PDL1/HER2-Targeted Lipid-Encapsulated Oxygen Nanobubbles Combined with Photodynamic Therapy for HER2 Breast Cancer Immunotherapy.

Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint inhibitors (ICIs) that may facilitate HER2-positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen-enhanced photodynamic therapy (PDT) increases immunogenic cell death (ICD), providing a promising strategy to render the tumor microenvironment more sensitive to the ICIs. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O) obtained using nanobubbles (NBs) water for oxygen delivery in vivo can facilitate enhanced PDT.

Anti-HER2 scFv-nCytc-Modified Lipid-Encapsulated Oxygen Nanobubbles Prepared with Bulk Nanobubble Water for Inducing Apoptosis and Improving Photodynamic Therapy.

Bulk nanobubbles fascinate scientists because of their stability over long periods of time and their ability to carry gases, leading to numerous potential applications. Considering the hypoxic tumor microenvironment and the advantages of bulk nanobubbles, lipid-encapsulated oxygen nanobubbles are prepared from free bulk oxygen nanobubbles in this study. The obtained carrier is then modified with a protein fused with the single-chain antibody of human epidermal growth factor receptor 2 (anti-HER2 scFv) and tandem-repeat cytochrome c (anti-HER2 scFv-nCytc) to enhance tumor targeting and induce tumor apoptosis.

Preparation, characterization, and antibacterial activity of tigecycline-loaded, ultrasound-activated microbubbles.

Central nervous system infectious disease caused by the multidrug-resistant () seriously threatens human life in clinic. Tigecycline has good sensitivity in killing , but due to its wide tissue distribution and blood-brain barrier, concentration in cerebrospinal fluid is low, therefore, the clinical effect is limited. Herein, we designed micro-bubbled tigecycline, aimed to enhance its anti-MDRAB effects under ultrasound.

Transplantation of mesenchymal stem cells ameliorates systemic lupus erythematosus and upregulates B10 cells through TGF-β1.

Background: Considerable experimental and clinical evidences have proved that human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation was powerful in systemic lupus erythematosus (SLE) treatment. MSCs could upregulate regulatory B cells (Bregs) in the mice model of the other immune disease. However, the regulation of MSCs on Bregs in SLE environment remains unclear.

Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis.

Cell swelling and membrane blebbing are characteristic of pyroptosis. In the present study, we explored the role of intracellular tension activity in the deformation of pyroptotic astrocytes. Protein nanoparticle-induced osmotic pressure (PN-OP) was found to be involved in cell swelling and membrane blebbing in pyroptotic astrocytes, and was associated closely with inflammasome production and cytoskeleton depolymerization.

Bazedoxifene is a novel IL-6/GP130 inhibitor for treating triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) has been ranked as one of the devastating malignancy worldwide. Its disease progression and treatment obstacle is associated with the negligible expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 (HER2). Due to a lack of growth hormone receptors, TNBC is desperately demanding effective therapeutic regimens.

Talin promotes integrin activation accompanied by generation of tension in talin and an increase in osmotic pressure in neurite outgrowth.

Neuronal polarization depends on the interaction of intracellular chemical and mechanical activities in which the cytoplasmic protein, talin, plays a pivotal role during neurite growth. To better understand the mechanism underlying talin function in neuronal polarization, we overexpressed several truncated forms of talin and found that the presence of the rod domain within the overexpressed talin is required for its positive effect on neurite elongation because the neurite number only increased when the talin head region was overexpressed. The tension in the talin rod was recognized using a Förster resonance energy transfer-based tension probe.

Down-regulating IL-6/GP130 targets improved the anti-tumor effects of 5-fluorouracil in colon cancer.

Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor.

Blocking IL-6/GP130 Signaling Inhibits Cell Viability/Proliferation, Glycolysis, and Colony Forming Activity in Human Pancreatic Cancer Cells.

Background: Elevated production of the pro-inflammatory cytokine interleukin-6 (IL-6) and dysfunction of IL-6 signaling promotes tumorigenesis and are associated with poor survival outcomes in multiple cancer types. Recent studies showed that the IL-6/GP130/STAT3 signaling pathway plays a pivotal role in pancreatic cancer development and maintenance.

Objective: We aim to develop effective treatments through inhibition of IL-6/GP130 signaling in pancreatic cancer.

Paclitaxel-Loaded Magnetic Nanoparticles: Synthesis, Characterization, and Application in Targeting.

Iron oxide magnetic nanoparticles (MNPs) are good candidates to implement fluid therapy in critical patients in clinic integrated system. Herein, we synthesized paclitaxel (PTX)-loaded MNPs modified with methoxy polyethylene glycol (PEG)-lysine-oleic acid (PTX-MNPs-PLO), which is expected to act as a magnetic resonance imaging (MRI) contrast agent and meanwhile for cancer therapy. MNPs were synthesized by thermal decomposition.

