Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.

Inhalation of hydrogen-rich gas before acute exercise alleviates exercise fatigue.

Hydrogen, as an antioxidant, may have the potential to mitigate fatigue and improve selected oxidative stress markers induced by strenuous exercise. This study focused on previously unexplored approach of pre-exercise inhalation of hydrogen-rich gas (HRG). Twenty-four healthy adult men first completed prelaboratories to determine maximum cycling power (Wmax) and maximum cycling time (Tmax). Then they were subjected to ride Tmax at 80% Wmax on cycle ergometers after inhaled HRG or placebo gas (air) for 60-minute in a double-blind, counterbalanced, randomized, and crossover design. The cycling frequency in the fatigue modelling process and the rating of perceived exertion (RPE) at the beginning and end of the ride were recorded. Before gas inhalation and after fatigue modeling, visual analog scale (VAS) for fatigue and counter-movement jump (CMJ) were tested, and blood samples were obtained. The results showed that compared to placebo, HRG inhalation induced significant improvement in VAS, RPE, the cycling frequency in the last 30 seconds, the ability to inhibit hydroxyl radicals, and serum lactate after exercise (p < 0.028), but not in CMJ height and glutathione peroxidase activit. In conclusions, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels.

Iron deposition in subcortical nuclei of Parkinson's disease: A meta-analysis of quantitative iron-sensitive magnetic resonance imaging studies.

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2* and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata (P <0.001) and compacta (P <0.001), SN (P <0.001), red nucleus (RN, P <0.001), globus pallidus (P <0.001), putamen (PUT, P = 0.009), and thalamus (P = 0.046) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT (P <0.001), RN (P = 0.003), SN (P = 0.017), and caudate nucleus (P = 0.027) than MSA patients, and lower iron content in RN (P = 0.001), PUT (P <0.001), globus pallidus (P = 0.004), SN (P = 0.015), and caudate nucleus (P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.84). CONCLUSION: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION: PROSPERO; CRD42022344413.

The ultrasonographic characteristics of female periurethral solid masses.

INTRODUCTION AND HYPOTHESIS: Studies on the imaging of female periurethral masses are sparse, and most are focused on cystic lesions. In this article, we studied female periurethral solid masses and reported their ultrasonographic features. METHODS: Fifteen women with periurethral solid masses pathologically diagnosed between January 2008 and April 2021 were assessed. RESULTS: Each patient had only one mass. The pathological types included urethral caruncle (5 patients), urethral leiomyoma (3 patients), urethral malignant tumor (MT) (3 patients), periurethral spindle tumor (3 patients) and cartilage necrosis of pubic symphysis (PS) (1 patient). On ultrasound, all urethral caruncles were located at the urethral meatus. They were hypoechoic/isoechoic and rich in blood flow signal. Each leiomyoma presented as a well-defined hypoechoic mass with an oval shape. The urethral MT had inhomogeneous/isoechoic echoes, with medium to abundant blood flow signal. The spindle cell tumors had regular/irregular shapes, moderate/high density echogenicity and little/rich blood flow signals. The articular cartilage necrosis of PS was regular in shape, with mixed echogenicity and no blood flow. CONCLUSIONS: Ultrasound imaging is a convenient and useful method to evaluate the morphological characteristics of female periurethral solid masses.

Electroencephalogram-Based Complexity Measures as Predictors of Post-operative Neurocognitive Dysfunction.

