One-year outcomes of deep brain stimulation in refractory Tourette syndrome.

AIM: Deep brain stimulation (DBS) is one option for treating refractory Tourette syndrome (TS); however, it remains unclear which preoperative factors are predictive of DBS outcomes. This study investigated the efficacy of DBS targeting the anteromedial globus pallidus internus and evaluated predisposing factors affecting the outcomes of DBS in a single center in Korea. METHOD: Twenty patients who had undergone DBS for refractory TS were reviewed retrospectively. Tic symptoms were followed up at 3-month intervals for up to 1 year after surgery. The Yale Global Tic Severity Scale was used to evaluate preoperative/postoperative tic symptoms. Scores from the Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were also evaluated. RESULTS: Patients with refractory TS achieved improvement in tic symptoms within 1 year after DBS. Initial responders who achieved a 35% reduction in Yale Global Tic Severity Scale total score within the first 3 months after DBS showed larger treatment effects during 1-year follow-up. Although no clinical or demographic factors were predictive of initial responses, patients with serious self-injurious behaviors tended to show delayed responses. CONCLUSION: This is the first study to our knowledge to report the DBS outcomes of 20 patients with TS in a single center in Asia. Our study supports the efficacy of DBS targeting anteromedial globus pallidus internus in refractory TS with no evident serious adverse events. Initial responses after DBS seem to be a predictor of long-term outcomes after surgery.

Dorsal striatal functional connectivity changes in Internet gaming disorder: A longitudinal magnetic resonance imaging study.

Internet gaming disorder (IGD) is a behavioral addiction involving excessive online game use despite negative psychosocial consequences. Unrestricted online gaming may lead to changes in striatal activity and the relationship between the striatum and other cortical regions. This study investigated structural and functional abnormalities involving the striatum through longitudinal follow-up magnetic resonance imaging (MRI) assessments. Eighteen young males with IGD (mean age: 23.8 ± 2.0 years) and 18 controls (mean age: 23.9 ± 2.7 years) were evaluated. Subjects were reassessed ≥1 year after the first visit (mean follow-up duration: 22.8 ± 6.7 months), using voxel-based morphometry and seed-based resting-state functional connectivity (FC) analyses in seed regions of the dorsal and ventral striatum. Subjects with IGD had smaller gray matter volume (GMV) in the anterior/middle cingulate cortex compared with controls during initial and follow-up assessments. They exhibited decreased FC between the left dorsal putamen and left medial prefrontal cortex (mPFC) compared with controls. They exhibited increased FC strength between the right dorsal putamen and right middle occipital gyrus (MOG) during follow-up. Subjects with IGD showed a significant correlation between changes in the dorsal putamen-MOG FC and gaming time per day. Young males with IGD showed an altered FC pattern in the dorsal striatum during follow-up. FC of the dorsal striatum in IGD increased in the mPFC and decreased in the MOG. These findings showed that IGD was accompanied by weakening of prefrontal control and strengthening of the sensorimotor network, suggesting that uncontrolled gaming may be related with functional neural changes in the dorsal striatum.

Regional Gray Matter Volume Related to High Occupational Stress in Firefighters.

BACKGROUND: Firefighters inevitably encounter emotionally and physically stressful situations at work. Even firefighters without diagnosed post-traumatic stress disorder receive clinical attention because the nature of the profession exposes them to repetitive trauma and high occupational stress. This study investigated gray matter abnormalities related to high occupational stress in firefighters using voxel-based morphometry (VBM) and surface-based morphometry (SBM). METHODS: We assessed 115 subjects (112 males and 3 females) using magnetic resonance imaging and evaluated occupational stress by the Korean Occupational Stress Scale-26 (KOSS-26). Subjects were classified into highly or lowly stressed groups based on the median value of the KOSS-26. RESULTS: In VBM analysis, we found that firefighters with high occupational stress had lower gray matter volume (GMV) in both sides of the insula, the left amygdala, the right medial prefrontal cortex (mPFC), and the anterior cingulate cortex than firefighters with low occupational stress. In SBM analysis based on regions of interest, the GMV of the bilateral insula and right mPFC were also lower in the highly stressed group. Within the highly stressed group, low GMV of the insula was significantly correlated with the length of service (left: r = -0.347, P = 0.009; right: r = -0.333, P = 0.012). CONCLUSION: Our findings suggest that regional GMV abnormalities are related to occupational stress. Regional gray matter abnormalities and related emotional dysregulation may contribute to firefighter susceptibility to burnout.

Application of a Drone Magnetometer System to Military Mine Detection in the Demilitarized Zone.

