Drug-Eluting Bead Transarterial Chemoembolization Versus Radiofrequency Ablation as an Initial Treatment of Single Small (≤ 3 cm) Hepatocellular Carcinoma.

BACKGROUND: In this study, we aimed to compare the long-term therapeutic outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) with those of radiofrequency ablation (RFA) for the initial treatment of a single small (≤ 3 cm) hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2021, 259 consecutive patients who underwent DEB-TACE (67 patients) or RFA (192 patients) as a first-line treatment for a single small HCC were enrolled in this retrospective study. The therapeutic outcomes, including cumulative intrahepatic local tumor progression (LTP), progression-free survival (PFS), and long-term overall survival (OS) rates, were compared between the two groups before and after propensity score (PS) matching. Multivariate Cox proportional hazard models were used to evaluate the prognostic factors and differences in OS and PFS between the two groups for all 92 patients after PS matching. RESULTS: After PS matching, the 1-, 2-, 3-, and 5-year LTP rates were lower in the RFA group than those in the DEB-TACE group (P < 0.001), and the 1-, 2-, 3-, and 5-year PFS rates in the RFA group were higher than those in the DEB-TACE group (P = 0.007). However, the 1-, 2-, 3-, and 5-year OS rates were not significantly different between the RFA and DEB-TACE groups (P = 0.584). Moreover, the OS was not significantly different between the RFA and DEB-TACE groups in the univariate and multivariate analyses, with a hazard ratio (HR) of 0.81. The PFS was significantly higher in the RFA group than that in the DEB-TACE group in the univariate analyses, with a HR of 0.44 (P = 0.009). Multivariate Cox regression analysis showed that albumin (P = 0.019) was an independent prognostic factor for OS. Additionally, the major complication rates were not significantly different between the DEB-TACE and RFA groups (P = 1.000). CONCLUSION: The LTP and PFS rates of RFA were superior to those of DEB-TACE in the initial treatment of single small HCC after PS matching. However, the OS rates were not significantly different between RFA and DEB-TACE. Therefore, DEB-TACE may be considered an efficient substitute for RFA in some patients with a single small HCC who are ineligible for RFA.

Four-dimensional flow MR imaging for evaluating treatment response after transcatheter arterial chemoembolization in cirrhotic patients with hepatocellular carcinoma.

PURPOSE: To prospectively evaluate the potential of four-dimensional (4D) flow magnetic resonance imaging (MRI) in predicting treatment responses after transcatheter arterial chemoembolization (TACE) in cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: A total of 195 patients were classified into four groups (A-D): A, cirrhotic patients without HCC (n = 30); B, cirrhotic patients with HCC before TACE (n = 75); C, cirrhotic patients with HCC showing an incomplete response following TACE (n = 56); and D, cirrhotic patients with HCC achieving a complete response (CR) following TACE (n = 34). The patients were subjected to routine laboratory tests and 4D flow MRI using a 3-T MRI system to measure the quantitative parameters of blood flow in the portal vein (PV), splenic vein (SV), and superior mesenteric vein. The data collected by 4D flow MRI were compared among the groups using one-way analysis of variance. A multivariate analysis was performed to verify the association of clinical characteristics and 4D flow parameters with CR after TACE treatment. RESULTS: The average through-plane velocity, peak velocity magnitude, average net flow, peak flow, and net forward volume in the PV and SV were significantly lower in groups B and C (P < 0.05) compared to those in group A. Moreover, average through-plane velocity and peak velocity magnitude in the PV in groups B and C were significantly lower than those in group D (P < 0.05). The multivariate analysis demonstrated that the average through-plane velocity and peak velocity magnitude in the PV were independently associated with CR in HCC patients after TACE (P < 0.05). CONCLUSION: The quantitative flow data obtained by 4D flow MRI may be useful for predicting CR after TACE in cirrhotic patients with HCC.

Periumbilical Transverse Incision for Reducing Incisional Hernia in Laparoscopic Colon Cancer Surgery.

