Synthesis of three-arm block copolymer poly(lactic--glycolic acid)-poly(ethylene glycol) with oxalyl chloride and its application in hydrophobic drug delivery.

Purpose: Synthesis of star-shaped block copolymer with oxalyl chloride and preparation of micelles to assess the prospect for drug-carrier applications.

Materials And Methods: Three-arm star block copolymers of poly(lactic--glycolic acid) (3S-PLGA)-polyethylene glycol (PEG) were synthesized by ring-opening polymerization, then PEG as the hydrophilic block was linked to the terminal hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR) spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic resonance (H-NMR) spectra, and differential scanning calorimetry were employed to identify the structure and properties of 3S-PLGA-PEG.

Cellular membrane-anchored fluorescent probe with aggregation-induced emission characteristics for selective detection of Cu ions.

The exploration of advanced fluorescent probes that can detect divalent copper (Cu) in aqueous environments and even in live organisms is particularly valuable for understanding the occurrence and development of Cu-related diseases. In this work, we report the design and synthesis of an aggregation-induced emission luminogen (AIEgen)-based probe (TPE-Py-EEGTIGYG) by integrating an AIEgen, TPE-Py, with a peptide, EEGTIGYG, which can selectively detect Cu in both aqueous solution and live cells. Peptide EEGTIGYG has dual functionality in the probe design, namely improving water solubility and providing specific cell membrane-binding ability.

Real-Time Imaging Tracking of a Dual Fluorescent Drug Delivery System Based on Zinc Phthalocyanine-Incorporated Hydrogel.

Real-time tracking of a drug delivery system and its therapeutic effects in vivo are crucial to designing a novel pharmaceutical system and revealing the mechanism of drug therapy. Multispectral fluorescence imaging can locate the drug and carrier simultaneously without interference. This advanced method enables the tracking of a drug delivery system.

Correction: Guanidinylated cationic nanoparticles as robust protein antigen delivery systems and adjuvants for promoting antigen-specific immune responses in vivo.

Correction for 'Guanidinylated cationic nanoparticles as robust protein antigen delivery systems and adjuvants for promoting antigen-specific immune responses in vivo' by Pan Li et al., J. Mater.

Bridging the Gap between Macroscale Drug Delivery Systems and Nanomedicines: A Nanoparticle-Assembled Thermosensitive Hydrogel for Peritumoral Chemotherapy.

The objective of this study was to investigate the spatiotemporal delivery of nanomedicines by an injectable, thermosensitive, and nanoparticle-self-aggregated hydrogel for peritumoral chemotherapy. Doxorubicin (Dox) was taken as the model medicine, which was encapsulated into poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.

Nitric Oxide-Releasing Biomaterials for Biomedical Applications.

Nitric oxide (NO), as an essential signaling molecule, participates in various physiological processes such as cardiovascular homeostasis, neuronal transmission, immunomodulation, and tumor growth. The multiple role of NO in physiology and pathophysiology has triggered a massive interest in the strategies of delivering exogenous NO for biomedical applications. Hence, different kinds of NO prodrugs have been developed up to date, including diazeniumdiolates, S-nitrosothiol, metal-nitrosyl, nitrobenzene, and so on.

PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model.

Poly(lactic-co-glycolic acid) (PLGA) based nano/micro particles were investigated as a potential vaccine platform for pertussis antigen. Presentation of pertussis toxoid as nano/micro particles (NP/MP) gave similar antigen-specific IgG responses in mice compared to soluble antigen. Notably, in cell line based assays, it was found that PLGA based nano/micro particles enhanced the phagocytosis of fluorescent antigen-nano/micro particles by J774.

Guanidinylated cationic nanoparticles as robust protein antigen delivery systems and adjuvants for promoting antigen-specific immune responses in vivo.

Weak immunogenicity and transient humoral or cellular immune responses are the major limitations of modern protein vaccines. Using delivery adjuvants is a good strategy to promote their immune response in vivo. In this study, a type of guanidinylated and cationic nanoparticle adjuvant self-assembled by monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino)ethyl methacrylate)-block-poly(2-(guanidyl)ethyl methacrylate) (mPEG-b-PDPA-b-PGEM, PEDG) copolymers was used as an antigen delivery carrier.

Differences in the performance of PCL-based vascular grafts as abdominal aorta substitutes in healthy and diabetic rats.

Great progress has been made in the field of vascular tissue engineering, with some artificial vascular grafts already exhibiting promising outcomes in animal models. However, these studies were mostly conducted using healthy animals, which are not representative of actual clinical demands. Indeed, patients who require artificial vascular graft implantation are often accompanied by other comorbidities, such as hyperlipidaemia, hypertension and diabetes which should also be taken into consideration when assessing the potential of vascular grafts that are intended for clinical applications.

Dual actions of Netrin-1 on islet insulin secretion and immune modulation.

Netrin-1 is typically known as a neural guidance cue, which has been implicated in pancreas development. Since regenerative, angiogenic and anti-inflammatory properties of Netrin-1 have been reported in multiple tissues, we have investigated the potential role of Netrin-1 in the endocrine islet and its implication in mice with high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Effects of exogenous Netrin-1 on β-cell [Ca(2+)]i, cyclic AMP (cAMP) and insulin production were assessed in vitro The long-term impact of Netrin-1 treatment was then evaluated in HFD/STZ-induced diabetic mice by subcutaneous implantation of osmotic minipumps which release Netrin-1 in a sustained manner for 4 weeks.

Functional Modification of Fibrous PCL Scaffolds with Fusion Protein VEGF-HGFI Enhanced Cellularization and Vascularization.

