Comparative In Vivo Study of Solid-Type Pure Hyaluronic Acid in Thread Form: Safety and Efficacy Compared to Hyaluronic Acid Filler and Polydioxanone Threads.

INTRODUCTION: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. METHOD: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. RESULTS: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-ß1 compared to the HA group. CONCLUSION: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Comparison of Open-Construct PEEK Suture Anchor and Non-Vented Biocomposite Suture Anchor in Arthroscopic Rotator Cuff Repair: A Prospective Randomized Clinical Trial.

PURPOSE: To compare radiologic bone ingrowth and the clinical outcomes of an open-construct (PEEK) (polyether ether ketone) suture anchor with those of a non-vented biocomposite suture anchor in patients with arthroscopic rotator cuff repair. METHODS: Sixty-nine patients were randomly allocated into 2 groups based on type of suture anchors used for rotator cuff repair; group 1: open-construct PEEK anchor (36 patients), group 2: non-vented biocomposite anchor (33 patients). The status of bone ingrowth into the anchor and the presence of cyst formation were evaluated at 6 months postoperatively by computed tomography scan using the Modified Barber's ossification scale. The American Shoulder and Elbow Surgeons score, Constant score, and visual analog scale score for pain and range of motion were evaluated. Magnetic resonance imaging or ultrasonography was performed at 12 months postoperatively to examine the integrity of the repaired rotator cuff tendon. RESULTS: Significant improvements in shoulder function and pain relief were observed regardless of the anchor used (both Group 1 and 2; P < .001). No differences were found in functional scores and range of motion between the 2 groups. Group 1 showed better bone ingrowth grades than group 2 (poor 2.8 vs 24.2%, fair 27.8 vs 39.4%, good 38.9 vs 33.3%, and excellent 30.6 vs 3.0%; P < .001). The rate of cyst formation around the anchor on the 6 months' postoperative computed tomography (group 1: 14% and group 2: 12%) and re-tear rate at 12 months (5% each) showed no difference between the 2 groups. CONCLUSIONS: Shoulder function was improved after complete rotator cuff repair and similar clinical outcomes were achieved regardless of suture anchor material and shape. However, the open-construct PEEK anchor provided better bone ingrowth into the anchor than the non-vented biocomposite anchor at 6 months after arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: Level I; Prospective Randomized Trial.

Adjustable Intermolecular Interactions Allowing 2D Transition Metal Dichalcogenides with Prolonged Scavenging Activity for Reactive Oxygen Species.

There is an increasing demand for control over the dimensions and functions of transition metal dichalcogenides (TMDs) in aqueous solution toward biological and medical applications. Herein, an approach for the exfoliation and functionalization of TMDs in water via modulation of the hydrophobic interaction between poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) and the basal planes of TMDs is reported. Decreasing the hydrophobic PCL length of PCL-b-PEG from 5000 g mol-1 (PCL5000 ) to 460 g mol-1 (PCL460 ) significantly increases the exfoliation efficiency of TMD nanosheets because the polymer-TMD hydrophobic interaction becomes dominant over the polymer-polymer interaction. The TMD nanosheets exfoliated by PCL460 -b-PEG5000 (460-WS2 , 460-WSe2 , 460-MoS2 , and 460-MoSe2 ) show excellent and prolonged scavenging activity for reactive oxygen species (ROS), but each type of TMD displays a different scavenging tendency against hydroxyl, superoxide, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. A mechanistic study based on electron paramagnetic resonance spectroscopy and density functional theory simulations suggests that radical-mediated oxidation of TMDs and hydrogen transfer from the oxidized TMDs to radicals are crucial steps for ROS scavenging by TMD nanosheets. As-prepared 460-TMDs are able to effectively scavenge ROS in HaCaT human keratinocytes, and also exhibit excellent biocompatibility.

Sphere formation of adipose stem cell engineered by poly-2-hydroxyethyl methacrylate induces in vitro angiogenesis through fibroblast growth factor 2.