BACKGROUND: Although off-midline incisions (unilateral low transverse or Pfannenstiel incision) have been reported to have a lower incidence of incisional hernia (IH) than periumbilical vertical incision for the purpose of specimen extraction, it is most commonly used in laparoscopic colon cancer surgery because off-midline incisions are associated with the limitation of colon exteriorization. This study aims to investigate the risk of IH after laparoscopic colectomy and compare midline vertical incision versus transverse incision focusing on the incidence of IH. METHODS: Patients who underwent elective laparoscopic colectomy due to colon malignancy from June 2015 to May 2017 were included. All patients had either vertical (n = 429) or muscle splitting periumbilical transverse incisions (n = 125). RESULTS: Median duration of the follow-up period was 23.6 months, during which IHs occurred in 12.1% patients. The incidence of hernia was significantly lower in the transverse group (3 vs. 64, 2.4% vs. 14.9%, p < 0.001). On multivariate analysis, BMI ≥ 23 [odds ratio (OR) 2.282, 95% confidence interval (CI) 1.245-4.182, p = 0.008], postoperative surgical site infection (OR 3.780, 95% CI 1.969-7.254, p < 0.001) and vertical incision (OR 7.113, 95% CI 2.173-23.287, p < 0.001) were independently related with increased incidence of IH. CONCLUSIONS: A muscle splitting periumbilical transverse incision could significantly reduce the rate of IH in minimally invasive colon cancer surgery.

Stimuli-Responsive Polymeric Nanomaterials for the Delivery of Immunotherapy Moieties: Antigens, Adjuvants and Agonists.

Immunotherapy has been investigated for decades, and it has provided promising results in preclinical studies. The most important issue that hinders researchers from advancing to clinical studies is the delivery system for immunotherapy agents, such as antigens, adjuvants and agonists, and the activation of these agents at the tumour site. Polymers are among the most versatile materials for a variety of treatments and diagnostics, and some polymers are reactive to either endogenous or exogenous stimuli. Utilizing this advantage, researchers have been developing novel and effective polymeric nanomaterials that can deliver immunotherapeutic moieties. In this review, we summarized recent works on stimuli-responsive polymeric nanomaterials that deliver antigens, adjuvants and agonists to tumours for immunotherapy purposes.

The Anti-Inflammatory Role of Bilirubin on "Two-Hit" Sepsis Animal Model.

INTRODUCTION: Bilirubin is a product of the heme catabolism pathway, and it is excreted in bile and removed from the body through the urine. Bilirubin has potent antioxidant properties but also plays a role in anti-inflammation by protecting the body against endotoxin-induced lung inflammation, down-regulating the expression of adhesion molecules, and inhibiting the infiltration of inflammatory cells. Thus, bilirubin is a promising agent that could use in inflammation disease treatment. The application of bilirubin on the "two-hit" sepsis animal model has been, to date, unknown. METHODS: we used lipopolysaccharide to induce initial insults in C57BL/6 mice. After 24 h, mice underwent cecal ligation and puncture to induce the "two-hit" sepsis model. Next, mice were administered 30 mg/kg bilirubin and we observed an improvement. RESULTS: We observed that bilirubin inhibited the expression of pro-inflammatory cytokines, while the levels of anti-inflammatory cytokines were significantly augmented in the lung. Bilirubin improved the survival rate in the sepsis model. Furthermore, we suggest that bilirubin can modulate the accumulation of T-regulatory cells and myeloid-derived suppressor cells. Notably, bilirubin suppressed the activation and functions of T-cells. CONCLUSIONS: These results clarified that bilirubin might improve tissue injury in sepsis through anti-inflammatory mechanisms.

Intravitreal Injection of Liposomes Loaded with a Histone Deacetylase Inhibitor Promotes Retinal Ganglion Cell Survival in a Mouse Model of Optic Nerve Crush.

