Comparison of general and regional anesthesia on short-term complications in patients undergoing total knee arthroplasty: A retrospective study using national health insurance service-national sample cohort.

This retrospective study compared the mortality and short-term complications according to the choice of general anesthesia or regional anesthesia in patients who underwent a total knee arthroplasty (TKA). We searched the Korean National Health Insurance Service National Sample Cohort database to analyze data from patients who received a TKA between January 2002 and December 2015. Before comparing the general and the regional anesthesia groups, the bias was reduced by propensity score matching. After matching, the mortality and complications occurring within 30 days after a TKA were compared between the 2 groups. In the database, 6491 primary TKA cases were identified. Nine hundred forty-three patients (14.5%) had a TKA performed under general anesthesia, and 5548 (85.5%) had a TKA performed under regional anesthesia. After propensity score matching, the data of 1886 patients were analyzed, with 943 patients in each group. There was no significant difference in mortality (0.32% vs 0.00%), transfusion rate (84.52% vs 84.73%, P = .8989), and length of hospital stay (50 vs 53, P = .5391) between the general and regional anesthesia groups. Most of the complications were not significantly different, but the major complications, including myocardial infarction (1.70% vs 0.64%, P = .0414) and acute renal failure (0.85% vs 0.11%, P = .0391), were higher in the general anesthesia group than in the regional anesthesia group. Also, admission to the intensive care unit (8.48% vs 2.33%, P < .0001) and total cost (₩8067, 400 vs ₩7487, 940, P = .0002) were higher in the general anesthesia group than in the regional anesthesia group. Our study found that regional anesthesia for TKA is associated with a decrease in major complications, including myocardial infarction and acute renal failure, and medical costs.

Quarantining: a mentally distressful but physically comfortable experience in South Korea.

OBJECTIVE: Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic. METHODS: HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility. RESULTS: The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, "Depression/Anxiety" deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48-0.80). However, "Pain/Discomfort" and "Mobility" significantly improved (OR = 5.37, 95% CI:3.71-7.78 and OR = 2.05, 95% CI:1.11-3.80, respectively). CONCLUSION: Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.

What Matters for Depression and Anxiety During the COVID-19 Quarantine?: Results of an Online Cross-Sectional Survey in Seoul, South Korea.

Background: Amid the COVID-19 pandemic, quarantine measures are key to containing the spread of the virus. Millions of people have been required to quarantine throughout the pandemic; the quarantine itself is considered detrimental to mental health conditions. Objective: This study aims to investigate the factors associated with depression and anxiety among quarantined people in Seoul, South Korea. Methods: An online cross-sectional survey was administered from October to November 2020 involving people who were living in Seoul, aged 19 years or above, under a 2-week mandatory quarantine. Their mental health status was measured using the Patient Health Questionnares-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Results: Overall, 1,135 respondents were finally included, resulting in a 22.0% response rate. After controlling for potential confounders, variables, such as the "second half of quarantine period" (OR = 1.78 95% CI: 1.10-2.88), "female" (OR = 1.91 95% CI: 1.16-3.16), and "having pre-existing depression" (OR = 8.03 95% CI: 2.96-21.78) were significantly associated with depression while being quarantined. Those with correct knowledge about the rationale behind for the quarantine (OR = 0.39 95% CI: 0.21-0.72), an understanding of quarantine rules (OR = 0.68 95%CI: 0.52-0.91), and those who felt supported by others (OR = 0.74 95% CI: 0.55-0.99) were less likely to develop depression while quarantining. Similarly, anxiety was significantly associated with the second week (OR = 4.18 95% CI: 1.44-12.09), those with an unstable job status (OR = 3.95 95% CI: 1.60-9.79), perceived support (OR = 0.66, 95% CI: 0.45-0.96), and the fear of being infected (OR = 7.22 95% CI: 1.04-49.95). Conclusions: This study highlights the need to develop precautionary measures to prevent depression and anxiety among people undergoing COVID-19 quarantine. In particular, individuals with depression prior to quarantine should be carefully monitored during the quarantine. Further studies with larger populations are needed.

Effects of the non-contact cardiopulmonary resuscitation training using smart technology.

