, hematological malignancies, immune system diseases, and cardiovascular diseases. Furthermore, cancer cell membrane-encapsulated nanoparticles show improved effectiveness and efficiency in combination with current diagnostic and therapeutic methods, which will contribute to the development of individualized treatments. This strategy has promising clinical translation prospects, and the associated challenges are discussed.

PPy-Coated Mo3S4/CoMo2S4 Nanotube-like Heterostructure for High-Performance Lithium Storage.

Heterostructured materials show great potential to enhance the specific capacity, rate performance and cycling lifespan of lithium-ion batteries owing to their unique interfaces, robust architectures, and synergistic effects. Herein, a polypyrrole (PPy)-coated nanotube-like Mo3S4/CoMo2S4 heterostructure is prepared by the hydrothermal and subsequent in situ polymerization methods. The well-designed nanotube-like structure is beneficial to relieve the serious volume changes and facilitate the infiltration of electrolytes during the charge/discharge process. The Mo3S4/CoMo2S4 heterostructure could effectively enhance the electrical conductivity and Li+ transport kinetics owing to the refined energy band structure and the internal electric field at the heterostructure interface. Moreover, the conductive PPy-coated layer could inhibit the obvious volume expansion like a firm armor and further avoid the pulverization of the active material and aggregation of generated products. Benefiting from the synergistic effects of the well-designed heterostructure and PPy-coated nanotube-like architecture, the prepared Mo3S4/CoMo2S4 heterostructure delivers high reversible capacity (1251.3 mAh g-1 at 300 mA g-1), superior rate performance (340.3 mAh g-1 at 5.0 A g-1) and excellent cycling lifespan (744.1 mAh g-1 after 600 cycles at a current density of 2.0 A g-1). Such a design concept provides a promising strategy towards heterostructure materials to enhance their lithium storage performances and boost their practical applications.

MRI Generated From CT for Acute Ischemic Stroke Combining Radiomics and Generative Adversarial Networks.

Compared to computed tomography (CT), magnetic resonance imaging (MRI) is more sensitive to acute ischemic stroke lesion. However, MRI is time-consuming, expensive, and susceptible to interference from metal implants. Generating MRI images from CT images can address the limitations of MRI. The key problem in the process is obtaining lesion information from CT. In this study, we propose a cross-modal image generation algorithm from CT to MRI for acute ischemic stroke by combining radiomics with generative adversarial networks. First, the lesion candidate region was obtained using radiomics, the radiomic features of the region were extracted, and the feature with the largest information gain was selected and visualized as a feature map. Then, the concatenation of the extracted feature map and the CT image was input in the generator. We added a residual module after the downsampling of the generator, following the general shape of U-Net, which can deepen the network without causing degradation problems. In addition, we introduced the lesion feature similarity loss function to focus the model on the similarity of the lesion. Through the subjective judgment of two experienced radiologists and using evaluation metrics, the results showed that the generated MRI images were very similar to the real MRI images. Moreover, the locations of the lesions were correct, and the shapes of lesions were similar to those of the real lesions, which can help doctors with timely diagnosis and treatment.

High-resolution intravascular magnetic resonance imaging of the coronary artery wall at 3.0 Tesla: toward evaluation of atherosclerotic plaque vulnerability.

