Tumor-specific cytolysis by peptide-conjugated echogenic polymer micelles.

Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate.

Rapid Assessment of Di(2-ethylhexyl) Phthalate Migration from Consumer PVC Products.

Poly(vinyl chloride) (PVC) is widely used to produce various consumer goods, including food packaging, toys for children, building materials, and cosmetic products. However, despite their widespread use, phthalate plasticizers have been identified as endocrine disruptors, which cause adverse health effects, thus leading to increasing concerns regarding their migration from PVC products to the environment. This study proposed a method for rapidly measuring the migration of phthalates, particularly di(2-ethylhexyl) phthalate (DEHP), from PVC products to commonly encountered liquids.

Multi-Functional Polymer Nanoparticles with Enhanced Adipocyte Uptake and Adipocytolytic Efficacy.

Multi-functional polymer nanoparticles have been widely utilized to improve cellular uptake and enhance therapeutic efficacy. In this study, it is hypothesized that the cellular uptake of poly(D,L-lactide-co-glycolide) (PLG) nanoparticles loaded with calcium carbonate minerals into adipocytes can be improved by covalent modification with nona-arginine (R ) peptide. It is further hypothesized that the internalization mechanism of R -modified PLG nanoparticles by adipocytes may be contingent on the concentration of R peptide present in the nanoparticles.

Adipocytolytic Polymer Nanoparticles for Localized Fat Reduction.

The demand for body fat reduction is increasing. However, conventional lipolytic approaches fail to control adipose tissue reduction and cause severe side effects in adjacent nonadipose tissues. A strategy to specifically reduce subcutaneous fat using adipocytolytic polymer nanoparticles in a minimally invasive manner is reported here.

Intracellular Glucose-Depriving Polymer Micelles for Antiglycolytic Cancer Treatment.

A new anticancer strategy to exploit abnormal metabolism of cancer cells rather than to merely control the drug release or rearrange the tumor microenvironment is reported. An antiglycolytic amphiphilic polymer, designed considering the unique metabolism of cancer cells (Warburg effect) and aimed at the regulation of glucose metabolism, is synthesized through chemical conjugation between glycol chitosan (GC) and phenylboronic acid (PBA). GC-PBA derivatives form stable micellar structures under physiological conditions and respond to changes in glucose concentration.

Three-dimensional printing of hyaluronate-based self-healing ferrogel with enhanced stretchability.

Hydrogels have been frequently employed for three-dimensional (3D) printing, which is a promising tool for fabricating sophisticated structures useful in many biomedical applications. Ferrogels prepared by combining magnetic nanoparticles with hydrogels also have potential in biomedical engineering because of the responsiveness to a magnetic field and remotely controllable properties. However, typical ferrogels, especially those prepared from natural polysaccharides, have limitations concerning their mechanical properties and the fabrication method of complex structures owing to their rigid and brittle properties.

Stretchable and self-healable hyaluronate-based hydrogels for three-dimensional bioprinting.

Hydrogels have been widely exploited as inks for three-dimensional (3D) bioprinting, a useful technique for building complex biological structures with living cells. However, hydrogels have inherently limited mechanical properties (e.g.

In vitro culture of hematopoietic stem cell niche using angiopoietin-1-coupled alginate hydrogel.

Stem cells exist and maintain their quiescence and pluripotency in stem cell niche. Here, we hypothesized that regulation of cell-cell interactions using a polymeric scaffold as synthetic extracellular matrix (ECM) could be critical in creating a hematopoietic stem cell (HSC) niche in vitro. Angiopoietin-1 (Ang1) binds to the tyrosine kinase receptor (Tie2), and regulation of the Tie2/Ang1 interaction is important in maintaining the quiescence of HSCs in vivo.

In Vitro Cellular Uptake and Transfection of Oligoarginine-Conjugated Glycol Chitosan/siRNA Nanoparticles.

Chitosan and its derivatives have been extensively utilized in gene delivery applications because of their low toxicity and positively charged characteristics. However, their low solubility under physiological conditions often limits their application. Glycol chitosan (GC) is a derivative of chitosan that exhibits excellent solubility in physiological buffer solutions.

Three-dimensional bioprinting of polysaccharide-based self-healing hydrogels with dual cross-linking.

Three-dimensional (3D) bioprinting technique is useful to fabricate constructs with functional and biological structures for various biomedical applications. Oxidized hyaluronate (OHA) and glycol chitosan (GC) can form autonomous self-healing hydrogels when adipic acid dihydrazide (ADH) is used. We demonstrate that hyaluronate-alginate hybrid (HAH) polymers can be used for secondary physical cross-linking of OHA/GC/ADH hydrogel with calcium ions after 3D printing.

3D Printing of Polysaccharide-Based Self-Healing Hydrogel Reinforced with Alginate for Secondary Cross-Linking.

Three-dimensional (3D) bioprinting has been attractive for tissue and organ regeneration with the possibility of constructing biologically functional structures useful in many biomedical applications. Autonomous healing of hydrogels composed of oxidized hyaluronate (OHA), glycol chitosan (GC), and adipic acid dihydrazide (ADH) was achieved after damage. Interestingly, the addition of alginate (ALG) to the OHA/GC/ADH self-healing hydrogels was useful for the dual cross-linking system, which enhanced the structural stability of the gels without the loss of their self-healing capability.

3D Printing of dynamic tissue scaffold by combining self-healing hydrogel and self-healing ferrogel.

Hydrogels have been widely utilized in tissue engineering applications as functional and biological synthetic extracellular matrices (ECMs) can be created with gels. However, typical hydrogels cannot be exploited in 3D printing, especially in extrusion printing, unless post-cross-linking after printing is provided. Additionally, dynamic tissue scaffolds that can mimic ECM environments in the body have been demonstrated to be useful in tissue engineering.

On/off switchable physical stimuli regulate the future direction of adherent cellular fate.

The utilization of cell-manipulating techniques reveals information about biological behaviors suited to address a wide range of questions in the field of life sciences. Here, we introduced an on/off switchable physical stimuli technique that offers precise stimuli for reversible cell patterning to allow regulation of the future direction of adherent cellular behavior by leveraging enzymatically degradable alginate hydrogels with defined chemistry and topography. As a proof of concept, targeted muscle cells adherent to TCP exhibited a reshaped structure when the hydrogel-based physical stimuli were applied.

3D printing of self-healing ferrogel prepared from glycol chitosan, oxidized hyaluronate, and iron oxide nanoparticles.

Hydrogel systems that show self-healing ability after mechanical damage are receiving increasing attention. However, self-healing hydrogels suitable for biomedical applications are limited owing to complex preparation methods. Furthermore, few studies have demonstrated the self-healing property of ferrogels.

Regulation of the Viscoelastic Properties of Hyaluronate-Alginate Hybrid Hydrogel as an Injectable for Chondrocyte Delivery.

Modulation of the viscoelastic properties of hydrogels is critical in tissue engineering applications. In the present study, a hyaluronate-alginate hybrid (HAH) was synthesized by introducing alginate to the hyaluronate backbone with varying molecular weights (700-2500 kDa), and HAH hydrogels were prepared in the presence of calcium ions at the same cross-linking density. The storage shear moduli of the HAH hydrogels increased with the concomitant increase in the molecular weight of hyaluronate in the HAH polymer.

Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain.

Controlling the porous structure of alginate ferrogel for anticancer drug delivery under magnetic stimulation.

Stimulus-responsive drug delivery systems have been widely used for many biomedical applications. Magnetic stimulation may serve as an important external stimulus for drug delivery. In this study, we hypothesized that the on-demand release of anticancer drugs could be achieved with a macroporous alginate ferrogel under the influence of magnetic stimulation to enhance therapeutic efficacy in a tumor-bearing mouse model.

Hyaluronate-alginate hybrid hydrogels prepared with various linkers for chondrocyte encapsulation.

Tissue engineering typically requires a use of scaffolds when delivering tissue-specific cells to be engineered. Hydrogels are frequently used as scaffolds, because their composition, structure, and function resemble the natural tissue extracellular matrix. In this study, hyaluronate-alginate hybrid (HAH) was synthesized by conjugating alginate (ALG) with the hyaluronate (HA) backbone using various types of linkers.

Three-Dimensional Bioprinting of Cell-Laden Constructs Using Polysaccharide-Based Self-Healing Hydrogels.

Development of biomaterial-based bioinks is critical for replacement and/or regeneration of tissues and organs by three-dimensional (3D) printing techniques. However, the number of 3D-printable biomaterials in practical use remains limited despite the rapid development of 3D printing techniques. Controlling the flow properties of bioinks and mechanical properties of the resultant printed objects is key considerations in the design of biomaterial-based bioinks for practical applications.

Hyaluronate-alginate hybrid hydrogels modified with biomimetic peptides for controlling the chondrocyte phenotype.

Hyaluronate-based hydrogels have been widely exploited as synthetic extracellular matrices in many tissue engineering applications, including cartilage tissue engineering. Hyaluronate-based hydrogels are typically prepared by chemical cross-linking reactions, in which chemical reagents may induce side effects, unless they are completely removed after the cross-linking reaction. We thus suggest the utilization of hybrid materials composed of hyaluronate as a main chain and alginate for physical cross-linking to simply form hydrogels in the presence of calcium ions under physiological conditions.

Sequential Targeted Delivery of Liposomes to Ischemic Tissues by Controlling Blood Vessel Permeability.

Delivery systems for therapeutic angiogenesis that deliver angiogenic factors to ischemic tissues have recently been fabricated. However, these systems are designed for surgical implantation or multiple local injections which can cause pain and potential physical burden in patients. Here, we propose a minimally invasive sequential nanoparticle-mediated delivery strategy for ischemic tissue using a murine hindlimb ischemic model.

Carbon Dioxide-Generating PLG Nanoparticles for Controlled Anti-Cancer Drug Delivery.

Purpose: Poly(D,L-lactide-co-glycolide) (PLG) nanoparticles containing doxorubicin and mineralized calcium carbonate were fabricated and their anti-tumor efficacy was tested using a neuroblastoma-bearing mouse model.

Methods: PLG nanoparticles were prepared by a double emulsion (water-in-oil-in-water; W/O/W) method. Calcium carbonate was mineralized within the PLG nanoparticles during the emulsion process.

Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation.

Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells.

Alginate hydrogels modified with low molecular weight hyaluronate for cartilage regeneration.

Alginate is a typical biomaterial that forms hydrogels in the presence of calcium ions and has often been utilized in tissue engineering approaches. However, it lacks biofunctionality in the form of interactions with cells and proteins. Hyaluronate, a main component of glycosaminoglycans, provides CD44-specific interactions with chondrocytes but typically requires chemical cross-linking agents to fabricate hydrogels, which may cause unexpected side effects in the body.

Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles.