Methodological validation of sedimentation velocity analytical ultracentrifugation method for Adeno-Associated Virus and collaborative calibration of system suitability substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and High Sedimentation Coefficient Substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF( high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the RSD (relative standard deviation) could be within 5%. Even for empty or partial less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4×1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Due to the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control)laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

Corrigendum: Study of quality of life and its correlated factors in patients after lumbar fusion for lumbar degenerative disc disease.

[This corrects the article DOI: 10.3389/fsurg.2022.939591.].

Vanadium Hexacyanoferrate Prussian Blue Analogs for Aqueous Proton Storage: Excellent Electrochemical Properties and Mechanism Insights.

The significant attraction toward aqueous proton batteries (APBs) is attributable to their expedited kinetics, elevated safety profile, and economical feasibility. Nevertheless, their practical implement is significantly blocked by the unsatisfactory energy density due to the limited cathode materials. Herein, vanadium hexacyanoferrate Prussian blue analog (VOHCF) is introduced as a potentially favorable cathode material for APBs. The findings demonstrate that this VOHCF electrode exhibits a notable reversible capacity of 102.7 mAh g-1 and exceptional cycling stability, with 95.4% capacity retention over 10 000 cycles at 10 A g-1 . It is noteworthy that this is the detailed instance of VOHCF being proposed as a cathode for APBs. Combining the in situ characterization techniques and theoretical simulations, the origins of excellent proton storage performance are revealed as the multiple redox mechanisms with double active centers of ─C≡N group and V═O bond in VOHCF as well as the robust structure stability. A proton full cell with excellent performance is further achieved by coupling the VOHCF cathode and diquinoxalino[2,3-a:2',3'-c] phenazine (HATN) anode, demonstrating the great potential of VOHCF in practical applications. This work could provide fundamental understanding to the development of feasible cathode materials for proton storage device.

Metastatic Pulmonary Desmoplastic Small Round Cell Tumor on FDG PET/CT.

ABSTRACT: A 33-year-old woman presents with cough and hemoptysis for 1 month. Chest CT showed a soft tissue mass in the left upper lobe of the lung. FDG PET/CT showed multiple foci of intense activity not only in the lung but also in the lymph nodes and the bones, which was diagnosed as lung malignancy with metastases. Histopathology revealed desmoplastic small round cell tumor. Our case indicated that, although the incidence is low, desmoplastic small round cell tumor should be considered among differential diagnoses of lung malignancies.

Quality and consistency of clinical practice guideline recommendations for PET/CT and PET: a systematic appraisal.

OBJECTIVES: To systematically appraise the methodologies used for guidelines for positron emission tomography (PET) imaging and to compare the consistency of these recommendations. METHODS: We searched PubMed, EMBASE, four guideline databases, and Google Scholar to identify evidence-based clinical practice guidelines pertaining to the use of PET, PET/computed tomography (CT), or PET/magnetic resonance in routine practice. We assessed the quality of each guideline using the Appraisal of Guidelines for Research and Evaluation II instrument and compared recommendations regarding indications for 18F-fluorodeoxyglucose (FDG) PET/CT. RESULTS: Thirty-five guidelines for PET imaging, published between 2008 and 2021, were included. These guidelines performed well in the domains of scope and purpose (median 80.6%, inter-quartile range [IQR] 77.8-83.3%) and clarity of presentation (median 75%, IQR 69.4-83.3%), but poorly in applicability (median 27.1%, IQR 22.9-37.5%). Recommendations for 48 indications in 13 cancers were compared. Considerable inconsistencies in the direction of whether to support the use of FDG PET/CT were observed in 10 (20.1%) indications pertaining to 8 cancer types: head and neck cancer (treatment response assessment), colorectal cancer (staging in patients with stages I-III disease), esophageal cancer (staging), breast cancer (restaging and treatment response assessment), cervical cancer (staging in patients with stage < IB2 disease and treatment response assessment), ovarian cancer (restaging), pancreatic cancer (diagnosis), and sarcoma (treatment response assessment). CONCLUSIONS: Current guidelines for PET imaging vary in methodological quality and provided considerably inconsistent recommendations. Efforts are needed to improve adherence to guideline development methodologies, to synthesis high-quality evidence, and to adopt standard terminologies. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42020184965. CLINICAL RELEVANCE STATEMENT: Guidelines for PET imaging provide considerably inconsistent recommendations and vary in methodological quality. It is suggested that clinicians be critical of these recommendations when applying them in practice, that guideline developers adopt more rigorous development methodologies, and that researchers prioritize research gaps identified by current guidelines. KEY POINTS: • PET guidelines vary in methodological quality and provided inconsistent recommendations. Efforts are needed to improve methodologies, synthesize high-quality evidence, and standardize terminologies. • Among six domains of methodological quality assessed by the AGREE II tool, guidelines for PET imaging performed well in scope and purpose (median 80.6%, inter-quartile range 77.8-83.3%) and clarity of presentation (75%, 69.4-83.3%), but poorly in applicability (27.1%, 22.9-37.5%). • Among the 48 recommendations (for 13 cancer types) compared, conflicts in the direction of whether to support FDG PET/CT use were observed in 10 (20.1%), for 8 cancer types (i.e., head and neck, colorectal, esophageal, breast, cervical, ovarian, pancreatic, and sarcoma).