Various neuroprotective agents have been studied for the treatment of retinal ganglion cell (RGC) diseases, but issues concerning the side effects of systemically administered drugs and the short retention time of intravitreally injected drugs limit their clinical applications. The current study aimed to evaluate the neuroprotective effects of intravitreally injected trichostatin A (TSA)-loaded liposomes in a mouse model of optic nerve crush (ONC) and determine whether TSA-loaded liposomes have therapeutic potential in RGC diseases. The histone deacetylase inhibitor, TSA, was incorporated into polyethylene glycolylated liposomes. C57BL/6J mice were treated with an intravitreal injection of TSA-loaded liposomes and liposomes loaded with a lipophilic fluorescent dye for tracking, immediately after ONC injury. The expression of macroglial and microglial cell markers (glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1), RGC survival, and apoptosis were assessed. We found that the liposomes reached the inner retina. Their fluorescence was detected for up to 10 days after the intravitreal injection, with peak intensity at 3 days postinjection. Intravitreally administered TSA-loaded liposomes significantly decreased reactive gliosis and RGC apoptosis and increased RGC survival in a mouse model of ONC. Our results suggest that TSA-loaded liposomes may help in the treatment of various RGC diseases.

Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells.

Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (Mn3O4) and hematite (Fe3O4) nanoparticle (GMF). The highly stable HART nanoassembly has enhanced CD44-mediated intracellular uptake along with hyaluronidase (hylase) and redox-responsive drug-gene release. With Bcl-2 gene silencing induced by the successful delivery of HART in multidrug-resistant MCF7 breast cancer cells, the synergistic cytotoxic effect of Bcl-2 silencing and DOX was achieved. In addition, the HART nanoassembly containing GMF exhibited excellent dual MRI contrast (T1/T2) by reducing artifact signals. Overall, the HART nanoassembly with its enhanced theranostic properties has the potential to improve the therapeutic efficacy in future preclinical and clinical trials.

Bioactive Nanoparticles for Cancer Immunotherapy.

Currently, immunotherapy is considered to be one of the effective treatment modalities for cancer. All the developments and discoveries in this field up to the recent Nobel Prize add to the interest for research into this vast area of study. Targeting tumor environment as well as the immune system is a suitable strategy to be applied for cancer treatment. Usage of nanoparticle systems for delivery of immunotherapeutic agents to the body being widely studied and found to be a promising area of research to be considered and investigated further. Nanoparticles for immunotherapy would be one of the effective treatment options for cancer therapy in the future due to their high specificity, efficacy, ability to diagnose, imaging, and therapeutic effect. Among the many nanoparticle systems, polylactic-co-glycolic acid (PLGA) nanoparticles, liposomes, micelles, gold nanoparticles, iron oxide, dendrimers, and artificial exosomes are widely used for immunotherapy of cancer. Moreover, the combination therapy found to be the more effective way of treating the tumor. Here, we review the current trends in nanoparticle therapy and efficiency of these nanosystems in delivering antigens, adjuvants, therapeutic drugs, and other immunotherapeutic agents. This review summarizes the currently available bioactive nanoparticle systems for cancer immunotherapy.

Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time.

PURPOSE: To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using 1 H-MRS (proton magnetic resonance spectroscopy) with long echo time and to test the reproducibility of human study in an animal model. Liver biopsy is the gold standard for diagnosing NAFLD but with practical constraints. 1 H-MRS allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease. MATERIALS AND METHODS: In all, 32 subjects (11 patients with nonalcoholic steatohepatitis [NASH], 15 with simple steatosis [SS], and six healthy controls) were studied. For test reproducibility, 36 C57BL/6 mice, including 10 mice with streptozotocin-induced NASH, 15 with SS, and 11 high-fat diet controls, were studied. 1 H-MRS measurements at 3T and 4.7T MRI were performed on a localized voxel of the liver using PRESS sequence. Hepatic alanine (Ala), lactate+triglyceride (Lac+TG), and TG levels were compared between NASH, SS, and control groups using analysis of variance (ANOVA) tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolite levels and pathologic grades or NAFLD activity scores (NAS) were assessed using Pearson's correlation. RESULTS: NASH patients had higher levels of Ala (P < 0.001), Lac+TG (P < 0.001), and TG (P < 0.05) than SS patients or controls. The AUROC curve to distinguish NASH from SS was 1.00 (95% confidence interval [CI] 1.00-1.00) for Ala and 0.782 (95% CI 0.61-0.96) for Lac+TG. Ala and Lac+TG concentrations were positively correlated with steatosis grade (Ala Pearson's r = 0.723; Lac+TG r = 0.446), lobular inflammation (Ala r = 0.513), and NAS (Ala r = 0.743; Lac+TG r = 0.474). CONCLUSION: 1 H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310.

Combined Therapy of Transcatheter Arterial Chemoembolization and Radiofrequency Ablation versus Surgical Resection for Single 2-3 cm Hepatocellular Carcinoma: A Propensity-Score Matching Analysis.

PURPOSE: To compare therapeutic outcomes of radiofrequency (RF) ablation combined with transcatheter arterial chemoembolization vs surgical resection (SR) for single 2-3 cm hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy patients underwent combined chemoembolization/RF ablation therapy and 84 underwent SR. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), disease-free survival (DFS), and overall survival (OS) rates, as well as major complications and duration of hospital stay, were compared between groups before and after propensity-score matching. RESULTS: LTP and IDR had developed in 9 (12.9%) and 24 (34.3%) patients in the combined treatment group and in 7 (8.3%) and 24 (28.6%) patients in the SR group (P = .262 and P = .252, respectively). The 1-, 3-, 4-, and 5-year DFS rates were similar between groups (82.6%, 53.2%, 53.2%, and 37.6%, respectively, vs 84.5%, 63.6%, 59.2%, and 52.1%, respectively; P = .278), and 1-, 3-, 4-, and 5-year OS rates were also comparable (94.2%, 81.2%, 74.1%, and 59.4%, respectively, vs 95.2%, 86.3%, 84.0%, and 80.3%, respectively; P = .081). After matching (n = 98), LTP, IDR, DFS, and OS rates were still similar (P = .725, P = .826, P = .484, and P = .578, respectively). Major complication rate was not significantly different (2.9% vs. 6.0%; P = .596); however, after matching, major complication rate was higher in SR group (2.0% vs. 6.1%; P < .001). Hospital stays were significantly longer in the SR group (16.6 ± 6.7 d vs 8.5 ± 4.1 d; P < .001). CONCLUSIONS: Before and after matching, there were no significant differences in long-term therapeutic outcomes between combined chemoembolization/RF ablation and SR groups. Therefore, combined chemoembolization/RF ablation therapy may be an alternative treatment for single 2-3 cm HCCs.

Pre-treatment estimation of future remnant liver function using gadoxetic acid MRI in patients with HCC.

BACKGROUND & AIMS: This study aimed to determine whether the predicted remnant liver function on dynamic hepatocyte-specific contrast media-enhanced magnetic resonance (DHCE-MR) imaging correlates with the results of the indocyanin green retention test (ICG R15) after hepatic resection or radiofrequency ablation (RFA). METHODS: This prospective multicenter study was approved by the Institutional Review Boards of each hospital. Informed consents were obtained from all. DHCE-MRI and ICG R15 were performed in 57 patients scheduled to undergo hepatectomy or RFA for hepatocellular carcinoma, once before treatment and repeated on post-treatment day 3. In nine donors and three recipients, DHCE-MRI and ICG R15 were performed only preoperatively. The predicted remnant liver function (HEFml) was estimated using the hepatic extraction fraction (HEF) multiplied by the remnant liver volume, and compared with post-treatment ICG R15. Intra-individual heterogeneity of HEF was assessed using pooled coefficients of variation (CV) among hepatic segments. Finally, development of post-treatment hepatic failure was assessed according to the 50-50 criteria on post-treatment day 5. RESULTS: Predicted remnant HEFml showed a negative correlation with post-treatment ICG R15 (r=-0.45, p=0.001), whereas liver volume did not (p>0.05). There were significant correlations between pre-treatment HEFml and pre-treatment ICG R15 (r=-0.33, p=0.006) and between post-treatment HEFml and post-treatment ICG R15 (r=-0.54, p<0.001). Pooled CV among segmental HEFs was 12.6%. No patients showed post-treatment liver failure on post-treatment day 5. CONCLUSIONS: DHCE-MRI using Gd-EOB-DTPA was able to provide both global and segmental liver function information, and post-treatment remnant liver function predicted on pre-treatment DHCE-MRI showed a significant negative correlation with post-treatment ICG R15. LAY SUMMARY: Post-treatment liver function could be predicted at pre-treatment DHCE-MRI. Liver function was heterogeneous among the liver segments. Liver anatomy, disease extent, and underlying liver function can be assessed in one DHCE-MRI examination. CLINICAL TRIAL NUMBER: ClinicalTrials.gov number, NCT01490203.

Targeted antitumor efficacy and imaging via multifunctional nano-carrier conjugated with anti-HER2 trastuzumab.

In this study, we prepared iron oxide nanoparticle and doxorubicin-loaded multifunctional nano-carrier (IONP/DOX-MFNC), capable of simultaneous cancer targeting via a herceptin monoclonal antibody, controlled anticancer drug delivery, as well as imaging modalities of magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging. IONP and DOX were efficiently loaded into the nano-carrier, and a desirable pH-responsive release of DOX was achieved by MFNC. The nano-carrier showed much higher cellular uptake and stronger cytotoxicity to HER2 overexpressed SK-BR-3 (human breast cancer cells) than MCF-7, a negative control cell, suggesting specific cancer targeting via HER2 receptor. In an in vivo tumor xenograft model, IONP/DOX-MFNC showed higher tumor uptake and significantly enhanced tumor regression than the nano-carrier without the antibody. Thus, DOX-loaded, multi-functional nano-carrier with HER2 antibody was effective for both imaging and therapy, showing the potential for early stage cancer diagnosis and simultaneous therapy. FROM THE CLINICAL EDITOR: In this study, efficacy -both for imaging and treatment - was demonstrated on a doxorubicin and iron oxide nanoparticle loaded multifunctional nano-carrier with HER2 antibody to show the potential for early stage cancer diagnosis and simultaneous therapy.

Biomedical Applications of Magnetically Functionalized Organic/Inorganic Hybrid Nanofibers.

Nanofibers are one-dimensional nanomaterial in fiber form with diameter less than 1 µm and an aspect ratio (length/diameter) larger than 100:1. Among the different types of nanoparticle-loaded nanofiber systems, nanofibers loaded with magnetic nanoparticles have gained much attention from biomedical scientists due to a synergistic effect obtained from the unique properties of both the nanofibers and magnetic nanoparticles. These magnetic nanoparticle-encapsulated or -embedded nanofiber systems can be used not only for imaging purposes but also for therapy. In this review, we focused on recent advances in nanofibers loaded with magnetic nanoparticles, their biomedical applications, and future trends in the application of these nanofibers.

Imaging of actinomycosis in various organs: a comprehensive review.

Actinomycosis is a chronic suppurative bacterial infection caused by Actinomyces species. Actinomyces israelii is the organism most commonly found in human disease. Actinomycosis usually manifests with abscess formation, dense fibrosis, and draining sinuses. The disease is further characterized by the tendency to extensively spread beyond normal fascial and connective tissue planes. Actinomycosis occurs most commonly in the cervicofacial region (50%-65%), followed by the thoracic (15%-30%) and abdominopelvic (20%) regions, but rarely involves the central nervous system. Most cases of cervicofacial actinomycosis are odontogenic in origin. In the acute form, cervicofacial disease can manifest with soft-tissue swelling, a painful pyogenic abscess, or a mass lesion. In the subacute to chronic form, a painless indurated mass can spread to the skin, leading to draining sinus tracts. Thoracic manifestations include parenchymal, bronchiectatic, and endobronchial actinomycosis. At computed tomography, pulmonary actinomycosis usually appears as chronic segmental airspace consolidation containing necrotic low-attenuation areas with peripheral enhancement. Abdominopelvic actinomycosis preferentially involves the ileocecal region, ovary, and fallopian tube. The imaging findings favoring abdominopelvic actinomycosis include strong enhancement in the solid portion of the mass after contrast material administration, small rim-enhancing abscesses within the mass, and extensive inflammatory extensions. Actinomycosis in the central nervous system may produce brain abscess, meningitis, subdural empyema, actinomycetoma, and spinal and cranial epidural abscess. In general, actinomycosis responds well to antibiotic therapy, but long-term follow-up after treatment is needed because of frequent relapses.

Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents.

Treatment of Ischemic Stroke by Atorvastatin-Loaded PEGylated Liposome.

There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia-reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood-brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.

Magnet-Guided Temozolomide and Ferucarbotran Loaded Nanoparticles to Enhance Therapeutic Efficacy in Glioma Model.

Background. The aim of the study was to synthesize liposomal nanoparticles loaded with temozolomide and ferucarbotran (LTF) and to evaluate the theranostic effect of LTF in the glioma model. Methods. We synthesized an LTF that could pass through the Blood Brain Barrier (BBB) and localize in brain tumor tissue with the help of magnet guidance. We examined the chemical characteristics. Cellular uptake and cytotoxicity studies were conducted in vitro. A biodistribution and tumor inhibition study was conduted using an in vivo glioma model. Results. The particle size and surface charge of LTF show 108 nm and -38 mV, respectively. Additionally, the presence of ferucarbotran significantly increased the contrast agent effect of glioma compared to the control group in MR imaging. Magnet-guided LTF significantly reduced the tumor size compared to control and other groups. Furthermore, compared to the control group, our results demonstrate a significant inhibition in brain tumor size and an increase in lifespan. Conclusions. These findings suggest that the LTF with magnetic guidance represents a novel approach to address current obstacles, such as BBB penetration of nanoparticles and drug resistance. Magnet-guided LTF is able to enhance therapeutic efficacy in mouse brain glioma.

Surface tunable polymersomes loaded with magnetic contrast agent and drug for image guided cancer therapy.

Polymersomes with different surface charges were synthesized from polysuccinimide (p) by introducing positively charged polyethylenimine (PEI-P), neutrally charged polyethylene glycol (PEG-P), and negatively charged glycine (GLY-P) to the polymer backbone polysuccinimide (P). Then, the polymersomes were prepared with super paramagnetic iron nanoparticles (SPIONs) to obtain PEI-P encapsulating SPIONs (PEI-PS), PEG-P encapsulating SPIONs (PEG-PS), and GLY-P encapsulating SPIONs (GLY-PS), respectively. The average particle sizes of GLY-PS, PEG-PS, and PEI-PS were analyzed by dynamic light scattering, and it was around 163.nm, 105 nm, and 285 nm, respectively. The surface charges of GLY-PS, PEG-PS, and PEI-PS was found to be -29.5, -18.9, and +44, respectively. The presence of PEI, PEG, and GLY in the polymer backbone was confirmed with nuclear magnetic resonance (NMR). The GLY-PS, PEG-PS, and PEI-PS were loaded with the anticancer drug paclitaxel during the preparation. The drug release from the PEG-PS was faster compared to GLY-PS and PEI-PS. An in vivo hemi-spleen mouse metastatic liver model was established and imaged with MRI after intravenous administration of GLY-PS, PEG-PS, and PEI-PS. From the T2-weighted imaging, it was evident that PEG-PS accumulated in the spleen and liver more efficiently than the other charged formulations of GLY-PS and PEI-PS. From this study, the nanoparticle-based delivery and imaging of anti-cancer drugs could be effectively demonstrated simultaneously.