We propose a magnetometer system fitted on an unmanned aerial vehicle (UAV, or drone) and a data-processing method for detecting metal antipersonnel landmines (M16) in the demilitarized zone (DMZ) in Korea, which is an undeveloped natural environment. The performance of the laser altimeter was improved so that the drone could fly at a low and stable altitude, even in a natural environment with dust and bushes, and a magnetometer was installed on a pendulum to minimize the effects of magnetic noise and vibration from the drone. At a flight altitude of 1 m, the criterion for M16 is 5 nT. Simple low-pass filtering eliminates magnetic swing noise due to pendulum motion, and the moving average method eliminates changes related to the heading of the magnetometer. Magnetic exploration was conducted in an actual mine-removal area near the DMZ in Korea, with nine magnetic anomalies of more than 5 nT detected and a variety of metallic substances found within a 1-m radius of each detection site. The proposed UAV-based landmine detection system is expected to reduce risk to detection personnel and shorten the landmine-detection period by providing accurate scientific information about the detection area prior to military landmine-detection efforts.

Abnormal gray matter volume and impulsivity in young adults with Internet gaming disorder.

Reduced executive control is one of the central components of model on the development and maintenance of Internet gaming disorder (IGD). Among the various executive control problems, high impulsivity has consistently been associated with IGD. We performed voxel-based morphometric analysis with diffeomorphic anatomical registration by using an exponentiated Lie algebra algorithm (DARTEL) to investigate the relationship of gray matter abnormalities to impulsivity in IGD. Thirty-one young male adults whose excessive Internet gaming began in early adolescence, and 30 age-matched male healthy controls were examined. IGD subjects showed smaller gray matter volume (GMV) in brain regions implicated in executive control, such as the anterior cingulate cortex and the supplementary motor area. The GMVs in the anterior cingulate cortex and the supplementary motor area were negatively correlated with self-reporting scales of impulsiveness. IGD subjects also exhibited smaller GMV in lateral prefrontal and parietal cortices comprising the left ventrolateral prefrontal cortex and the left inferior parietal lobule when compared with healthy controls. The GMVs in the left ventrolateral prefrontal cortex were negatively correlated with lifetime usage of Internet gaming. These findings suggest that gray matter abnormalities in areas related to executive control may contribute to high impulsivity of young adults with IGD. Furthermore, alterations in the prefrontal cortex were related with long-term excessive Internet gaming during adolescence.

Calcium-Triggered Pulsatile Delivery of Parathyroid Hormone from Microbeads for Osteoporosis Treatment.

Recombinant human parathyroid hormone 1-34 (rhPTH 1-34) is the most potent anabolic drug recommended for patients with osteoporosis who do not respond to conventional treatment. However, subcutaneous intermittent injection is the only effective regimen due to its unusual action of mechanism. This regimen is inconvenient and is a big hurdle in clinical applications. In this study, we designed polyelectrolyte microbeads that can deliver rhPTH 1-34 in response to Ca2+ concentration, which indicates the osteoporotic status. Dextran photopolymer was synthesized, mixed with anionic monoacrylate, and photopolymerized by passing through capillary microfluidics to obtain the microbeads. The anionic property of microbeads was confirmed by toluidine blue staining. One microbead, loaded with a 1 day dose of rhPTH 1-34 (23.4 ± 0.9 µg), released rhPTH 1-34 in a triggered manner following the addition of Ca2+ ion. In vitro cell study demonstrated that rhPTH 1-34 released in a pulsatile manner from the microbeads induced osteogenic markers (ALP, RUNX2, and OPN) and precipitated mineral disposition more effectively.

Sophorae Flos extract inhibits RANKL-induced osteoclast differentiation by suppressing the NF-κB/NFATc1 pathway in mouse bone marrow cells.

BACKGROUND: Sophorae Flos (SF) is a composite of flowers and buds of Styphnolobium japonicum (L.) Schott and has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. Previous studies reported that SF possesses anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities. However, the effect of SF in bone resorption has not been studies. In this study, we examined the potential of SF extract (SFE) to inhibit receptor activator of NF-κB ligand (RANKL) -induced osteoclast differentiation in cultured mouse-derived bone marrow macrophages (BMMs). METHODS: BMMs, that act as osteoclast precursors, were cultured with M-CSF (50 ng/ml) and RANKL (100 ng/ml) for 4 days to generate osteoclasts. Osteoclast differentiation was measured by tartrate-resistant acidic phosphatase (TRAP) staining and the TRAP solution assay. Osteoclast differentiation marker genes were analyzed by the quantitative real-time polymerase chain reaction analysis. RANKLs signaling pathways were confirmed through western blotting. RESULTS: SFE significantly decreased osteoclast differentiation in a dose-dependent manner. SFE inhibited RANKL-induced osteoclastogenesis by suppressing NF-κB activation. By contrast, SFE did not affect phospholipase C gamma 2 or subsequent cAMP response element binding activation. SFE inhibited the RANKL-induced expression of nuclear factor of activated T cells c1 (NFATc1). CONCLUSIONS: SFE attenuated the RANKL-mediated induction of NF-κB through inhibition of IκBα phosphorylation, which contributed to inhibiting of RANKL-induced osteoclast differentiation through downregulation of NFATc1.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity.