The lack of efficient vascularization within frequently used poly(ε-caprolactone) (PCL) scaffolds has hindered their application in tissue engineering. Hydrophobin HGFI, an amphiphilic protein, can form a self-assembly layer on the surface of PCL scaffolds and convert their wettability. In this study, a fusion protein consisting of HGFI and vascular endothelial growth factor (VEGF) is prepared by Pichia pastoris expression system.

ECM-mimetic heparin glycosamioglycan-functionalized surface favors constructing functional vascular smooth muscle tissue in vitro.

Contractile vascular smooth muscle accounts for the normal physiological function of artery. Heparin, as a native glycosaminoglycan, has been well known for its important function in promoting or maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs). In this study, heparin-functionalized non-woven poly(ε-caprolactone) (PCL) mat was fabricated by a facile and efficient surface modification protocol, which enables the control of surface heparin density within a broad range.

Surface-Induced Hydrogelation for Fluorescence and Naked-Eye Detections of Enzyme Activity in Blood.

Fluorescence probes have been widely applied for the detection of important analytes with high sensitivity and specificity. However, they cannot be directly applied for the detection in samples with autofluorescence such as blood. Herein, we demonstrated a simple but effective method of surface-induced self-assembly/hydrogelation for fluorescence detection of an enzyme in biological fluids including blood and cell lysates.

Bone Marrow Is a Reservoir for Cardiac Resident Stem Cells.

Resident cardiac stem cells (CSCs) represent a responsive stem cell reservoir within the adult myocardium and have a significant function in myocardial homeostasis and injury. However, the distribution, origin, homing and possible therapeutic benefits of CSCs are still under discussion. Here we investigated whether bone marrow (BM) stem cells could contribute to repopulating the pool of CSCs in heart.

An Activatable Theranostic Nanomedicine Platform Based on Self-Quenchable Indocyanine Green-Encapsulated Polymeric Micelles.

Self-quenchable indocyanine green (ICG)-encapsulated micelles with folic acid (FA)-targeting specificity (FA-ICG-micelles) were developed for biologically activatable photodynamic theranostics. FA-ICG-micelles were successfully prepared using the thin-film hydration method, which allows ICG to be encapsulated with a high drug loading that induces an efficient ICG-based quenched state. FA-ICG-micelles are initially in the "OFF" state with no fluorescence signal or phototoxicity, but they become highly fluorescent and phototoxic in cellular degradative environments.

Activatable Fluorescent Nanoprobe with Aggregation-Induced Emission Characteristics for Selective In Vivo Imaging of Elevated Peroxynitrite Generation.

An activatable fluorescent nanoprobe with aggregation-induced emission signature is developed. The nanoprobe is nonfluorescent, but can be induced to emit intensely after reaction with peroxynitrite forming an intramolecular hydrogen bond. Excellent performance for selective in vivo imaging of inflammation with elevated peroxynitrite generation and efficient visualization of in vivo treatment efficacy of anti-inflammatory agents is demonstrated.

Hyaluronic Acid-Modified Cationic Lipid-PLGA Hybrid Nanoparticles as a Nanovaccine Induce Robust Humoral and Cellular Immune Responses.

Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred. Moreover, HA-DOTAP-PLGA NPs led to the up-regulation of MHC, costimulatory molecules, and cytokines.

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors.

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo.

Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects.

Cancer development and progression is linked to tumor-associated macrophages (TAMs). Distinct TAMs subsets perform either protective or pathogenic effects in cancer. A protective role in carcinogenesis has been described for M1 macrophages, which activate antitumor mechanisms.

Far-red/near-infrared fluorescence light-up probes for specific in vitro and in vivo imaging of a tumour-related protein.

As lysosomal protein transmembrane 4 beta (LAPTM4B) is an important biomarker for many solid tumours, development of small-molecule fluorescence light-up probes for detection and imaging of LAPTM4B proteins is particularly valuable. In this work, we reported the design and synthesis of a far-red/near-infrared (FR/NIR) fluorescence light-up probe DBT-2EEGIHGHHIISVG, which could specifically visualize LAPTM4B proteins in cancer cells and tumour-bearing live mice. DBT-2EEGIHGHHIISVG was synthesized by the conjugation of two LAPTM4B-binding peptide ligands (EEGIHGHHIISVG) with one environment-sensitive fluorogen, 4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole (DBT).

Peptide-Induced AIEgen Self-Assembly: A New Strategy to Realize Highly Sensitive Fluorescent Light-Up Probes.

Fluorescent light-up probes with aggregation-induced emission (AIE) characteristics have recently attracted great research interest due to their intelligent fluorescence activation mechanism and excellent photobleaching resistance. In this work, we report a new, simple, and generic strategy to design and prepare highly sensitive AIE fluorescent light-up bioprobe through facile incorporation of a self-assembling peptide sequence GFFY between the recognition element and the AIE luminogen (AIEgen). After the bioprobes respond to the targets, the peptide GFFY is capable of inducing the ordered self-assembly of AIEgens, yielding close and tight intermolecular steric interactions to restrict the intramolecular motions of AIEgens for excellent signal output.

Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer.

Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff's base reaction.

IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI.

Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model.

Effects of glucose metabolism during in vitro maturation on cytoplasmic maturation of mouse oocytes.

Although there are many reports on the effect of glucose metabolism on oocyte nuclear maturation, there are few studies on its effect on ooplasmic maturation. By manipulating glucose metabolism pathways using a maturation medium that could support oocyte nuclear maturation but only a limited blastocyst formation without glucose, this study determined effects of glucose metabolism pathways on ooplasmic maturation. During maturation of cumulus-oocyte-complexes (COCs) with glucose, the presence of PPP inhibitor, DHEA or glycolysis inhibitor, iodoacetate significantly decreased blastocyst rates, intraoocyte glutathione and ATP.