Physiologic signals such as the electroencephalogram (EEG) demonstrate irregular behaviors due to the interaction of multiple control processes operating over different time scales. The complexity of this behavior can be quantified using multi-scale entropy (MSE). High physiologic complexity denotes health, and a loss of complexity can predict adverse outcomes. Since postoperative delirium is particularly hard to predict, we investigated whether the complexity of preoperative and intraoperative frontal EEG signals could predict postoperative delirium and its endophenotype, inattention. To calculate MSE, the sample entropy of EEG recordings was computed at different time scales, then plotted against scale; complexity is the total area under the curve. MSE of frontal EEG recordings was computed in 50 patients ≥ age 60 before and during surgery. Average MSE was higher intra-operatively than pre-operatively (p = 0.0003). However, intraoperative EEG MSE was lower than preoperative MSE at smaller scales, but higher at larger scales (interaction p < 0.001), creating a crossover point where, by definition, preoperative, and intraoperative MSE curves met. Overall, EEG complexity was not associated with delirium or attention. In 42/50 patients with single crossover points, the scale at which the intraoperative and preoperative entropy curves crossed showed an inverse relationship with delirium-severity score change (Spearman ρ = -0.31, p = 0.054). Thus, average EEG complexity increases intra-operatively in older adults, but is scale dependent. The scale at which preoperative and intraoperative complexity is equal (i.e., the crossover point) may predict delirium. Future studies should assess whether the crossover point represents changes in neural control mechanisms that predispose patients to postoperative delirium.

Computational Analysis of Naturally Occurring Aristolochic Acid Analogues and Their Biological Sources.

Aristolochic acids are known for nephrotoxicity, and implicated in multiple cancer types such as hepatocellular carcinomas demonstrated by recent studies. Natural products that are analogues to aristolochic acids have been constantly isolated from organisms; a larger chemical space of these compounds and a wider coverage of biological sources should be determined in consideration of the potential hazard of aristolochic acid analogues and the wide distribution of their biological sources in the nature. Therefore, we carried out an in silico research of naturally occurring aristolochic acid analogues and their biological sources, as a supplement to existing studies. The result shows a chemical space of 238 naturally occurring aristolochic acid analogues that are present in 175 species of biological sources including 44 traditional medicines. With the computational estimation for toxicity and the implication in hazard assessment of a biological source with the presence of aristolochic acid analogues, we propose that additional awareness should be raised to the public for avoidance of toxic species, especially those that are used as herbal medicines and easily accessible.

Expression of the erythropoietin receptor in patients with proliferative diabetic retinopathy and its correlation with postoperative visual prognosis.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a leading cause of blindness. This study aimed to analyze the expression of the erythropoietin receptor (EpoR) in patients with PDR and its correlation with postoperative visual prognosis. METHODS: Between May 2016 and May 2017, 89 patients who underwent vitreoretinal surgery (VRS) in Affiliated Hospital of North Sichuan Medical College were enrolled. Among them, 45 patients (52 eyes) with PDR and 44 patients (50 eyes) with retinal vein occlusion (RVO) made up the study group and the control group, respectively. All patients received 25G standard flattened three-channel lens-preserving VRS; all procedures were performed by the same physician. Recovery and change in best corrected visual acuity (BCVA) were observed. Subsequently, the patients were divided into group A (improved vision) and group B (no improvement in vision). The integrated optical density (IOD) value of EpoR expression among the groups were compared. Pearson's correlation analysis was used to analyze the correlation between the IOD values of EpoR and the change in visual acuity after surgery for PDR. RESULTS: The IOD value of EpoR in the study group was higher than that in the control group (P<0.05). The postoperative BCVA of the PDR patients was significantly higher than that before surgery (≥0.1 vs. ≤0.02, P<0.05). Of the 45 PDR patients (52 eyes), 34 patients (39 eyes) had improved visual acuity after surgery (group A), while 11 patients (13 eyes) experienced no improvement (group B). The IOD value of EpoR expression in group B was higher than that in group A (P<0.05). Pearson's correlation analysis showed that the IOD value of EpoR expression were positively correlated with the recovery. CONCLUSIONS: EpoR is expressed at a high level in PDR patients. The expression level of EpoR in the epiretinal membrane of PDR patients is positively correlated with the prognosis of postoperative vision. Therefore, EpoR has promise as a prognostic biomarker and a potential therapeutic target for PDR.

Clinical Value of Differential lncRNA Expressions in Diagnosis of Giant Cell Tumor of Bone and Tumor Recurrence.

BACKGROUND: There is currently no clinical biomarker for the early diagnosis of giant cell tumor of bone. Long-chain non-coding RNAs (lncRNAs) have a wide range of important gene regulatory functions and play an important role in the occurrence and development of various malignant tumors. This study mainly screened the differential expression of lncRNAs in patients with giant cell tumor of bone by gene chip technology, verified the biological function. We tried to establish a reference basis for early diagnosis of tumor and prediction of tumor recurrence. METHODS: From September 2018 to September 2019, we randomly selected 20 cases of primary giant cell tumor of bone and 20 cases of recurrent giant cell tumor of bone, and 20 cases of bone trauma tissue. First, the differential expression of incRNAs in the bone tissue of the patients was evaluated via utilizing gene chip technology. The gene chip was Human LncRNA Array v 3.0 (8 x 60 K) was completed by Shanghai Kangcheng Biotechnology Co., Ltd. The DAVID online analysis platform was used to analyze the differentially expressed genes by GO and KEGG pathways. The target lncRNAs were screened; real-time quantitative PCR (qRT-PCR) was used to verify the relative expression levels of target lncRNAs in bone tissue and serum of three groups of patients. RESULTS: Using gene chip technology screening, fold-change (FC) value > 2.0 was used as standard. A total of 1,254 differentially expressed lncRNAs were detected of which 896 were up-regulated and 358 were down-regulated. Additionally, a total of 106 differentially expressed lncRNAs were detected with FC values > 10.0. Among these, 72 lncRNAs were upregulated and 34 lncRNAs were downregulated. We then selected two lncRNAs with up-regulation and down-regulation with the largest fold difference. qRT-PCR analytical results showcased that the expression of AK124776 in bone tissue and serum of patients in the recurrent group was significantly higher than that of the initial group and the normal group. Conversely, for RP11-160A10.2, the expression level in the recurrent group was significantly lower than that in the initial group, and the normal group was the highest; the difference was statistically significant (p < 0.05). Finally, we used the expression levels of AK124776 and RP11-160A10.2 in each group as the diagnostic indicators. According to the receiver operating curve (ROC), the accuracy of AK¬124776 and RP11-160A10.2 in the diagnosis of giant cell tumor of bone (area under the curve), the AUC was 0.865 and 0.877, respectively; the accuracy of predicting recurrence of giant cell tumor of bone was 0.832 and 0.841, respectively. CONCLUSIONS: The early detection of differential expression of lncRNAs in the serum of patients with giant cell tumor of bone is important for the diagnosis of disease and prediction of recurrence. The establishment of stable expression of lncRNAs and simple and easy detection methods are of great value for guiding clinical application.

Folin-Ciocalteu Assay Inspired Polyoxometalate Nanoclusters as a Renal Clearable Agent for Non-Inflammatory Photothermal Cancer Therapy.

Similar to translated thermal ablative techniques in clinic, the occurrence of cellular necrosis during tumor photothermal therapy (PTT) would induce inflammatory responses that are detrimental to therapeutic outcomes. Inspired by the well-known colorimetric Folin-Ciocalteu assay, monodispersed and renal-clearable tungsten (W)-based polyoxometalate nanoclusters (W-POM NCs, average diameter of around 2.0 nm) were successfully obtained here through a facile redox reaction with natural gallic acid in alkaline aqueous solution. Apart from excellent stability in the form of freeze-dried powder, the as-prepared W-POM NCs occupied considerable biocompatibility toward normal cells/tissues both in vitro and in vivo, since no obvious toxicities were observed by treating female Balb/c mice with concentrated W-POM NCs during the 30 day post-treatment period. More importantly, W-POM NCs exhibited not only considerable near-infrared (NIR) light absorption (coloration effect originated from the existence of electron-trapped W5+) for efficient PTT but also impressive anti-inflammatory ability (eliminating inflammation-related reactive oxygen species by the oxidation of W5+ into W6+ state) to achieve better therapeutic outcomes. Thus, our study pioneers the application of POMs for non-inflammatory PTT with expected safety and efficiency.

Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players.

OBJECTIVE: Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. METHODS: Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. RESULTS: Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. INTERPRETATION: Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-83.