BACKGROUND: To validate the feasibility of generating high-resolution intravascular 3.0 Tesla (T) magnetic resonance imaging of the coronary artery wall to further plaque imaging. METHODS: A receive-only 0.014-inch diameter magnetic resonance imaging guidewire (MRIG) was manufactured for intravascular imaging within a phantom experiment and the coronary artery wall of the swine. For coronary artery wall imaging, both high-resolution images and conventional resolution images were acquired. A 16-channel commercial surface coil for magnetic resonance imaging was employed for the control group. RESULTS: For the phantom experiment, the MRIG showed a higher signal-to-noise ratio than the surface coil. The peak signal-to-noise ratio of the MRIG and the surface coil-generated imaging were 213.6 and 19.8, respectively. The signal-to-noise ratio decreased rapidly as the distance from the MRIG increased. For the coronary artery wall experiment, the vessel wall imaging by the MRIG could be identified clearly, whereas the vessel wall imaging by the surface coil was blurred. The average signal-to-noise ratio of the artery wall was 21.1±5.40 by the MRIG compared to 8.4±2.19 by the surface coil, where the resolution was set at 0.2 mm × 0.2 mm × 2 mm. As expected, the high-resolution sequence clearly showed more details than the conventional resolution sequence set at 0.7 mm × 0.7 mm × 2.0 mm. Histological examination showed no evidence of mechanical injuries in the target vessel walls. CONCLUSIONS: The study validated the feasibility of generating magnetic resonance imaging (MRI) at 0.2 mm × 0.2 mm × 2 mm for the coronary artery wall using a 0.014 inch MRIG.

Separability of Acute Cerebral Infarction Lesions in CT Based Radiomics: Toward Artificial Intelligence-Assisted Diagnosis.

This study aims at analyzing the separability of acute cerebral infarction lesions which were invisible in CT. 38 patients, who were diagnosed with acute cerebral infarction and performed both CT and MRI, and 18 patients, who had no positive finding in either CT or MRI, were enrolled. Comparative studies were performed on lesion and symmetrical regions, normal brain and symmetrical regions, lesion, and normal brain regions. MRI was reconstructed and affine transformed to obtain accurate lesion position of CT. Radiomic features and information gain were introduced to capture efficient features. Finally, 10 classifiers were established with selected features to evaluate the effectiveness of analysis. 1301 radiomic features were extracted from candidate regions after registration. For lesion and their symmetrical regions, there were 280 features with information gain greater than 0.1 and 2 features with information gain greater than 0.3. The average classification accuracy was 0.6467, and the best classification accuracy was 0.7748. For normal brain and their symmetrical regions, there were 176 features with information gain greater than 0.1, 1 feature with information gain greater than 0.2. The average classification accuracy was 0.5414, and the best classification accuracy was 0.6782. For normal brain and lesions, there were 501 features with information gain greater than 0.1 and 1 feature with information gain greater than 0.5. The average classification accuracy was 0.7480, and the best classification accuracy was 0.8694. In conclusion, the study captured significant features correlated with acute cerebral infarction and confirmed the separability of acute lesions in CT, which established foundation for further artificial intelligence-assisted CT diagnosis.

Uniform Fe3O4/Gd2O3-DHCA nanocubes for dual-mode magnetic resonance imaging.

The multimodal magnetic resonance imaging (MRI) technique has been extensively studied over the past few years since it offers complementary information that can increase diagnostic accuracy. Simple methods to synthesize contrast agents are necessary for the development of multimodal MRI. Herein, uniformly distributed Fe3O4/Gd2O3 nanocubes for T 1-T 2 dual-mode MRI contrast agents were successfully designed and synthesized. In order to increase hydrophilicity and biocompatibility, the nanocubes were coated with nontoxic 3,4-dihydroxyhydrocinnamic acid (DHCA). The results show that iron (Fe) and gadolinium (Gd) were homogeneously distributed throughout the Fe3O4/Gd2O3-DHCA (FGDA) nanocubes. Relaxation time analysis was performed on the images obtained from the 3.0 T scanner. The results demonstrated that r 1 and r 2 maximum values were 67.57 ± 6.2 and 24.2 ± 1.46 mM-1·s-1, respectively. In vivo T 1- and T 2-weighted images showed that FGDA nanocubes act as a dual-mode contrast agent enhancing MRI quality. Overall, these experimental results suggest that the FGDA nanocubes are interesting tools that can be used to increase MRI quality, enabling accurate clinical diagnostics.

Saikosaponin D: A potential therapeutic drug for osteoarthritis.