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach.

Carbon Nanotube Yarn-Based Glucose Sensing Artificial Muscle.

Boronic acid (BA), known to be a reversible glucose-sensing material, is conjugated to a nanogel (NG) derived from hyaluronic acid biopolymer and used as a guest material for a carbon multiwalled nanotube (MWNT) yarn. By exploiting the swelling/deswelling of the NG that originates from the internal anionic charge changes resulting from BA binding to glucose, a NG MWNT yarn artificial muscle is obtained that provides reversible torsional actuation that can be used for glucose sensing. This actuator shows a short response time and high sensitivity (in the 5-100 × 10(-3) m range) for monitoring changes in glucose concentration in physiological buffer, without using any additional auxiliary substances or an electrical power source. It may be possible to apply the glucose-sensing MWNT yarn muscles as implantable glucose sensors that automatically release drugs when needed or as an artificial pancreas.

Insulin-sensitizing and beneficial lipid-metabolic effects of the water-soluble melanin complex extracted from Inonotus obliquus.

Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water-soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)-fed obese mice. When the melanin complex was treated to 3T3-L1 adipocytes, insulin-stimulated glucose uptake was increased significantly, and its phosphoinositide 3-kinase-dependent action was proven with wortmannin treatment. Additionally, dose-dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex-treated cells. Adiponectin gene expression in 3T3-L1 cells incubated with melanin complex increased which was corroborated by increased AMP-activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3-L1 culture. Melanin complex-treated 3T3-L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex-treated HF-fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water-soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid-metabolic effects, making it a candidate for promising antidiabetic agent.

Multiple risk-taking behaviors in Korean adolescents and associated factors: 2020 and 2021 Korea youth risk behavior web-based survey.

OBJECTIVE: Despite the negative health impact of multiple risk-taking behaviors (RTBs), there is a lack of understanding of adolescents who are more prone to multiple RTBs. This study aimed to identify sociodemographic, mental, and physical health variables associated with increased susceptibility to multiple RTBs in each sex. METHODS: Cross-sectional data from the 2020 and 2021 Korea Youth Risk Behavior Web-based Survey was used. A total of 106,979 Korean adolescents (55,460 men and 51,519 women) were assessed on five RTBs (alcohol use, smoking, sexual intercourse, illicit substance use, no seat belt wearing). In comparison to no RTB group, odds ratios of the relevant covariate factors were calculated in one RTB or multiple RTBs groups. RESULTS: Male and female adolescents engaging in multiple RTBs were 6.4% and 3.8%, respectively. Increasing age, low subjective socioeconomic status, and living in rural areas were associated with multiple RTBs regardless of sex. All mental health variables except anxiety were associated with multiple RTBs in both sexes. Physical inactivity and obesity were associated with decreased odds of multiple RTBs in both sexes. CONCLUSION: This study identifies diverse factors associated with multiple RTBs of Korean adolescents and demonstrates existing sex differences. Age and mental health status are the most critical factors that distinguish multiple risk-taking groups from those involved in one or no RTB.

No-ozone cold plasma induces apoptosis in human neuroblastoma cell line via increased intracellular reactive oxygen species (ROS).

BACKGROUND: This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis. METHODS: Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected. RESULTS: NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells. CONCLUSION: These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.

Selective targeting of cellular nucleus using positively-charged quantum dots.

Developing highly selective probes for subcellular regions such as nucleus and cytoplamic organelles is of great interest for cellular imaging and high content screening analysis for biology and medicine. Cytoplasmic delivery of QDs has been well-understood, while nuclear delivery of QDs has been a challenge due to the unique structural characteristics of cell nucleus. In this study, we systematically investigated nucleus penetrating properties of small-sized ligand-exchanged QDs with either positive or negative surface charges in the similar size range of hydrodynamic diameter (7-10 nm). We found that the positively-charged QDs efficiently stain the nucleus in fixed HeLa cells as well as label nucleolar compartments in live HeLa cells. In contrast, the negatively charged QDs with the similar size range stain only the cytoplam in either fixed or live cells. The charge-dependent labeling pattern allowed us to simultaneously perform multiplex imaging of nuclues and cytoplasm. This study offers an insight into efficient nuclear delivery of nanoparticles such as QDs of which surface charge and size are critical for intracelllar localization and delivery.