A number of researchers have been reporting a wide range of in vitro and in vivo studies of cell engraftment to enhance angiogenesis using stem cells. Despite these efforts, studies involving three-dimensional (3D) culture method that mimics in vivo environment have not reached its peak yet. In this study, we investigated the change and effects on cellular angiogenic growth factors through sphere formation of adipose stem cell (ASC) which is engineered by poly-2-hydroxyethyl methacrylate (Poly-HEMA). First of all, we successfully induced sphere formation of ASC (sph-ASC) on Poly-HEMA coated plates. sph-ASC represented significantly higher expression levels of anti-apoptotic and hypoxic factors compared to monolayer adherent ASC (adh-ASC). Interestingly, sph-ASC showed higher mRNA levels of the following genes; CD31, CD144, vWF, IGF-2, MCP-1, PDGF-A, VEGF-A, VEGF-C, and FGF-2. In addition, mRNA expressions of angiogenic growth factor receptors such as Flk1, FGFR1, FGFR2, and Tie2 were elevated in sph-ASC. In protein level, Cytokine/Chemokines antibody array revealed a significant increase of FGF-2 in sph-ASC (3.17-fold) compared to adh-ASC. To investigate the effects of FGF-2 on sph-ASC, Matrigel angiogenic invasion assay showed significant reduced level of FGF-2 in FGF-2 siRNA transfected sph-ASC (2.27-fold) compared to negative control siRNA transfected sph-ASC. These findings suggest that Poly-HEMA coated plates induce sphere formation of ASC which has significantly higher expression of FGF-2, and plays a critical role as a major regulating growth factor of in vitro angiogenesis.

Improving difficult direct laryngoscopy prediction using deep learning and minimal image analysis: a single-center prospective study.

Accurate prediction of difficult direct laryngoscopy (DDL) is essential to ensure optimal airway management and patient safety. The present study proposed an AI model that would accurately predict DDL using a small number of bedside pictures of the patient's face and neck taken simply with a smartphone. In this prospective single-center study, adult patients scheduled for endotracheal intubation under general anesthesia were included. Patient pictures were obtained in frontal, lateral, frontal-neck extension, and open mouth views. DDL prediction was performed using a deep learning model based on the EfficientNet-B5 architecture, incorporating picture view information through multitask learning. We collected 18,163 pictures from 3053 patients. After under-sampling to achieve a 1:1 image ratio of DDL to non-DDL, the model was trained and validated with a dataset of 6616 pictures from 1283 patients. The deep learning model achieved a receiver operating characteristic area under the curve of 0.81-0.88 and an F1-score of 0.72-0.81 for DDL prediction. Including picture view information improved the model's performance. Gradient-weighted class activation mapping revealed that neck and chin characteristics in frontal and lateral views are important factors in DDL prediction. The deep learning model we developed effectively predicts DDL and requires only a small set of patient pictures taken with a smartphone. The method is practical and easy to implement.

Long-term outcomes after core extirpation of fibrous dysplasia of the zygomaticomaxillary region.

BACKGROUND: Fibrous dysplasia (FD) is a localized bone disorder in which fibro-osseous tissue replaces the normal bone structure. Patients with craniofacial FD often present with gradual swelling, deformity, and compromised vision or hearing. We previously introduced "the core extirpation method," a novel surgical technique that is minimally invasive like traditional bone shaving but has longer-lasting effects. This study presents the long-term outcomes of our core extirpation method. METHODS: We conducted a retrospective analysis of patients who underwent core extirpation for FD of the zygomaticomaxillary region from 2012 through 2021. Computed tomography (CT) scans were performed 6 to 12 months before the operation, immediately before and after the operation, and during follow-up visits. We performed all operations using the upper gingivobuccal approach, and we extirpated the core of the lesion while preserving the cortical structures of the zygoma and the maxilla to maintain symmetrical facial contour. RESULTS: In 12 patients with lesions in the growth phase, anteroposterior/mediolateral (AP/ML) length discrepancies and the volume increased between preoperative and immediate postoperative CT scans. All patients' immediate postoperative AP/ML discrepancies were stable up to 12-17 months postoperatively. Postoperative volume showed continuous lesion growth; the median volume growth rate was 0.61 cc per month. CONCLUSION: In this article, we present our experiences managing FD using the minimally invasive core extirpation technique, which entails small expected blood loss and can be performed as day surgery. It provides similar cosmetic outcomes as traditional bone shaving but with longer-lasting results. Although there are some limitations with the study's retrospective nature and small sample size, our 4-year follow-up results show promising results of the core extirpation method in well-indicated patients.

Durability of heat-treated Paulownia tomentosa and Pinus koraiensis woods in palm oil and air against brown- and white-rot fungi.