Solid phase microextraction of polycyclic aromatic hydrocarbons by using an etched stainless-steel fiber coated with a covalent organic framework.

A new covalent organic framework (COF) was synthesized by the amide coupling between 1,3,5-tris(4-aminophenyl)benzene and trimesoyl chloride at room temperature. The COF was applied as a steel fiber coating for the solid phase microextraction of polycyclic aromatic hydrocarbons (PAHs) from water samples. The effect of extraction time, salt concentration, and extraction temperature on the efficiency of SPME was optimized by a Box-Behnken design. The PAHs were quantified by gas chromatography with mass spectrometric detection. Figures of merit include (a) a wide linear range (typically from 0.2 ng L-1 to 2 µg L-1), (b) low limits of detection (0.29 to 0.94 ng L-1 at S/N = 3), and (c) high enrichment factors (EFs; 819-2420). Density functional theory was employed to study the interaction between the COF cluster and the PAHs. The results demonstrated that the EFs increase with the enhancement of π stacking interaction. The repeatability (one fiber; n = 5) and reproducibility (fiber to fiber; n = 5), expressed as the relative standard deviations were in the range of 4.3%-8.4% and 8.5-11.0%, respectively. The recoveries of the PAHs from water samples spiked at levels of 20.0 and 100 ng L-1 ranged from 79.0% to 105.0%. Graphical abstract A covalent organic framework prepared from 1,3,5-tris(4-aminophenyl)benzene and trimesoyl chloride (TAPB-TMC-COF) was synthesized and employed as solid phase microextraction (SPME) fiber coating for the extraction of polycyclic aromatic hydrocarbons from water samples prior to gas chromatography (GC) - mass spectrometric (MS) detection.

The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction.

BACKGROUND/OBJECTIVES: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN: Observational prospective cohort. SETTING: Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS: Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS: Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION: INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019.

dl-Menthol Loaded Polypyrrole Nanoparticles as a Controlled Diclofenac Delivery Platform for Sensitizing Cancer Cells to Photothermal Therapy.

Cancer cells with up-regulated intracellular heat shock proteins (HSPs) expression under adverse heat environment during photothermal therapy (PTT) always resulted in inefficient oncotherapy. As the expression of HSPs is an energy-dependent manner, inhibiting the aerobic glycolysis pathway to realize tumor starvation and therefore consequently reducing the production of intratumoral adenosine 5'-triphosphate (ATP) would offer an efficient way for sensitizing cancer cells to PTT. DLM@PPy NPs, a polypyrrole (PPy)-based platform complexing with dl-menthol (DLM), was well-designed and successfully developed here as a near-infrared (NIR) light and thermo responsive drug delivery system. Benefiting from the volatile property of DLM and high photothermal conversion ability of PPy, the as-prepared DLM@PPy NPs could continuously generate bubbles under NIR light illumination, which is good for precisely controlling the release of encapsulated drug and monitoring the whole therapeutic process by ultrasound imaging. By encapsulating diclofenac (DC, an inhibitor of glucose transporter 1 to realizing tumor starvation) to form DC/DLM@PPy NPs, on-demand DC release could be easily achieved by selectively turning on/off the NIR light irradiation. After releasing DC in tumor lesion to reduce the generation of intratumoral ATP, a significant intensified cell-killing efficiency of PTT was observed. Thus, our study has demonstrated the good potential of DLM/PPy NPs as a stimuli-responsive DC delivery system for intensified PTT through inhibiting the aerobic glycolysis of cancer cells.

A Novel Semirigid Ureterorenoscope with Vacuum Suctioning System for Management of Single Proximal Ureteral and Renal Pelvic Stones: An Initial Experience.

INTRODUCTION: A novel semirigid ureterorenoscope, named the Sotn ureterorenoscope, was designed with a vacuum suction system. The present study aimed to evaluate the feasibility and safety of using the Sotn ureterorenoscope to manage single proximal ureteral or renal pelvic stones. PATIENTS AND METHODS: Data were retrospectively collected from consecutive patients treated with a Sotn ureterorenoscope between February 2010 and August 2015 at Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Jiangmen Wuyi Traditional Chinese Medicine Hospital in China. The primary outcome was the primary stone-free rate (SFR) in 1 month. The secondary outcomes were the final SFR and the perioperative complication rate. RESULTS: A total of 386 patients were evaluated, including 240 males and 146 females. The median (interquartile range [IR]) age was 50 (40-59) years. There were 96 and 290 stones located in the renal pelvis and proximal ureter, respectively. The median (IR) operative time and console time for all patients were 40 (30-70) and 20 (12-38) minutes, respectively. The primary overall SFR was 86.5%, whereas the SFRs for stones with a diameter of ≤1, 1 to 2, and 2 to 3 cm were 95.7%, 86.9%, and 69.0%, respectively. Complications occurred in 90 patients (23.3%); these complications were classified as Clavien-Dindo grades 1 to 2 (minor) in 79 (20.5%) patients, and grades 3 to 4 (major) in 11 (2.8%). CONCLUSIONS: The novel semirigid Sotn ureterorenoscope featuring a vacuum suction system is effective and safe for managing proximal ureteral and renal pelvic stones.

A chloroquine-loaded Prussian blue platform with controllable autophagy inhibition for enhanced photothermal therapy.

Insufficient and heterogeneously distributed heat commonly leads to the incomplete elimination and recurrence of tumors. Inspired by the fact that autophagy is essential for cell survival in response to harmful stresses, a near-infrared (NIR) light responsive chloroquine (CQ, a well-known autophagy inhibitor) delivery system, consisting of phase-changing material (1-tetradecanol, PCM) and hollow mesoporous Prussian blue nanoparticles (HMPBs), is reported here to deliver CQ to the tumor region to augment the efficacy of photothermal therapy (PTT). In vitro thermosensitive CQ release assays demonstrated that precise "on-off" release profiles of CQ could be readily manipulated, owing to the excellent photothermal conversion abilities of HMPBs and the solid-to-liquid phase change properties of the PCM under NIR light illumination. Furthermore, targeted autophagy inhibition in cancer cells could remarkably amplify the cell-killing efficiency of PTT, leading to synergistic cancer suppression at mild therapeutic temperatures. Therefore, this work is expected to depict an effective strategy for the design and construction of a thermally responsive CQ delivery platform for modulating autophagy inhibition in tumors to reinforce the efficacy of PTT.

Polyacrylic Acid Functionalized Co0.85Se Nanoparticles: An Ultrasmall pH-Responsive Nanocarrier for Synergistic Photothermal-Chemo Treatment of Cancer.

To surmount the challenges of limited drug penetration and therapeutic resistance in solid tumors, stimuli-responsive nanocarrier-based drug delivery systems (DDSs) with relatively small sizes are inherently favorable for combined treatment of cancerous cells. In this work, poly(acrylic acid) (PAA) functionalized Co0.85Se nanoparticles (PAA-Co0.85Se NPs) were synthesized through an ambient aqueous precipitating approach for synergistic photothermal-chemo treatment of cancer. The obtained PAA-Co0.85Se NPs possess ultrasmall size (8.2 ± 2.6 nm), considerable near-infrared (NIR) light absorption, high photothermal transforming efficiency (45.2%) and low cytotoxicity, all of which are beneficial for localized photothermal ablation of cancer cells. Doxorubicin hydrochloride (DOX·HCl) was then successfully loaded on PAA-Co0.85Se NPs with a loading capacity up to 8.3% to form PAA-Co0.85Se-DOX composites, which exhibited an exciting acidic pH-responsive drug release property due to the protonation of amino groups in DOX and carboxyl groups in PAA molecules. As expected, when HeLa cells were treated with PAA-Co0.85Se-DOX NPs as well as NIR laser irradiation, a significant synergistic cell-killing effect was observed, greatly improving the treatment efficiency. Thus, this work presents novel insight into the design of ultrasmall stimuli-responsive nanocarrier-based DDSs for synergistic photothermal-chemo treatment of cancer cells.