Association of maternal mental health and drinking/smoking with adolescents' mental health based on the Korea National Health and Nutrition Examination Survey.

Introduction: Depression is one of the major concerns in adolescence, with a global prevalence of approximately 5%. Diverse environmental factors can affect the development of depression depending on the individual developmental stage. Methods: Using data from the Korea National Health and Nutrition Examination Survey (KNHANES), we aimed to investigate the association between socioeconomic factors and mental health in a population of non-clinically ill adolescents in Korea totaling 6,261 adolescents aged 12-18 years. Results: Drinking, smoking, stress, depressed mood, suicidal ideation in adolescents, and stress, depressed mood, and suicidal ideation in mothers were identified as factors associated with adolescent depression. In addition to depressed mood and suicidal ideation, the higher perception of stress in mothers was related to higher stress perception, depressed mood, and suicidal ideation in adolescents. The association of adolescents' mental health with fathers' mental health was weaker than that with mothers' mental health. Additionally, increased smoking and drinking were commonly reported in adolescents with higher stress perception, depressed mood, and suicidal ideation. Discussion: We conclude that close monitoring of mental health is required for adolescents with drinking and smoking habits and mothers with mental health problems.

Height and subjective body image are associated with suicide ideation among Korean adolescents.

Introduction: Suicide is the leading cause of death among Korean adolescents. Suicide has been found to be associated with body mass index (BMI), height, and subjective body image among adults, but investigations of these associations among adolescents are limited. Thus, we aimed to examine to what extent suicide ideation is associated with height, BMI, and subjective body image among Korean adolescents. Methods: This study examined the data of 6,261 adolescents, selected from a nationally representative survey. The participants were divided into subgroups by sex, suicide ideation, and subjective body image. Logistic regression analyses were performed to examine the association of suicide ideation with height, BMI, and subjective body image. Results: The proportion of perceived obesity was high in the total sample; the height Z-score was lower for the group with suicide ideation than the group without suicide ideation; the height Z-scores were also lower for female participants with suicide ideation than those female participants without suicide ideation. The proportions of depressed mood, suicide ideation, and suicide attempts were higher among the total sample and female participants with perceived obesity than among those with a normal body image. On logistic regression, perceived obesity was positively associated with suicide ideation even after adjusting for age, height Z-score, weight Z-score, and depressed mood, whereas height Z-score was negatively associated with suicide ideation. These relationships were more prominent among female participants than among male participants. Conclusion: Low height and perceived obesity, not real obesity, are associated with suicide ideation among Korean adolescents. These findings indicate that the need for an integrated approach to growth, body image, and suicide in adolescents is warranted.

Effect of Muscle Energy Technique on Hamstring Flexibility: Systematic Review and Meta-Analysis.

Since 2005, there have been no systematic reviews on the effects of multiple manual therapies, including muscle energy technique (MET), on the hamstrings. Therefore, this systematic review aimed to provide clinical evidence for the effectiveness of the MET on hamstring flexibility. We queried 10 electronic databases (PubMed, EMBASE, The Cochrane Library, KISS, NDSL, KMBASE, KISTI, RISS, Dbpia, and OASIS) up to the end of March 2022. This study only included randomized controlled trials (RCTs) investigating the use of MET for the hamstring. The literature was organized using Endnote. Literature screening and data extraction were conducted by two researchers independently. The methodological quality of the included RCTs was evaluated using the Cochrane risk-of-bias tool 1.0, and the meta-analysis was performed using RevMan 5.4. In total, 949 patients from 19 RCTs were selected according to the inclusion criteria. During active knee extension tests, the efficacy between MET and other manipulations did not significantly differ. For sit and reach tests, MET groups had higher flexibility compared to stretching (MD = 1.69, 95% CI: 0.66 to 2.73, p = 0.001) and no treatment (MD = 2.02, 95% CI: 0.70 to 3.33, p = 0.003) groups. No significant differences were observed in the occurrence of adverse reactions. Overall, we found that MET is more efficacious for improving hamstring flexibility compared to stretching and having no treatment during sit and reach tests because it combines isometric contraction with stretching. Owing to clinical heterogeneity, uncertain risk of bias, and the small number of included studies, further high-quality studies should assess the effectiveness of MET.