Osteoarthritis is a degenerative joint disease. Currently, no effective therapeutic exists for osteoarthritis in the clinic setting. Inflammatory response and autophagy are key players in the occurrence and prognosis of osteoarthritis. In recent years, the regulation of inflammation and autophagy signal pathway has been touted as a potential treatment course for osteoarthritis. Saikosaponin D has anti-inflammatory and induces autophagy effects via inhibiting the nuclear transcription factor-κB, mTOR signaling pathways. Here in the report, we analyze and summarize recent evidences pertaining to the relationship between Saikosaponin and osteoarthritis. Published studies were scoured for in research databases, such as PubMed and Scopus with the keywords Saikosaponin and osteoarthritis. Phosphatidylinositol 3-kinase (PI3k)/Akt/mTOR signaling pathway is an important autophagy modulator, and can regulate chondrocytic autophagy, inflammation, and apoptosis. Saikosaponin D alleviates inflammation and regulates autophagy by inhibiting the PI3k/Akt/mTOR signaling pathway. Saikosaponin D could be a potential therapeutic drug for osteoarthritis.

The Inhibition of Inflammatory Signaling Pathway by Secretory Leukocyte Protease Inhibitor can Improve Spinal Cord Injury.

Spinal cord injury leads to loss of sensory motor functions below the damaged area, and can significantly affects physical and mental health. An effective spinal cord injury treatment is currently unavailable, in part, because of the intricacy of the brain, as well as the complex pathophysiological mechanism of the injury. Inflammation is an important biological process in multitudinous diseases, with no exception for spinal cord injury. Nuclear factor kappa beta (NF-κB) signaling pathway is a key inflammatory element, as it is involved in cell survival, apoptosis, proliferation, differentiation, and immune response. Activation of the NF-κB signaling pathway leads to the release of a large number of inflammatory factors that can affect tissue repair. Hence, the inhibition of inflammatory responses could improve the repair of injured spinal cord tissues. Secretory leukocyte protease inhibitor (SLPI) has anti-inflammatory and anti-bacterial properties, and promotes wound healing. SLPI can bind to the promoter region of tumor necrosis factor-αand interleukin-8 (IL-8) to inhibit the NF-κB signaling pathway. Additionally, SLPI can reduce secondary damages after spinal cord injury, and prevent further complications. In this report, we analyze the pathophysiological mechanism of spinal cord injury, the role of NF-κB signaling pathway following spinal cord injury, and how SLPI regulates the NF-κB signaling pathway to curtail inflammatory reaction.

Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium.

OBJECTIVE: To directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases. METHODS: After separation by adherent culture, VEC line supernatant, vascular endothelial growth factor (VEGF), bone morphogenetic protein-4 and hypoxia were used for the differentiation of VECs from DMSCs. The cell type was authenticated by flow cytometry, matrigel angiogenesis assay in vitro, and immunofluorescent staining during differentiation. The VEGF concentration was investigated by enzyme-linked immunosorbent assay. RESULTS: After 28 days of differentiation, the cell surface marker CD31 was significantly positive (80%-90%) by flow cytometry in the VEC line-conditioned culture, which was significantly higher than in the other groups. Differentiated DMSCs had the ability to ingest Dil-ac-LDL and vascularize in the conditioned culture, but not in the other groups. In the VEC line supernatant, the concentration of VEGF was very low. The VEGF concentration changed along with the differentiation into VECs in the medium of the conditioned culture group. CONCLUSION: VEC line supernatant can induce the differentiation of DMSCs into VECs, possibly through the pathway except VEGF.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats.

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire-mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy on esophageal squamous cell cancers. © RSNA, 2016.

Intrabiliary RF heat-enhanced local chemotherapy of a cholangiocarcinoma cell line: monitoring with dual-modality imaging--preclinical study.