Pulmonary Sclerosing Pneumocytoma on 18 F-FDG PET/MRI.

ABSTRACT: Pulmonary sclerosing pneumocytoma is a rare benign neoplasm. Owing to the low incidence, its radiographic features on 18 F-FDG PET/MRI are not well-known. Herein, we described findings of pulmonary sclerosing pneumocytoma on 18 F-FDG PET/MRI in a 52-year-old woman. It showed moderate FDG uptake and hyperintensity signal on both T1WI and T2WI images.

The Antibacterial Effect, Biocompatibility, and Osteogenesis of Vancomycin-Nanodiamond Composite Scaffold for Infected Bone Defects.

Purpose: The repair and treatment of infected bone defects (IBD) is a common challenge faced by orthopedic clinics, medical materials science, and tissue engineering. Methods: Based on the treatment requirements of IBD, we utilized multidisciplinary knowledge from clinical medicine, medical materials science, and tissue engineering to construct a high-efficiency vancomycin sustained-release system with nanodiamond (ND) and prepare a composite scaffold. Its effect on IBD treatment was assessed from materials, cytology, bacteriology, and zoology perspectives. Results: The results demonstrated that the Van-ND-45S5 scaffold exhibited an excellent antibacterial effect, biocompatibility, and osteogenesis in vitro. Moreover, an efficient animal model of IBD was established, and a Van-ND-45S5 scaffold was implanted into the IBD. Radiographic and histological analyses and bone repair-related protein expression, confirmed that the Van-ND-45S5 scaffold had good biocompatibility and osteogenic and anti-infective activities in vivo. Conclusion: Collectively, our findings support that the Van-ND-45S5 scaffold is a promising new material and approach for treating IBD with good antibacterial effects, biocompatibility, and osteogenesis.

Interface and electronic structure engineering induced Prussian blue analogues with ultra-stable capability for aqueous NH4+ storage.

Aqueous ammonium ion batteries (AAIBs) are considered potential energy storage solutions due to their faster kinetics, eco-friendliness, and high safety. Yet, appropriate electrode material for AAIBs is in continual investigation. Here, Prussian blue analogues (PBAs), Na0.73Ni[Fe(CN)6]0.88, are applied by a covalent bond assisted engineering with in situ polyaniline (PANI) polymerization. The synthesized PANI/Na0.73Ni[Fe(CN)6]0.88 hybrid (PNFF) inherited the advantages of the high conductivity of PANI and the stability of PBAs. The content of PANI had an effect on the electrochemical performance of PNFF. When served as cathode for AAIBs, the as-prepared PNFF-60 (PNFF with adjusted PANI content) delivers an enhanced reversible capacity of 92.5 mA h g-1 at 100 mA g-1 after 200 cycles. Even at a high current density of 2000 mA g-1, 95.2% capacity retention (1000 cycles) can be achieved by PNFF-60. The ammonium storage mechanism of PNFF-60 is fully investigated by in situ Raman and ex situ XPS/FTIR analysis. Moreover, an aqueous NH4+ full cell is assembled by coupling the polyimide@MXene (PI@MXene) anode, exhibiting durable cycling stability. This work adds to the understanding of constructing PBAs-based hybrid electrodes for ammonium ion storage devices.

Study of quality of life and its correlated factors in patients after lumbar fusion for lumbar degenerative disc disease.

Background: In the present work, we aimed to explore the correlated factors of quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease (DDD) in China. Methods: A total of 180 patients treated with lumbar fusion were included in the present study. Their general demographic characteristics, Visual Analog Scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, Simplified Coping Style Questionnaire (SCSQ), Social Support Questionnaire (SSQ), and Medical Outcomes Study Short Form 36 (MOS SF-36) were collected and evaluated preoperatively and at 1 year postoperatively. Results: There were significant improvements in scores of VAS, JOA, and quality of life of patients from preoperation to 1-year postoperation after lumbar fusion. Marital status, with or without children, education level, economic pressure, and social support had significant predictive effects on the physical health of patients undergoing lumbar fusion. Marital status, education level, and economic pressure had significant predictive effects on the mental health of patients undergoing lumbar fusion. Conclusions: Factors correlated with the physical health of patients after lumbar fusion included positive coping style, negative coping style, social support, age, education level (high school college), disease duration (5-10), suffering from other diseases (combined with two or more other disease) and the number of surgical segments (double and three or more). Factors correlated with the mental health included negative coping style, social support, age, education level (middle school and high school college) and the number of surgical segments (double and three or more). The results verify that these factors were correlated to the patient's quality of life after lumbar fusion. Emphasizing and selectively intervening these correlated factors can further improve the quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease.

The use of systematic review evidence to support the development of guidelines for positron emission tomography: a cross-sectional survey.

OBJECTIVES: To examine to what degree guidelines for PET and PET/CT used systematic review evidence. METHODS: The latest version of guidelines for PET, PET/CT or PET/MRI published in English in PubMed until December 2019 was analysed in two categories: (1) for indications, if mainly discussing the appropriate use of PET in diverse conditions; (2) for procedures, if providing step-by-step instructions for imaging. We surveyed the general characteristics and the use of systematic review evidence for developing recommendations across all guidelines, and surveyed the citation of evidence for five recommendation topics in guidelines for procedures. RESULTS: Forty-seven guidelines, published between 2004 and 2020, were included. Guidelines for indications were developed mainly on systematic reviews (13 of 19, 68.4%). Among those, 12 (63.2%) reported the level of evidence, 4 (21.1%) reported the strength of recommendations, 3 (15.8%) described external review and 7 (36.8%) involved methodologists. Guidelines for procedures were seldom developed on systematic reviews (1 of 27, 3.7%). Among those, 1 (3.7%) reported the level of evidence, 1 (3.7%) reported the strength of recommendations, 3 (11.1%) described external review and 1 (3.7%) involved methodologists. Systematic review evidence was cited by 2 (7.4%) procedure guidelines per recommendation topic in median. CONCLUSION: The use of systematic review evidence for developing recommendations among PET or PET/CT guidelines was suboptimal. While our survey is an icebreaking attempt to explore a key element (i.e. use of systematic review evidence) for developing nuclear medicine guidelines, assessments of other domains of guideline quality may help capture the entire picture. KEY POINTS: • The use of systematic review evidence for developing recommendations among guidelines for PET or PET/CT was suboptimal. • Only 13 (68.4%) guidelines for indications and 1 (3.7%) guideline for procedures systematically reviewed the literature during guideline development. • For each recommendation topic we examined, only a median of 2 (7.4%) procedure guidelines cited systematic review evidence.

Current status and quality of radiomics studies in lymphoma: a systematic review.

OBJECTIVES: To perform a systematic review regarding the developments in the field of radiomics in lymphoma. To evaluate the quality of included articles by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), the phases classification criteria for image mining studies, and the radiomics quality scoring (RQS) tool. METHODS: We searched for eligible articles in the MEDLINE/PubMed and EMBASE databases using the terms "radiomics", "texture" and "lymphoma". The included studies were divided into two categories: diagnosis-, therapy response- and outcome-related studies. The diagnosis-related studies were evaluated using the QUADAS-2; all studies were evaluated using the phases classification criteria for image mining studies and the RQS tool by two reviewers. RESULTS: Forty-five studies were included; thirteen papers (28.9%) focused on the differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM). Thirty-two (71.1%) studies were classified as discovery science according to the phase classification criteria for image mining studies. The mean RQS score of all studies was 14.2% (ranging from 0.0 to 40.3%), and 23 studies (51.1%) were given a score of < 10%. CONCLUSION: The radiomics features could serve as diagnostic and prognostic indicators in lymphoma. However, the current conclusions should be interpreted with caution due to the suboptimal quality of the studies. In order to introduce radiomics into lymphoma clinical settings, the lesion segmentation and selection, the influence of the pathological pattern and the extraction of multiple modalities and multiple time points features need to be further studied. KEY POINTS: • The radiomics approach may provide useful information for diagnosis, prediction of the therapy response, and outcome of lymphoma. • The quality of published radiomics studies in lymphoma has been suboptimal to date. • More studies are needed to examine lesion selection and segmentation, the influence of pathological patterns, and the extraction of multiple modalities and multiple time point features.

Low-Grade Myofibroblastic Sarcoma Demonstrated on 99mTc-MDP Bone Scan and 18F-FDG PET/CT.

A 24-year-old woman with left hip pain for 4 months was admitted. Radiographs of the left hip showed a radiolucent lesion in the proximal femur. The lesion demonstrated hypointensity on T1-weighted and high intensity on T2-weighted fat saturated images. Tc-MDP bone scan and F-FDG PET/CT illustrated intense radiotracer accumulation at the osteolytic lesion. Postoperative pathology confirmed a low-grade myofibroblastic sarcoma (LGMS). LGMS is a rare neoplasm, which often occurred in the head and neck region. Our case suggested that LGMS should be considered in the differential diagnosis of proximal femur lesion on Tc-MDP bone scan and F-FDG PET/CT.

Application of a modified surgical position in anterior approach for total cervical artificial disc replacement.

BACKGROUND: Total cervical artificial disc replacement (TDR) has been considered a safe and effective alternative surgical treatment for cervical spondylosis and degenerative disc disease that have failed to improve with conservative methods. Positioning the surgical patient is a critical part of the procedure. Appropriate patient positioning is crucial not only for the safety of the patient but also for optimizing surgical exposure, ensuring adequate and safe anesthesia, and allowing the surgeon to operate comfortably during lengthy procedures. The surgical posture is the traditional position used in anterior cervical approach; in general, patients are in a supine position with a pad under their shoulders and a ring-shaped pillow under their head. AIM: To investigate the clinical outcomes of the use of a modified surgical position versus the traditional surgical position in anterior approach for TDR. METHODS: In the modified position group, the patients had a soft pillow under their neck, and their jaw and both shoulders were fixed with wide tape. The analyzed data included intraoperative blood loss, position setting time, total operation time, and perioperative blood pressure and heart rate. RESULTS: Blood pressure and heart rate were not significantly different before and after body positioning in both groups (P > 0.05). Compared with the traditional position group, the modified position group showed a statistically significantly longer position setting time (P < 0.05). However, the total operation time and intraoperative blood loss were significantly reduced in the modified position group compared with the traditional position group (P < 0.05). CONCLUSION: The clinical outcomes indicated that total operation time and intraoperative blood loss were relatively lower in the modified position group than in the traditional position group, thus reducing the risks of surgery while increasing the position setting time. The modified surgical position is a safe and effective method to be used in anterior approach for TDR surgery.

A Nanoemulsion with A Porphyrin Shell for Cancer Theranostics.

A nanoemulsion with a porphyrin shell (NewPS) was created by the self-assembly of porphyrin salt around an oil core. The NewPS system has excellent colloidal stability, is amenable to different porphyrin salts and oils, and is capable of co-loading with chemotherapeutics. The porphyrin salt shell enables porphyrin-dependent optical tunability. The NewPS consisting of pyropheophorbide a mono-salt has a porphyrin shell of ordered J-aggregates, which produced a narrow, red-shifted Q-band with increased absorbance. Upon nanostructure dissociation, the fluorescence and photodynamic reactivity of the porphyrin monomers are restored. The spectrally distinct photoacoustic imaging (at 715 nm by intact NewPS) and fluorescence increase (at 671 nm by disrupted NewPS) allow the monitoring of NewPS accumulation and disruption in mice bearing KB tumors to guide effective photodynamic therapy. Substituting the oil core with Lipiodol affords additional CT contrast, whereas loading paclitaxel into NewPS facilitates drug delivery.

Endoscopic partial closure followed by adequate drainage for treating delayed perforation caused by duodenal endoscopic submucosal dissection: A case report.

RATIONALE: Delayed perforation of duodenal endoscopic submucosal dissection (ESD) was reported to be up to 14.3%. High invasive surgery remains the main treatment for delayed duodenal perforation. PATIENT CONCERNS: A 56-year-old woman presented with abdominal pain and fever at 1st day after ESD for treating a large laterally spreading tumor in the second part of duodenum. DIAGNOSIS: Emergent abdominal computed tomography revealed the presence of duodenal perforation. INTERVENTIONS: Endoscopic purse-string technique was used to partially close the large mucosal defect. Percutaneous endoscopic gastrostomy was conducted for gastric drainage and proximal drainage of the wound. A nasointestinal decompression tube was placed for distal drainage of the wound. OUTCOMES: No further symptoms were noted after 5 days. Both upper gastrointestinal series and endoscopy confirmed the healing of the wound. LESSONS: Partial closure of the mucosal defect followed by adequate drainage can be selected as a preferred choice for management of delayed duodenal perforation. It may also serve as an alternative for prevention of delayed perforation when complete closure of the mucosal defect is technically difficult or impossible.

Impact of Short-Term Exposure of AuNCs on the Gut Microbiota of BALB/c Mice.

The widespread application of nanoparticles causes extensive public concern on their biological safety. However, up to date, few reports have been associated with the impact of metal nanoparticles on gut microbiota in vivo. In this study, gold nanoclusters (AuNCs) were orally administered to BALB/c mice for 7 days, and the dynamic effects of AuNCs on gut microbiota were investigated at 0 h, 4 h, 8 h, 1 d, 3 d and 7 d, respectively. Using high-throughput sequencing of V4-V5 regions of the 16S rRNA gene on the Illumina MiSeq platform, we found that gavage of AuNCs did not significantly change the gut microbiota diversity and community at the initial 3 days. Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres, Tenericutes and Actinobacteria were the six most abundant phylum in the control and AuNCs groups. However, the phylum Proteobacteria was significantly increased by AuNCs at 7 d (P < 0.05). At the genus level, Roseburia were notably decreased while Staphylococcus, Ureaplasma and Methylobacterium were dramatically increased by AuNCs at 7 d (P < 0.05). Taken together, gavage of AuNCs shifted the bacterial composition at 7 d. This is the first research to investigate the toxicity of AuNCs from the perspective of gut microbiota and opens up a new avenue for the safety or toxicity evaluation of AuNCs.

Matrix metallopeptidase 2 targeted delivery of gold nanostars decorated with IR-780 iodide for dual-modal imaging and enhanced photothermal/photodynamic therapy.

Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes (GNS@BSA/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that GNS@BSA/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, GNS@BSA/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of GNS@BSA/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. STATEMENT OF SIGNIFICANCE: We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of GNS@BSA/IR-780 promoted the prepared nanoparticles (GNS@BSA/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the GNS@BSA/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.

Gd3+-Ion-induced carbon-dots self-assembly aggregates loaded with a photosensitizer for enhanced fluorescence/MRI dual imaging and antitumor therapy.

The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy. To reach the balance between an efficient accumulation in a tumor and rapid clearance from the body, herein we report a new multifunctional nanoprobe: photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots (A-C-dots@Ce6). The A-C-dots@Ce6 were assembled from negatively-charged discrete C-dots using Gd3+ ions as a "glue". which also provided another function of in vivo nanoprobe monitoring via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic pH-dependent disassembly and drug-release property. Benefiting from these advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor-bearing mice under laser irradiation and gradual disassembly in the tumor for later body clearance. Therefore, the nanoprobe potentially provides a new strategy to solve the above balance issue, and brightens the future for antitumor monitoring and treatment.

Mimicking Pathogenic Invasion with the Complexes of Au22(SG)18-Engineered Assemblies and Folic Acid.

Biological systems provide the richest spectrum of sophisticated design for materials engineering. We herein provide a paradigm of Au22(SG)18-engineered (SG, glutathione thiolate) and hydrogen bonds engaged assemblies for mimicking capsid protein self-assembly. The water-evaporation-induced self-assembly method allows discrete ultrasmall gold nanoclusters (GNCs) to be self-assembled into super-GNCs assemblies (SGNCs) ranging from nano-, meso- to microscale in water-dimethyl sulfoxide binary solvents in a template-free manner. After removing free and hydration layer water molecules, the formation of SGNCs is engaged by the collective cohesion of hydrogen bonds between glutathione ligands of gradually approaching GNCs. Then, a series of tightly orchestrated cellular events induced by the complexes of Au22(SG)18-engineered assemblies and folic acid are demonstrated to mimic the invasion of eukaryotic cells by pathogens. First, the activation of macropinocytosis mimics the macropinocytic entry used by the pathogens to invade host cells. Then the cytoplasmic vacuolization is a mimicry of vacuolating effects induced by the oligomeric vacuolating toxins secreted by some bacteria. Lastly, the escaping from macropinosomes into cytosol is in a vacuolating toxin's strategy. The findings demonstrate the capabilities of artificial pathogens to emulate the structures and functions of natural pathogens.