B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC.

BACKGROUND: The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). RESULTS: In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. CONCLUSION: This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma.

Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal therapy (PTT) has many outstanding properties, but suffers from poor photostability of photosensitizer and incomplete ablation. Multimodal therapies could combine the advantages of different therapy methods to improve antitumor efficiency. Hence, we designed a nano-delivery system (ICG&DHA@ZIF-8) using zeolitic imidazolate framework-8 (ZIF-8) with a high porous rate and pH sensitivity property, to co-load DHA and indocyanine green (ICG). Dynamic light scattering and transmission electron microscopy were used to characterize the prepared nanoparticles. The photothermal conversion and drug release performances of ICG&DHA@ZIF-8 were investigated. In vitro antitumor efficacy and cellular uptake were studied. The mechanism of the combination treatment was studied by reactive oxygen species level detection and western blot assays. In vivo antitumor assays were then studied with the guidance of ex vivo imaging. The results showed that the ICG&DHA@ZIF-8 based combination therapy could efficiently kill hepatic carcinoma cells and suppress tumor growth. This research provides a potential nanodrug for the treatment of hepatic carcinoma.

Strong Near-Infrared Absorbing and Biocompatible CuS Nanoparticles for Rapid and Efficient Photothermal Ablation of Gram-Positive and -Negative Bacteria.

Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common infectious bacteria in our daily life, and seriously affect human's health. Because of the frequent and extensive use of antibiotics, the microbial strains forming drug resistance have become more and more difficult to deal with. Herein, we utilized bovine serum albumin (BSA) as the template to synthesize uniform copper sulfide (CuS) nanoparticles via a biomineralization method. The as-prepared BSA-CuS nanocomposites showed good biocompatibility and strong near-infrared absorbance performance and can be used as an efficient photothermal conversion agent for pathogenic bacteria ablation with a 980 nm laser at a low power density of 1.59 W/cm2. The cytotoxicity of BSA-CuS nanocomposite was investigated using skin fibroblast cells and displayed good biocompatibility. Furthermore, the antibacterial tests indicated that BSA-CuS nanocomposite showed no antibacterial activity without NIR irradiation. In contrast, they demonstrated satisfying killing bacterial ability in the presence of NIR irradiation. Interestingly, S. aureus and E. coli showed various antibacterial mechanisms, possibly because of the different architectures of bacterial walls. Considering the low cost, easy preparation, excellent biocompatibility and strong photothermal convention efficiency (24.68%), the BSA-CuS nanocomposites combined with NIR irradiation will shed bright light on the treatment of antibiotic-resistant pathogenic bacteria.

Meditation and blood pressure: a meta-analysis of randomized clinical trials.

OBJECTIVES: We meta-analyzed the effect of meditation on blood pressure (BP), including both transcendental meditation and non-transcendental meditation interventions. METHODS: We identified randomized controlled trials (RCTs) that examined the BP responses to meditation interventions through a systematic literature search of the PubMed, ABI/INFORM, MEDLINE, EMBASE, PsycINFO, and CINAHL databases (from January 1980 to October 2015). We meta-analyzed the change in SBP and DBP, stratified by type of meditation (transcendental meditation vs. non-transcendental meditation intervention) and by type of BP measurement [ambulatory BP monitoring (ABPM) vs. non-ABPM measurement]. RESULTS: Nineteen studies met the eligibility criteria. Among the studies using the ABPM measurement, the pooled SBP effect estimate was -2.49 mmHg [95% confidence interval (CI): -7.51, 2.53] for transcendental meditation intervention (statistically insignificant) and -3.77 mmHg (95% CI: -5.33, -2.21) for non-transcendental meditation interventions, whereas the pooled DBP effect estimate was -4.26 mmHg (95% CI: -6.21, -2.31) for transcendental meditation interventions and -2.18 mmHg (95% CI: -4.28, -0.09) for non-transcendental meditation interventions. Among the studies using the non-ABPM measurement, the pooled SBP effect estimate from transcendental meditation interventions was -5.57 mmHg (95% CI: -7.41, -3.73) and was -5.09 mmHg with non-transcendental meditation intervention (95% CI: -6.34, -3.85), whereas the pooled effect size in DBP change for transcendental meditation interventions was -2.86 mmHg (95% CI: -4.27, -1.44) and was -2.57 mmHg (95% CI: -3.36, -1.79) for non-transcendental meditation interventions. CONCLUSION: Non-transcendental meditation may serve as a promising alternative approach for lowering both SBP and DBP. More ABPM-measured transcendental meditation interventions might be needed to examine the benefit of transcendental meditation intervention on SBP reduction.