Ultrasound mediated delivery of oxygen and LLL12 loaded stimuli responsive microdroplets for the treatment of hypoxic cancer cells.

LLL12 exhibits high specificity for inhibiting STAT3 phosphorylation and dimerization, and inducing apoptosis to constitutively activated STAT3 cancer cells without cytotoxicity to normal cells with dormant STAT3. However, clinical deployment of LLL12 in cancer treatment is hindered by its low bioavailability and hypoxia-induced resistance. To overcome these limitations, we encapsulate both oxygen and LLL12 in stimuli responsive microdroplets (SRMs) by a gas-driven coaxial flow focusing (CFF) process for ultrasound mediated treatment of hypoxic cancer cells.

The Antiproliferative and Colony-suppressive Activities of STAT3 Inhibitors in Human Cancer Cells Is Compromised Under Hypoxic Conditions.

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors.

Superparamagnetic anisotropic nano-assemblies with longer blood circulation in vivo: a highly efficient drug delivery carrier for leukemia therapy.

Leukemia, unlike solid tumors, has no definite shape and spreads throughout the whole circulatory system, therefore the therapy of leukemia requires medication to stay longer in the circulatory system. Anisotropic nanoparticles, showing longer blood circulating life than that of isotropic nanoparticles reported in previous research, meet the demands of leukemia therapy. Based on this strategy, superparamagnetic anisotropic nano-assemblies (SANs) were fabricated and loaded with vincristine (VCR) to form VCR-SANs.

A Novel Approach to Making the Gas-Filled Liposome Real: Based on the Interaction of Lipid with Free Nanobubble within the Solution.

Nanobubbles with a size less than 1 μm could make a promising application in ultrasound molecular imaging and drug delivery. However, the fabrication of stable gas encapsulation nanobubbles is still challenging. In this study, a novel method for preparation of lipid- encapsulated nanobubbles was reported.

Controlled assembly of magnetic nanoparticles on microbubbles for multimodal imaging.

Magnetic microbubbles (MMBs) consisting of microbubbles (MBs) and magnetic nanoparticles (MNPs) were synthesized for use as novel markers for improving multifunctional biomedical imaging. The MMBs were fabricated by assembling MNPs in different concentrations on the surfaces of MBs. The relationships between the structure, magnetic properties, stability of the MMBs, and their use in magnetic resonance/ultrasound (MR/US) dual imaging applications were determined.

2, 3-dimercaptosuccinic acid-modified iron oxide clusters for magnetic resonance imaging.

Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2 O3 @DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2 O3 @DMSA with the size of 156.

A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects.

Liver cancer has become one of the most common fatal cancers worldwide, with morbidity rates increasing each year. Wogonin (WG) is an attractive candidate for the development of new anti-cancer drugs. In this study, a novel glycyrrhetinic acid (GA)-modified WG liposome was developed for use in targeted anti-cancer therapy.

Selection of high efficient transdermal lipid vesicle for curcumin skin delivery.

Curcumin shows effective anti-inflammatory activities but is seldom used in clinic because of its poor solubility in water and vulnerablity to sunshine ultraviolet effect. Novel lipid vesicles have been developed as carriers for skin delivery. In this paper, lipid vesicles-propylene glycol liposomes (PGL), Ethosomes and traditional liposomes, were prepared as curcumin carriers respectively.

[Micromeritic evaluation of the direct compression excipient LubriTose AN].

This study is to report the evaluation of the micromeritic properties of LubriTose AN, which is expected to provide preliminary theoretical basis for the direct compression technology. From the aspects of flowability, compressibility and dilution potential, the angle of repose, flow velocity, the Carr' index, tensile strength, elastic recovery, yield pressure and the lubricating ability of LubriTose AN were determined. Also, model drugs were selected to investigate the dilute potential under the desirable compressing performance.

Improving the cardio protective effect of aFGF in ischemic myocardium with ultrasound-mediated cavitation of heparin modified microbubbles: preliminary experiment.

Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method.

The anti-tumor performance of docetaxel liposomes surface-modified with glycyrrhetinic acid.

Purpose: Anti-tumor performance of docetaxel liposomes surface-modified with glycyrrhetinic acid (GA-DX-Lip) as a new hepatocytes-targeted delivery vehicle was investigated, unmodified docetaxel liposome (DX-Lip) was chosen as a comparison.

Methods: GA-DX-Lip was prepared by film dispersion method. The physicochemical properties were characterized.

[Transport of limonin in rat intestine in situ and Caco-2 cells in vitro].

Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use.

Synthesis and characterization of Poloxamer 188-grafted heparin copolymer.

Background: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system.

Aim: In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy ((1)H-NMR).

Enhancing chemotherapeutic drug inhibition on tumor growth by ultrasound: an in vivo experiment.

An in vivo study on enhancing epirubicin hydrochloride (EPI) inhibition on tumor growth by ultrasound (US) was reported. Five-week-old male nude mice were used and HL-60 cells were s.c.