PURPOSE: To determine whether magnetic resonance (MR) imaging heating guidewire-mediated radiofrequency (RF) hyperthermia could enhance the therapeutic effect of gemcitabine and 5-fluorouracil (5-FU) in a cholangiocarcinoma cell line and local deposit doses of chemotherapeutic drugs in swine common bile duct (CBD) walls. MATERIALS AND METHODS: The animal protocol was approved by the institutional animal care and use committee. Green fluorescent protein-labeled human cholangiocarcinoma cells and cholangiocarcinomas in 24 mice were treated with (a) combination therapy with chemotherapy (gemcitabine and 5-FU) plus RF hyperthermia, (b) chemotherapy only, (c) RF hyperthermia only, or (d) phosphate-buffered saline. Cell proliferation was quantified, and tumor changes over time were monitored with 14.0-T MR imaging and optical imaging. To enable further validation of technical feasibility, intrabiliary local delivery of gemcitabine and 5-FU was performed by using a microporous balloon with (eight pigs) or without (eight pigs) RF hyperthermia. Chemotherapy deposit doses in the bile duct walls were quantified by means of high-pressure liquid chromatography. The nonparametric Mann-Whitney U test and the paired-sample Wilcoxon signed rank test were used for data analysis. RESULTS: Combination therapy induced lower mean levels of cell proliferation than chemotherapy only and RF hyperthermia only (0.39 ± 0.13 [standard deviation] vs 0.87 ± 0.10 and 1.03 ± 0.13, P < .001). Combination therapy resulted in smaller relative tumor volume than chemotherapy only and RF hyperthermia only (0.65 ± 0.03 vs 1.30 ± 0.021 and 1.37 ± 0.05, P = .001). Only in the combination therapy group did both MR imaging and optical imaging show substantial decreases in apparent diffusion coefficients and fluorescent signals in tumor masses immediately after the treatments. Chemotherapy quantification showed a higher average drug deposit dose in swine CBD walls with intrabiliary RF hyperthermia than without it (gemcitabine: 0.32 mg/g of tissue ± 0.033 vs 0.260 mg/g ± 0.030 and 5-FU: 0.660 mg/g ± 0.060 vs 0.52 mg/g ± 0.050, P < .05). CONCLUSION: The use of intrabiliary MR imaging heating guidewire-mediated RF hyperthermia can enhance the chemotherapeutic effect on a human cholangiocarcinoma cell line and local drug deposition in swine CBD tissues.

Formation of thermo-sensitive polyelectrolyte complex micelles from two biocompatible graft copolymers for drug delivery.

Thermo-sensitive polyelectrolyte complex (PEC) micelles assembled from two biocompatible graft copolymers chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAM) and carboxymethyl cellulose-g-poly(N-isopropylacrylamide) (CMC-g-PNIPAM) were prepared for delivery of 5-fluorouracil (5-FU). The PEC micelles showed a narrow size distribution with core-shell structure, in which the core formed from positively charged CS and negatively charged CMC by electrostatic interactions and the shell formed from thermo-sensitive PNIPAM. The synthesized PEC micelles have lower critical solution temperatures (LCST) in the region of 37°C, which is favorable for smart drug delivery applications. The hydrogen bondings between PEC micelles and 5-FU increased the drug loading. Changing temperature, pH or ionic strength, a sustained and controlled release was observed due to the deformation of PEC micelles. Adding glutaraldehyde, a chemical crosslinking reagent, was an efficient way to reinforce the micelles structure and decrease the initial burst release. Cytotoxicity assays showed that drug-loaded PEC micelles retained higher cell inhibition efficiency in HeLa cells.

Diffusion-weighted MRI monitoring of pancreatic cancer response to radiofrequency heat-enhanced intratumor chemotherapy.

The aim of this study was to evaluate the feasibility of using diffusion-weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)-enhanced chemotherapy. Human pancreatic carcinoma cells (PANC-1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate-buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion-weighted MRI and T2 -weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14-T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy-only, RFH-only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH-enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH-integrated local chemotherapy.