Quantum dot-based screening system for discovery of g protein-coupled receptor agonists.

Cellular imaging has emerged as an important tool to unravel biological complexity and to accelerate the drug-discovery process, including cell-based screening, target identification, and mechanism of action studies. Recently, semiconductor nanoparticles known as quantum dots (QDs) have attracted great interest in cellular imaging applications due to their unique photophysical properties such as size, tunable optical property, multiplexing capability, and photostability. Herein, we show that QDs can also be applied to assay development and eventually to high-throughput/content screening (HTS/HCS) for drug discovery. We have synthesized QDs modified with PEG and primary antibodies to be used as fluorescent probes for a cell-based HTS system. The G protein-coupled receptor (GPCR) family is known to be involved in most major diseases. We therefore constructed human osteosarcoma (U2OS) cells that specifically overexpress two types of differently tagged GPCRs: influenza hemagglutinin (HA) peptide-tagged κ-opioid receptors (κ-ORs) and GFP-tagged A3 adenosine receptors (A3AR). In this study, we have demonstrated that 1) anti-HA antibody-conjugated QDs could specifically label HA-tagged κ-ORs, 2) subsequent treatment of QD-tagged GPCR agonists allowed agonist-induced translocation to be monitored in real time, 3) excellent emission spectral properties of QD permitted the simultaneous detection of two GPCRs in one cell, and 4) the robust imaging capabilities of the QD-antibody conjugates could lead to reproducible quantitative data from high-content cellular images. These results suggest that the present QD-based GPCR inhibitor screening system can be a promising platform for further drug screening applications.

Altered resting-state functional connectivity of the dorsal anterior cingulate cortex with intrinsic brain networks in male problematic smartphone users.

The excessive use of smartphones is associated with various medical complications and mental health problems. However, existing research findings on neurobiological mechanisms behind problematic smartphone use are limited. In this study, we investigated functional connectivity in problematic smartphone users, focusing on the default mode network (DMN) and attentional networks. We hypothesized that problematic smartphone users would have alterations in functional connectivity between the DMN and attentional networks and that such alterations would correlate with the severity of problematic smartphone use. This study included 30 problematic smartphone users and 35 non-problematic smartphone users. We carried out group independent component analysis (group ICA) to decompose resting-state functional magnetic resonance imaging (fMRI) data into distinct networks. We examined functional connectivity using seed-to-seed analysis and identified the nodes of networks in group ICA, which we used as region of interest. We identified greater functional connectivity of the dorsal anterior cingulate cortex (dACC) with the ventral attention network (VAN) and with the DMN in problematic smartphone users. In seed-to-seed analysis, problematic smartphone users showed atypical dACC-VAN functional connectivity which correlated with the smartphone addiction proneness scale total scores. Our resting-state fMRI study found greater functional connectivity between the dACC and attentional networks in problematic smartphone users. Our findings suggest that increased bottom-up and interoceptive attentional processing might play an important role in problematic smartphone use.

Enhanced thermodynamic, pharmacokinetic and theranostic properties of polymeric micelles via hydrophobic core-clustering of superparamagnetic iron oxide nanoparticles.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIO) have been applied for decades to design theranostic polymeric micelles for targeted cancer therapy and diagnostic MR imaging. However, the effects of SPIO on the physicochemical, and biological properties of polymeric micelles have not yet been fully elucidated. Therefore, we investigated potential effect of SPIO on the physical and biological properties of theranostic polymeric micelles using representative cancer drug (doxorubicin; Doxo) and polymer carrier (i.e., poly (ethylene glycol)-co-poly(D,L-lactide), PEG-PLA). METHODS: SPIO were synthesized from Fe(acetyl acetonate)3 in an aryl ether. SPIO and Doxo were loaded into the polymeric micelles by a solvent-evaporation method. We observed the effect of SPIO-clustering on drug loading, micelle size, thermodynamic stability, and theranostic property of PEG-PLA polymeric micelles. In addition, cellular uptake behaviors, pharmacokinetic and biodistribution study were performed. RESULTS: SPIO formed hydrophobic geometric cavity in the micelle core and significantly affected the integrity of micelles in terms of micelle size, Doxo loading, critical micelle concentration (CMC) and in vitro dissociation. In vivo pharmacokinetic studies also showed the enhanced Area Under Curve (AUC) and elongated the half-life of Doxo. CONCLUSIONS: Clustered SPIO in micelles largely affects not only MR imaging properties but also biological and physical properties of polymeric micelles.