AIMS: Accurate cardiopulmonary resuscitation (CPR) performance is an essential skill for nursing students so they need to learn the skill correctly from the beginning and carry that forward with them into their clinical practice. For the new normal after coronavirus disease 2019 (COVID-19), safe training modules should be developed. This study aimed to develop non-contact CPR training using smart technology for nursing students and to examine its effects, focusing on the accuracy of their performance. The study used a prospective, single-blind, randomized, and controlled trial with repeated measures. METHODS AND RESULTS: The non-contact CPR training with smart technology consisted of a 40-min theoretical online lecture session and an 80-min non-contact practice session with real-time feedback devices and monitoring cameras. Sixty-four nursing students were randomly assigned to either an experimental group (n = 31) using non-contact training or a control group (n = 33) using general training. The accuracy of chest compression and mouth-to-mouth ventilation, and overall performance ability were measured at pretest, right after training, and at a 4-week post-test. The non-contact CPR training significantly increased the accuracy of chest compression (F = 63.57, P < 0.001) and mouth-to-mouth ventilation (F = 33.83, P < 0.001), and the overall performance ability (F = 35.98, P < 0.001) compared to the general CPR training over time. CONCLUSIONS: The non-contact CPR training using smart technology help nursing students develop their techniques by self-adjusting compression depth, rate, release and hand position, and ventilation volume and rate in real time. Nursing students can learn CPR correctly through the training allowing real-time correction in safe learning environments without face-to-face contact.

Depression During COVID-19 Quarantine in South Korea: A Propensity Score-Matched Analysis.

BACKGROUND: Quarantine, a public health measure used to control the coronavirus disease 2019 (COVID-19) pandemic, has been linked to an increased risk of developing adverse psychological sequelae. This study sought to investigate whether quarantining during the COVID-19 pandemic was associated with depression among Koreans. METHODS: Data were obtained from the Seoul COVID-19 Study of Quarantine (SCS-Q) and the 2019 Korea Community Health Survey (KCHS). Using propensity scores estimated based on sociodemographic and health conditions, 919 individuals undergoing quarantine in the SCS-Q were matched with 919 individuals who did not experience quarantine in the 2019 KCHS. Depressive symptoms were measured using the Korean version of the Patient Health Questionnaire-9 (PHQ-9), where major depression is defined as a PHQ-9 score ≥ 10. Logistic regression models were adjusted for sociodemographic and health-related factors. RESULTS: Depression prevalence was higher in quarantined individuals than in the control group (7.8 vs. 3.8%, p < 0.001). Logistic regression analyses revealed that quarantining was associated with higher likelihoods of having major depression [odds ratio (OR) = 2.28, 95% confidence interval (CI): 1.49, 3.51] after adjusting for relevant covariates. LIMITATIONS: Due to the online nature of the SCS-Q, this study included a limited number of elderly participants, limiting the generalizability of the findings to the general Korean population. CONCLUSIONS: The findings suggest that Koreans undergoing COVID-19 quarantine are at higher risk of depression. While further investigation is warranted, public health measures to control infectious disease outbreaks, such as quarantine, would benefit from incorporating strategies to address unintended adverse psychological effects, such as depression.

Complete Genome Sequence of Leuconostoc kimchii Strain NKJ218, Isolated from Homemade Kimchi.

Leuconostoc kimchii strain NKJ218 was isolated from homemade kimchi in South Korea. The whole genome was sequenced using the PacBio RS II and Illumina NovoSeq 6000 platforms. Here, we report a genome sequence of strain NKJ218, which consists of a 1.9-Mbp chromosome and three plasmid contigs. A total of 2,005 coding sequences (CDS) were predicted, including 1,881 protein-coding sequences.

Microsecond Scale Vibrational Spectroscopic Imaging by Multiplex Stimulated Raman Scattering Microscopy.

Real-time vibrational spectroscopic imaging is desired for monitoring cellular states and cellular processes in a label-free manner. Raman spectroscopic imaging of highly dynamic systems is inhibited by relatively slow spectral acquisition on millisecond to second scale. Here, we report microsecond scale vibrational spectroscopic imaging by lock-in free parallel detection of spectrally dispersed stimulated Raman scattering signal. Using a homebuilt tuned amplifier array, our method enables Raman spectral acquisition, within the window defined by the broadband pulse, at the speed of 32 microseconds and with close to shot-noise limited detection sensitivity. Incorporated with multivariate curve resolution analysis, our platform allows compositional mapping of lipid droplets in single live cells, observation of intracellular retinoid metabolism, discrimination of fat droplets from protein-rich organelles in Caenorhabditis elegans, spectral detection of fast flowing tumor cells, and monitoring drug diffusion through skin tissue in vivo. The reported technique opens new opportunities for compositional analysis of cellular compartment in a microscope setting and high-throughput spectral profiling of single cells in a flow cytometer setting.

Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness.

Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.

PEG-PDLLA micelle treatment improves axonal function of the corpus callosum following traumatic brain injury.

The initial pathological changes of diffuse axonal injury following traumatic brain injury (TBI) include membrane disruption and loss of ionic homeostasis, which further lead to dysfunction of axonal conduction and axon disconnection. Resealing the axolemma is therefore a potential therapeutic strategy for the early treatment of TBI. Monomethoxy poly (ethylene glycol)-poly (D, L-lactic acid) di-block copolymer micelles (mPEG-PDLLA) have been shown to restore depressed compound action potentials (CAPs) of spinal axons and promote functional recovery after spinal cord injury. Here, we evaluate the effect of the micelles on repairing the injured cortical axons following TBI. Adult mice subjected to controlled cortical impact (CCI) were treated with intravenous injection of the micelles at 0 h or 4 h after injury. Evoked CAPs were recorded from the corpus callosum of coronal cortical slices at 2 days after injury. The CCI caused significant decreases in the amplitudes of two CAP peaks that were respectively generated by the faster myelinated axons and slower unmyelinated axons. Micelle treatment at both 0 h and 4 h after CCI resulted in significant increases in both CAP peak amplitudes. Injection of fluorescent dye-labeled micelles revealed high fluorescent staining in cortical gray and white matters underneath the impact site. Labeling membrane-perforated neurons by injecting a membrane impermeable dye Texas Red-labeled dextran into lateral ventricles at 2 h post-CCI revealed that immediate micelle injection after CCI did not reduce the number of dye-stained cortical neurons and dentate granule cells of the hippocampus, indicating its ineffectiveness in repairing plasma membrane of neuronal somata. We conclude that intravenous administration of mPEG-PDLLA micelles immediately or at 4 h after TBI allows brain penetration via the compromised blood brain-barrier, and thereby improves the function of both myelinated and unmyelinated axons of the corpus callosum.

Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord.

An urgent unmet need exists for early-stage treatment of spinal cord injury (SCI). Currently methylprednisolone is the only therapeutic agent used in clinics, for which the efficacy is controversial and the side effect is well-known. We demonstrated functional restoration of injured spinal cord by self-assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA-GC). Chitosan and ferulic acid are strong neuroprotective agents but their systemic delivery is difficult. Our data has shown a prolonged circulation time of the FA-GC nanoparticles allowing for effective delivery of both chitosan and ferulic acid to the injured site. Furthermore, the nanoparticles were found both in the gray matter and white matter. The in vitro tests demonstrated that nanoparticles protected primary neurons from glutamate-induced excitotoxicity. Using a spinal cord contusion injury model, significant recovery in locomotor function was observed in rats that were intravenously administered nanoparticles at 2 h post injury, as compared to non-improvement by methylprednisolone administration. Histological analysis revealed that FA-GC treatment significantly preserved axons and myelin and also reduced cavity volume, astrogliosis, and inflammatory response at the lesion site. No obvious adverse effects of nanoparticles to other organs were found. The restorative effect of FA-GC presents a promising potential for treating human SCIs.

Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats.

This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2 (EN20(-)) (20 nm) or SiO2 (EN100(-)) 2(100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2 (EN20(-))(20 nm) or SiO2 (EN100(-)) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2 (EN20(-)) and SiO2 (EN100(-)) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex.

A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats.

PURPOSE: The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnO(SM20(-))) NPs in Sprague Dawley rats for 90 days. METHODS: The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. RESULTS: No rats died during the test period. However, ZnO(SM20(-)) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. CONCLUSION: A ZnO(SM20(-)) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.

Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.

FRET imaging reveals different cellular entry routes of self-assembled and disulfide bonded polymeric micelles.

Although nanocarriers hold promise for cancer chemotherapy, their intracellular drug delivery pathways are not fully understood. In particular, the influence of nanocarrier stability on cellular uptake is still uncertain. By physically loading hydrophobic FRET probes, we revealed different intracellular drug delivery routes of self-assembled and disulfide bonded micelles. The self-assembled micelles were structurally dissociated by micelle-membrane interactions, and the hydrophobic probes were distributed on the plasma membrane. Alternatively, intact disulfide bonded micelles carrying hydrophobic probes were internalized into cancer cells via multiple endocytic pathways. Following internalization, disulfide bonded micelles were decomposed in early endosomes by glutathione-mediated disulfide bond reduction, exposing the probes to intracellular organelles.

Blood-stable, tumor-adaptable disulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy.

Although targeted delivery mediated by ligand modified or tumor microenvironment sensitive nanocarriers has been extensively pursued for cancer chemotherapy, the efficiency is still limited by premature drug release after systemic administration. Herein we report a highly blood-stable, tumor-adaptable drug carrier made of disulfide (DS) bonded mPEG-(Cys)(4)-PDLLA micelles. Intravenously injected disulfide bonded micelles stably retained doxorubicin in the bloodstream and efficiently delivered the drug to a tumor, with a 7-fold increase of the drug in the tumor and 1.9-fold decrease in the heart, as compared with self-assembled (SA), non-crosslinked mPEG-PDLLA micelles. In vivo administration of disulfide bonded micelles led to doxorubicin accumulation in cancer cell nuclei, which was not observed after administration of self-assembled micelles. With a doxorubicin dose as low as 2 mg/kg, disulfide bonded micelles almost completely suppressed tumor growth in mice.

Effect of the stability and deformability of self-assembled glycol chitosan nanoparticles on tumor-targeting efficiency.

To evaluate the tumor targeting efficiency of self-assembled polymeric nanoparticles, four glycol chitosan nanoparticles (CNPs) with different degrees of hydrophobic substitution were prepared by coupling 7.5, 12, 23, and 35 wt.% of 5ß-cholanic acid to hydrophilic glycol chitosan polymer (GC). The sizes and zeta-potentials of different CNPs in aqueous condition were not significantly different, but their stability and deformability were greatly dependent upon the degree of substitution (DS) of 5ß-cholanic acid. With an increase in hydrophobicity, CNPs became more stable and rigid, as characterized by SDS-PAGE and filtration tests. To compare with CNPs, linear GC and polystyrene nanoparticles (PSNPs) were employed as controls. In vivo tumor accumulation of Cy5.5-labeled linear GC, polystyrene nanoparticles (PSNPs) and CNPs were monitored in flank tumors and liver tumor-bearing mice models using near-infrared fluorescence (NIRF) imaging systems. CNPs displayed higher tumor accumulation than GC and PSNPs via the enhanced permeability and retention (EPR) effect. Interestingly, CNPs containing 23 wt.% of 5ß-cholanic acid (CNP-23%) showed the highest tumor-targeting efficiency compared to other CNPs. As exemplified in this study, the stability of CNP-23% is better than CNP-7.5% and CNP-12% containing 7.5 wt.% and 12 wt.% of 5ß-cholanic acid, respectively, and the deformability of CNP-23% is better than that of CNP-35% containing 35 wt.% of 5ß-cholanic acid. We proposed that the superior tumor-targeting efficiency of CNP-23% is mainly due to their balanced stability and deformability in vivo. This study demonstrates that the degree of hydrophobic substitution of self-assembled nanoparticles could determine their stability and deformability. Importantly, they were founded to be the key factors which affect their tumor-targeting efficiency in vivo, and so that these factors should be highly considered during developing nanoparticles for tumor-targeted imaging or drug delivery.

In vivo NIRF imaging of tumor targetability of nanosized liposomes in tumor-bearing mice.

To optimize tumor targetability of nanosized liposomes for application as drug carriers, various liposomes are prepared by incorporating different amounts (10, 30, and 50 wt%) of cationic, anionic, and PEGylated lipids into neutral lipid. In vivo near-infrared fluorescence images reveal that PEG-PE/PC liposomes display high tumor accumulation in tumor-bearing mice, while large amounts of DOTAP/PC liposomes are rapidly captured in the liver, resulting in poor tumor accumulation. These results demonstrate that optimization of the surface properties of liposomes is very important for their tumor targetability, and that in vivo imaging techniques are useful in developing and optimizing nanosized liposome-based drug carriers.

In-vivo tumor targeting of pluronic-based nano-carriers.

Pluronic-based nano-carriers including bare forms that were composed of Pluronic F 68(NC(PF 68)) or Pluronic F 127(NC(PF 127)), and chitosan-conjugated forms (Chito-NC(PF 68) or Chito-NC(PF 127)) were prepared by photo-polymerizing two kinds of diacrylated Pluronic (F 68 and F 127) and acrylated chitosan to investigate the effect of chitosan conjugation and their physicochemical characteristics (size and hydrophilicity) of Pluronic-based nano-carriers on the tumor targeting efficiency. All of the nano-carriers were stable in serum-containing media without forming any aggregation and did not show any acute cytotoxicity to both normal (NIH3T3 fibroblast) and tumor (SCC7) cells. Chitosan conjugation did not change their sizes or thermo-sensitive properties of the nano-carriers, but significantly increased their in-vitro cellular uptake compared to the corresponding bare forms. The in-vivo tumor accumulation of these nano-carriers was optically monitored by using Cy5.5-attached nano-carriers in SCC7 tumor-bearing mice. For all cases, local accumulation of the injected nano-carriers in liver was not dominant compared to the tumor site, demonstrating good tumor targeting efficacy of the Pluronic-based nano-carriers. Among different samples, chitosan-conjugated nano-carriers showed much better tumor accumulation than bare forms, and mostly remained up to 72h, implying prolonged blood circulation and more efficient tumor accumulation. Between Chito-NC(PF 68) and Chito-NC(PF 127), Chito-NC(PF 68) showed a little better tumor accumulation and retention, suggesting the difference in Pluronic, thus difference in hydrophilicity and the size of the nano-carriers also might affect the tumor targeting. In contrast, bare nano-carriers were initially accumulated well in tumor, but they were excreted from the tumor site relatively rapidly. Therefore, chitosan-functionalization was very effective for improving the tumor targeting efficacy of Pluronic-based nano-carriers.

Accelerated micellization and aggregation of pluronic micelles by interaction with heparin.

The effect of attractive interaction between heparin and Pluronic co-polymer, two important macromolecules in biomedical applications, on the micellar state of Pluronic co-polymer was characterized. By the addition of heparin, the critical micellization temperature (CMT) of Pluronic solution decreased, indicating that heparin promoted micellization. Also, the Pluronic micelles were associated by the action of heparin, and the degree of aggregation became more pronounced by increasing the heparin amount. The association among Pluronic micelles by heparin enhanced the efficiency of chemical cross-linking of di-acrylated Pluronic solution by photo-polymerization, as well as the physical gelation by micelle packing. Thus, heparin can act as a sensitive modulator of Pluronic micelles in addition to its biological functions.

Tumor targeting chitosan nanoparticles for dual-modality optical/MR cancer imaging.

We report tumor targeting nanoparticles for optical/MR dual imaging based on self-assembled glycol chitosan to be a potential multimodal imaging probe. To develop an optical/MR dual imaging probe, biocompatible and water-soluble glycol chitosan (M(w) = 50 kDa) were chemically modified with 5beta-cholanic acid (CA), resulting in amphiphilic glycol chitosan-5beta-cholanic acid conjugates (GC-CA). For optical imaging near-infrared fluorescence (NIRF) dye, Cy5.5, was conjugated to GC-CA resulting in Cy5-labeled GC-CA conjugates (Cy5.5-GC-CA). Moreover, in order to chelate gadolinium (Gd(III)) in the Cy5.5-GC-CA conjugates, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was directly conjugated in Cy5.5-GC-CA. Finally, the excess GdCl(3) was added to DOTA modified Cy5.5-GC-CA conjugates in distilled water (pH 5.5). The freshly prepared Gd(III) encapsulated Cy5.5-GC-CA conjugates were spontaneously self-assembled into stable Cy5.5 labeled and Gd(III) encapsulated chitosan nanoparticles (Cy5.5-CNP-Gd(III)). The Cy5.5-CNP-Gd(III) was spherical in shape and approximately 350 nm in size. From the cellular experiment, it was demonstrated that Cy5.5-CNP-Gd(III) were efficiently taken up and distributed in cytoplasm (NIRF filter; red). When the Cy5.5-GC-Gd(III) were systemically administrated into the tail vein of tumor-bearing mice, large amounts of nanoparticles were successfully localized within the tumor, which was confirmed by noninvasive near-infrared fluorescence and MR imaging system simultaneously. These results revealed that the dual-modal imaging probe of Cy5.5-CNP-Gd(III) has the potential to be used as an optical/MR dual imaging agent for cancer treatment.