Magnetic liquid metal loaded nano-in-micro spheres as fully flexible theranostic agents for SMART embolization.

Transcatheter arterial chemoembolization (TACE) has become one of the preferred choices for advanced liver cancer patients. Current clinically used microsphere embolic agents, such as PVA, gelatin, and alginate microspheres, have limited therapeutic efficacy and lack the function of real-time imaging. In this work, we fabricated magnetic liquid metal nanoparticle (Fe@EGaIn NP) loaded calcium alginate (CA) microspheres (denoted as Fe@EGaIn/CA microspheres), which integrate CT/MR dual-modality imaging and photothermal/photodynamic functions of the Fe@EGaIn NP core, as well as embolization and drug-loading functions of CA microspheres. Namely, such nano-in-micro spheres can be used as fully flexible theranostic agents to achieve smart-chemoembolization. It has been confirmed by in vitro and in vivo experiments that Fe@EGaIn/CA microspheres have advantageous morphology, favorable biocompatibility, splendid versatility, and advanced embolic efficacy. Benefiting from these properties, excellent therapeutic efficiency was achieved with a tumor growth-inhibiting value of 100% in tumor-bearing rabbits. As a novel microsphere embolic agent with promising therapeutic efficacy and diagnostic capability, Fe@EGaIn/CA microspheres have shown potential applications in clinical transcatheter arterial chemoembolization. And the preparation strategy presented here provides a generalized paradigm for achieving multifunctional and fully flexible theranostics.

A novel multimodal nanoplatform for targeting tumor necrosis.

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Delivery of Arsenic Trioxide by Multifunction Nanoparticles To Improve the Treatment of Hepatocellular Carcinoma.

Arsenic trioxide (ATO) is effective in the treatment of hematological malignancies and solid tumors. However, its toxicity and side effects are severe, posing an obstacle in its clinical application. A controlled-release ATO carrier with mitochondrial targeting was constructed in this study. The safety and efficacy in vitro were investigated using a hemolysis test, cytotoxicity, proliferation, migration, apoptosis, and other changes in cell behavior. The safety and efficacy were further evaluated in vivo by hematoxylin-eosin staining, terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling staining, and blood testing in tumor-bearing mice. Immunohistochemically and western blotting experiments were conducted to explore the mechanism of combination therapy of material-based chemotherapy and microwave hyperthermia in vitro. We demonstrated that the nano-zirconia (ZrO2) loading platform may be used to administer the ATO, with local precision-controlled release and mitochondrial targeting. Furthermore, we showed the safety of this approach for delivering high doses of ATO. In addition, we explored this new method in combination with in vitro microwave heat therapy, providing a potentially novel intravenous approach to chemotherapy. We described a new non-invasive treatment that improved the efficacy of ATO chemotherapy against hepatocellular carcinoma through nano-ZrO2 carriers.

Mitochondria-targeting nanoparticles for enhanced microwave ablation of cancer.

Although microwave ablation is widely used in the treatment of hepatocellular carcinoma, it is only recommended for the therapy of cancer with a diameter of 3 cm or less because of the limited heat transmission radius. Mitochondria play an important role in the apoptotic events of tumor cells. Here, we developed mitochondria-targeting zirconia (ZrO2) complex nanoparticles (MZCNs) as nanoagents for efficient cancer therapy by microwave ablation. The MZCNs are composed of ZrO2 nanoparticles encapsulating the microwave-sensitive ionic liquid (IL) and co-decorated with the mitochondria-targeting molecule of triphenylphosphonium (TPP), and the tumor cell-targeting peptide iRGD. The cell experiment results reveal that the amount of MZCNs accumulated in the tumor is obviously increased by the synergistically targeted delivery of TPP and iRGD peptide after administration by intravenous injection. Besides, the in vitro experiments demonstrate that MZCNs are distributed preferentially in the mitochondria with the assistance of TPP molecules. More importantly, the in vivo experiments in mice administered with MZCNs show that the effective area with a temperature above 42 °C was about 2.8-fold larger than that of the controls due to the targeting effect and better microwave sensitivity of the MZCNs. As such, the cancer in mice can be eradicated without recurrence, demonstrating the MZCNs as promising nanoagents for efficient cancer therapy by microwave ablation.

Real-time Monitoring of Nanoparticle-based Therapeutics: A Review.

BACKGROUND: With the development of nanomaterials, nanoparticle-based therapeutics have found increasing application in various fields, including clinical and basic medicine. Real-time monitoring of nanoparticle-based therapeutics is considered critical to both pharmacology and pharmacokinetics. METHODS: In this review, we discuss the different methods of real-time monitoring of nanoparticle-based therapeutics comprising different types of nanoparticle carriers, such as metal nanoparticles, inorganic nonmetallic nanoparticles, biodegradable polymer nanoparticles, and biological nanoparticles. RESULTS: In the light of examples and analyses, we conclude that the methods of analysis of the four types of nanoparticle carriers are commonly used methods and mostly not necessary. Under most circumstances, real-time monitoring differs according to nanoparticle type, drugs, diseases, and surroundings. CONCLUSION: With technology development and advanced researches, there have been increasing measures to track the real-time changes in nanoparticles, and this has led to great progress in pharmacology and therapeutics. However, future studies are warranted to determine the accuracy, applicability, and practicability of different technologies.

Statins and the risk of cirrhosis in hepatitis B or C patients: a systematic review and dose-response meta-analysis of observational studies.

Hepatitis B and hepatitis C are leading causes of chronic liver disease, particularly cirrhosis. Recently, several studies have observed that statins have an inverse relationship with cirrhosis in hepatitis B or C patients. However, no published meta-analysis studied the protective effect of statins on cirrhosis. Thus, we conducted a systematic review and meta-analysis of published observational studies to better understand the relationship between statins and the risk of cirrhosis. Relevant studies were identified by searching PubMed, EMBASE, and ISI Web of Science for articles published before April 2017. The Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. Six cohort studies, including 38951 cases of cirrhosis in 263573 patients with hepatitis B or C, were identified to investigate the relationship between statins and the risk of cirrhosis. The Newcastle-Ottawa Scale scores for the included studies ranged from 6 to 9, with four high-quality studies and only two of medium quality. The use of statins was associated with a significant 42% reduction in the risk of cirrhosis, without obvious heterogeneity. In addition, this protective effect was more obvious in Asian countries. Moreover, dose-response analysis suggested each additional 50 cumulative defined daily doses (cDDD) of statins decreases the risk of cirrhosis by 11% (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.86-0.93, p = 0.001). In summary, statin use is associated with a decreased incidence rate of cirrhosis and is most pronounced in Eastern countries but also in Western countries.