This study aimed to evaluate and compare the effects of oil- and air-heat treatments on the durability of Paulownia tomentosa and Pinus koraiensis woods against Fomitopsis palustris and Trametes versicolor. The wood samples were treated in palm oil and air at 180, 200, and 220 °C for 2 h. The weight loss, morphology, crystalline properties, and chemical compounds of untreated and heat-treated wood after fungal attack were investigated. The significant difference in weight loss between oil- and air-heat-treated samples was shown at 220 °C. Heat-treated wood exposed to white-rot fungus showed a lower weight loss than that exposed to brown-rot fungus. The cell components in the untreated- and heat-treated Paulownia tomentosa and Pinus koraiensis at 180 °C were severely damaged due to fungal exposure compared to those at 220 °C. A fungal effect on the relative crystallinity was observed in heat-treated wood at 180 °C, whereas the effect was not observed at 220 °C. Following brown-rot fungus exposure, untreated- and heat-treated wood at 180 °C showed a notable change in the Fourier transform infrared (FTIR) peaks of polysaccharides, whereas no noticeable change in lignin peaks was observed. Heat-treated wood at 220 °C showed no noticeable change in the FTIR spectra owing to brown-rot fungus exposure. Exposure to white-rot fungus did not noticeably change the FTIR spectra of untreated and heat-treated wood.

A structure-function relationship for the optical modulation of phenyl boronic acid-grafted, polyethylene glycol-wrapped single-walled carbon nanotubes.

Phenyl boronic acids (PBA) are important binding ligands to pendant diols useful for saccharide recognition. The aromatic ring can also function to anchor an otherwise hydrophilic polymer backbone to the surface of hydrophobic graphene or carbon nanotube. In this work, we demonstrate both functions using a homologous series of seven phenyl boronic acids conjugated to a polyethylene glycol, eight-membered, branched polymer (PPEG8) that allows aqueous dispersion of single-walled carbon nanotubes (SWNT) and quenching of the near-infrared fluorescence in response to saccharide binding. We compare the 2-carboxyphenylboronic acid (2CPBA); 3-carboxy- (3CPBA) and 4-carboxy- (4CPBA) phenylboronic acids; N-(4-phenylboronic)succinamic acid (4SCPBA); 5-bromo-3-carboxy- (5B3CPBA), 3-carboxy-5-fluoro- (5F3CPBA), and 3-carboxy-5-nitro- (5N3CPBA) phenylboronic acids, demonstrating a clear link between SWNT photoluminescence quantum yield and boronic acid structure. Surprisingly, quantum yield decreases systematically with both the location of the BA functionality and the inclusion of electron-withdrawing or -donating substituents on the phenyl ring. For three structural isomers (2CPBA, 3CPBA, and 4CPBA), the highest quantum yields were measured for para-substituted PBA (4CPBA), much higher than ortho- (2CPBA) and meta- (3CPBA) substituted PBA, indicating the first such dependence on molecular structure. Electron-withdrawing substituents such as nitro groups on the phenyl ring cause higher quantum yield, while electron-donating groups such as amides and alkyl groups cause a decrease. The solvatochromic shift of up to 10.3 meV was used for each case to estimate polymer surface coverage on an areal basis using a linear dielectric model. Saccharide recognition using the nIR photoluminescence of SWNT is demonstrated, including selectivity toward pentoses such as arabinose, ribose, and xylose to the exclusion of the expected fructose, which has a high selectivity on PBA due to the formation of a tridentate complex between fructose and PBA. This study is the first to conclusively link molecular structure of an adsorbed phase to SWNT optical properties and modulation in a systematic manner.

Removal of particulate matter in a tubular wet electrostatic precipitator using a water collection electrode.

As one of the effective control devices of air pollutants, the wet electrostatic precipitator (ESP) is an effective technique to eliminate acid mist and fine particles that are re-entrained in a collection electrode. However, its collection efficiency can deteriorate, as its operation is subject to water-induced corrosion of the collection electrode. To overcome this drawback, we modified the wet ESP system with the installation of a PVC dust precipitator wherein water is supplied as a replacement of the collection electrode. With this modification, we were able to construct a compact wet ESP with a small specific collection area (SCA, 0.83 m(2)/(m(3)/min)) that can acquire a high collection efficiency of fine particles (99.7%).

Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy.

Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(beta-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.

Multilayer fluorescence optically encoded beads for protein detection.

An easy preparation method of multilayer fluorescence optically encoded beads for protein detection is presented. The beads, which consist of multicolored layers, are made from amino polyethylene glycol grafted polystyrene (PS-g-PEG) beads by using several fluorescent dyes such as fluorescein isothiocyanate (FITC) and rhodamine via controlling diffusion of an Fmoc-protecting group after HCl solution swelling. A biotin, glutathione S-transferase (GST) antibody, and an RNA aptamer that specifically recognize streptavidin, GST antigen, and hepatitis C virus (HCV) helicase are introduced to the optically encoded beads and monitored for their binding activity to the target molecules. After binding, the ligands are identified easily by their color codes.

Hypoxia-responsive folic acid conjugated glycol chitosan nanoparticle for enhanced tumor targeting treatment.

Hypoxia is a characteristic feature of various ischemic diseases, including cancer. This study describes the development of glycol chitosan nanoparticles, hydrophobically modified with 4-nitrobenzyl chloroformate and folic acid (FA), that can specifically release drugs under hypoxic conditions. This hypoxia-responsive glycol chitosan nanoparticle conjugated with FA (HRGF) possesses tumor-targeting properties by virtue of conjugated FA and is able to release drugs in a nitroreductase (NTR)-dependent manner because its structure is cleaved by NTR under hypoxic conditions. HRGF nanoparticles showed improved in vivo cancer-targeting ability compared with HRG nanoparticles without FA. In vitro drug release profiles revealed that doxorubicin (DOX)-loaded HRGF (D@HRGF) nanoparticles showed rapid release under hypoxia conditions than normoxic conditions. In vitro cytotoxicity tests and microscopic observations showed that D@HRGF nanoparticles were more toxic towards hypoxic cells than normoxic cells, and that the release of DOX was more effective in hypoxia than normoxia. In vivo, D@HRGF nanoparticles showed more effective antitumor activity in mice compared with D@HRG and free DOX. Collectively, these results show that HRGF nanoparticles function as an effective drug-delivery system in hypoxic conditions. Moreover, these hypoxia-responsive nanoparticles would be effective not only in cancer, but also in other ischemic diseases.

Protein separation and identification using magnetic beads encoded with surface-enhanced Raman spectroscopy.

This article presents a prototype of a surface-enhanced Raman spectroscopy (SERS)-encoded magnetic bead of 8mum diameter. The core part of the bead is composed of a magnetic nanoparticle (NP)-embedded sulfonated polystyrene bead. The outer part of the bead is embedded with Ag NPs on which labeling molecules generating specific SERS bands are adsorbed. A silica shell is fabricated for further bioconjugation and protection of SERS signaling. Benzenethiol, 4-mercaptotoluene, 2-naphthalenethiol, and 4-aminothiophenol are used as labeling molecules. The magnetic SERS beads are used as substrates for protein sensing and screening with easy handling. As a model application, streptavidin-bound magnetic SERS beads are used to illustrate selective separation in a flow cytometry system, and the screened beads are spectrally recognized by Raman spectroscopy. The proposed magnetic SERS beads are likely to be used as a versatile solid support for protein sensing and screening in multiple assay technology.

Effective Suppression of Oxidative Stress on Living Cells in Hydrogel Particles Containing a Physically Immobilized WS2 Radical Scavenger.

We report a tungsten disulfide (WS2) nanosheet-immobilized hydrogel system that can inhibit oxidative stress on living cells. First, we fabricated a highly stable suspension of WS2 nanosheets as a radical scavenger by enveloping them with the amphiphilic poly(ε-caprolactone)- b-poly(ethylene oxide) copolymer (PCL- b-PEO) during in situ liquid exfoliation in aqueous medium. After the PCL- b-PEO-enveloped WS2 nanosheets were embedded in three types of hydrogel systems, including carrageenan gum/locust bean gum bulk hydrogels, physically cross-linked alginate microparticles, and covalently cross-linked PEG hydrogel microparticles, they retained their characteristic optical properties. Intriguingly, the WS2 nanosheet-immobilized hydrogel particles exhibited sustainable radical scavenging performance without any deterioration in the original activity of the WS2 nanosheets, even after repeated use. This implies that the hydrogen atoms dissociated from the chalcogen of the WS2 nanosheets effectively scavenged free radicals through the hydrogel mesh. Because of this unique behavior, the coexistence of the WS2 nanosheets with living cells in the hydrogel matrix improved cell viability up to 40%, which demonstrates that the WS2 nanosheets can suppress oxidative stress on living cells.

Macroporous polystyrene-supported palladium catalyst containing a bulky N-heterocyclic carbene ligand for Suzuki reaction of aryl chlorides.

Macroporous polystyrene (MPS)-supported 1-mesitylimidazolium chloride resin was prepared by reacting macroporous chloromethyl polystyrene with 1-mesitylimidazole as a supported N-heterocyclic carbene (NHC) precursor for the immobilization of a palladium catalyst. This MPS-supported NHC precursor readily formed a stable complex with Pd(OAc)2, which effectively catalyzed the Suzuki reaction of aryl iodide and bromides at room temperature and even aryl chlorides at elevated temperatures (100 degrees C). This catalyst showed reusability in the Suzuki reaction of aryl bromide.

Coaxial struts and microfractured structures of compressible thermoelectric foams for self-powered pressure sensors.

Long-term operation of wearable pressure sensors to detect body movement requires self-powered human-based energy sources to minimize the need for recharging. Recently, pressure sensors with thermoelectric properties based on conducting polymers have been reported; however, these devices are limited in their ability to simultaneously achieve sufficient power generation and sensitivity of the sensor. In this article, we suggest a coaxial strut structure of poly(styrene-ethylene/butylene-styrene)(SEBS)-poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)-melamine foam (MF) with a fractured microstructure for a highly sensitive, efficient self-powered pressure sensor. In the coaxial struts, the MF core provides a compressible and elastic framework; the intermediate PEDOT:PSS acts as a conductor and a thermoelectric material; and the SEBS shell ensures mechanical stability and resilience to stabilize the brittle PEDOT:PSS layer under high loading conditions. Additionally, by compressing the coaxial foam to 1/20, partial microfracture of PEDOT:PSS occurs only in the SEBS shell; thus, the pressure sensitivity increases significantly while maintaining high conductivity and thermoelectric performance. The coaxial foam was assembled into a wearable TEG to generate 338 nW from the forearms and demonstrate the high sensitivity of pressure sensors without an external power supply.

Protein complexed with chondroitin sulfate in poly(lactide-co-glycolide) microspheres.

Chondroitin sulfate (CsA) is an acidic mucopolysaccharide, which is able to form ionic complexes with positively charged proteins. In this study, a protein-CsA complex was constructed to nano-sized particles. Zeta potential measurements revealed that a CsA-to-protein fraction of greater than 0.1 results in a neutralization of the positive charge on lysozyme (Lys). Based on this preliminary study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring Lys/CsA complexes via the multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of Lys release from the PLGA microspheres evidenced nearly zero-order kinetics, depending on the quantity of CsA. An in vivo fluorescent image of experimental mouse tissue showed that the PLGA microspheres with the Lys/CsA complex had released the entirety of their Lys without no residual amount after 23 days, but microspheres without the complex harbored a great deal of residual Lys, which is attributable to its degradation by acidic PLGA degradates. The tissue reaction evidenced by the PLGA microspheres stabilized with CsA showed minimal foreign body reaction and little configuration of immune cells including neutrophils and macrophages, but the reactions of the PLGA microspheres without CsA were characterized by a relatively elevated inflammation. These results show that CsA is a viable candidate for long-acting micro-particular protein delivery.

Polymeric nanoparticles for protein kinase activity.

Nanoparticles were prepared from poly-ion complexes, possessing both PEI-FITC-(PKA-specific substrate) (kemptide) and PAA-TRITC, which produce intermolecular FRET; the nanoparticles were dissociated by phosphorylation, presented a strong FITC intensity and can be applied to high-throughput screening for large chemical libraries, for drug discovery of kinase inhibitors.

pH- and temperature-sensitive, injectable, biodegradable block copolymer hydrogels as carriers for paclitaxel.

Paclitaxel (PTX) was loaded into synthetic pH/T-sensitive block copolymer (OSM-PCLA-PEG-PCLA-OSM) solution with various concentrations. The phase diagram of PTX-loaded block copolymer solution shifted to lower temperature region compared to net block copolymer because of the salting-out effect of PTX. Release profiles of PTX showed sustained manner regardless of loading amount of PTX. To evaluate anti-tumor effect of PTX-loaded block copolymer, solutions were injected subcutaneously to tumor-bearing mice and TUNEL assay examined. PTX-loaded block copolymer hydrogel for in vivo use showed good anti-tumor effect for 2 weeks and induced strong apoptosis in tumor tissue. Therefore, we conclude OSM-PCLA-PEG-PCLA-OSM block copolymer as an effective injectable carrier of PTX.

Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in vivo.

Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated N-azidoacetyl-d-mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated 'artificial chemical receptors' containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells in vivo after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as 'artificial chemical receptors' that were conjugated to bioorthogonal chemical group-containing liposomes via in vivo click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells.