Early diagnosis and treatment of osteoarthritis with a Au@PDA-WL NP nano-probe by photoacoustic imaging.

A photoacoustic imaging (Au@PDA-WL NPs) probe was successfully prepared for monitoring the early degeneration of articular cartilage. WYRGRL immobilized on the surface of Au@PDA NPs could target the collagen II peptide, which is expressed on chondrocytes in vivo and in vitro, and the enrichment of this nano-probe on cartilage tissue further resulted in the localized plasmon resonance coupling effect, inducing an enhancement in photothermal conversion capacity after the formation of aggregates. Besides, the catechol structure in the PDA shell could eliminate ROS to effectively delay the development of osteoarthrosis.

Corrigendum to "Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38MAPK Signaling Pathway".

[This corrects the article DOI: 10.1155/2018/8384576.].

Smart Self-Assembly Amphiphilic Cyclopeptide-Dye for Near-Infrared Window-II Imaging.

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.

Protecting Healthcare Professionals during the COVID-19 Pandemic.

OBJECTIVE: To understand how to implement proactive prevention measures among healthcare professionals for preventing potential nosocomial infection. METHODS: 91 healthcare professionals confirmed with the COVID-19 infection were collected, and clinical characteristics and epidemiological data were evaluated. RESULTS: Among the cases, 77 cases (84.6%) were confirmed by the viral nucleic acid test, and the other 14 cases were diagnosed by the clinical investigation. Ground glass opacity and bilateral shadows distribution were observed in 78 cases (85.6%). 56 cases (61.5%) were admitted into Zhongnan Hospital and subjected to antiviral treatment. 73 of a total of 91 cases (80.2%) with a median incubation period of 3 days (IQR, 2 to 6) reported close contact history with patients with the COVID-19 infection. The most common symptoms at the onset of illness were fever (66 cases, 72.5%) and cough (54 cases, 59.3%). The initial positive rate of the CT scan and RT-PCR assay were 84.6% and 48.4%, respectively (P < 0.01). There were 50 cases occurred during the early stage (before Jan 20, 2020), whereas 41 cases occurred at a late stage (after Jan 20, 2020). In the early stage, the most common route of exposure to COVID-19 was via direct care in the absence of any invasive procedure. By contrast, 37 healthcare professionals infected with COVID-19 in the late stage were confirmed to have been exposed via aerosol-generating procedures. CONCLUSION: Identification of the asymptomatic individuals in healthcare settings and prompt response when a suspicious case is considered may render effective control of the nosocomial infection during this pandemic.

Investigation of the Psychological disorders in the healthcare nurses during a coronavirus disease 2019 outbreak in China.

The first case of atypical pneumonia caused by coronavirus disease 2019 (COVID-19) was reported in Wuhan, China in December 2019. Since then, cases of novel coronavirus-infected pneumonia (NCIP) have been reported throughout China as well as in 25 other countries. With the rapid growth of this global outbreak, psychological disorders or impact among the healthcare nurses caused by the COVID-19 pandemic is of great importance and worth to be evaluated. Here, we aimed to determine the levels of stress and psychological disorders of nurses who provided nursing care during the COVID-19 outbreak. A total of 159 nurses who provided healthcare work for COVID-19 patients were enrolled in our study. The psychological disorders and stress level were assessed via a questionnaire implemented by the mobile app. The results showed that the nurses who worked in the non-critical care ward (general ward in which the invasive medical procedure such as mechanical ventilation is absent) scored significantly higher on the traumatization condition (P < .05) and stress level (P < .01) as well as the impact of event scale -revised level (P < .01) compared with those worked in the critical care ward. In contrast to the previous report, our findings revealed that the future intervention for preventing the mental crisis among the healthcare nurses needs to be focusing on the individuals in the non-critical care ward instead of those in the critical care ward under the spreading of COVID-19.

Ductal Carcinoma In Situ of the Breast: Perspectives on Tumor Subtype and Treatment.

OBJECTIVE: To evaluate ductal carcinoma in situ (DCIS) characteristics and the effect of different treatment strategies. Patients and Methods. Using data with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2014, the study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM). RESULTS: A total of 3415 patients with DCIS were eligible. Compared with HoR+/HER- subgroup, patients with triple-negative (TN) and HoR-/HER+ were commonly higher in grade, larger in size, and tended to receive mastectomy (P < 0.05). The multivariate analysis revealed that patients with TN were more likely to have a poorer OS and show a higher breast cancer-specific mortality compared with the HoR+/HER- subgroup (P < 0.05). Multivariate analysis on the history of local treatment and surgery showed patients receiving breast-conserving surgery (BCS) plus radiotherapy (R) and BCS plus axillary lymph node dissection was likely to improve OS without affecting breast cancer-specific mortality (P < 0.05). CONCLUSION: The results demonstrate that DCIS associated with TN subtype portends poor prognosis. Meanwhile, BCS plus R was a preferable option and resulted in survival rates better than those achieved with mastectomy, and SLNB should be considered as an appropriate assessment of axillary staging in patients with DCIS.

A Revised Surgical Strategy for the Distal Tibiofibular Interosseous Osteochondroma.

Osteochondroma is one of the most common benign bone tumor; however, the surgical treatment still remains a challenge for those that occur at the distal tibiofibular interosseous location. Previously, the transfibular approach has been successfully described, but the potential damage of the syndesmosis would give rise to the instability of the ankle joint and thus may result in the unfavorable long-term outcome. Here, a revised strategy which can protect the syndesmotic complex is introduced. From 2010 to 2017, eleven patients with the distal tibiofibular interosseous osteochondroma who underwent the revised surgery were collected. The distal fibular osteotomy and posterior tibial osteotomy were performed to keep the inferior syndesmosis intact for better stability of the ankle joint. Both the anterior tibiofibular ligaments (AITFL) and posterior tibiofibular ligaments (PITFL) have been preserved successfully, and thus, the stability of the ankle joint has been maintained due to our strategy. The VAS and AOFAS scores were utilized to assess the clinical outcome and function. Postoperatively, all the patients were pain-free and were able to wear the appropriate shoes at the last follow-up. Preoperative and postoperative AOFAS scores were 93.63 ± 6.91 and 47.27 ± 5.27 (P < 0.05), respectively. Moreover, the average VAS score was 1.73 ± 0.27 (compared with preoperative as 7.45 ± 2.15, P < 0.05), demonstrating obvious improvement after the operation. To our best knowledge, this is the first time to perform the resection of the distal tibial interosseous osteochondroma involving the fibula without interrupting the inferior syndesmotic complex especially the AITFL and PITFL. We believe that this strategy may pave a new way for optimized clinical outcome for these patients with distal tibiofibular interosseous osteochondroma. This clinical trial study is registered with number ChiCTR1900024690.

The Assessment of the Reduction Algorithm in the Treatment for "Logsplitter" Injury.

As a rare and exceptional injury with significant syndesmotic disruption, the outcome of Logsplitter injury remains poor and unfavorable. In this study, we retrospectively investigated the relationship between the intraoperative reduction quality and the prognosis such as the posttraumatic osteoarthritis to help surgeons achieve better functional outcomes for this high-energy transsyndesmotic ankle fracture dislocation. From January 2015 to February 2019, 31 patients (average 37.6 ± 9.4 years with 19 male and 12 female) diagnosed with the Logsplitter injury were treated by ORIF procedure and enrolled in our study. Particularly, nine vital radiographic parameters including medial clear space, talocrural angle, superior clear space, tibiofibular clear space, tibiofibular overlap, talar tilt, coin sign, tibial medial malleolus angle, and fibular lateral malleolus angle were measured from a postoperative film (AP and mortise view). Next, we compared the clinical outcome by using range of ankle motion, AOFAS scores, Burwell-Charnley score system, and Kellergen-Lawrence criteria from the patients who obtained the intraoperative anatomical reduction with those who failed. Our results showed that AOFAS score with all the patients was 79.33 ± 5.82 at the final follow-up. 14 (45.1%) of 31 patients were observed with radiographic posttraumatic arthritis of the ankle joint with an average Kellgren-Lawrence score of 1.75 ± 1.6 at final follow-up. Most importantly, our results proved that there were significant differences between the patients eligible for anatomical reduction quality with those who failed with regard to OA rate (33.3% vs. 85.7%, P = 0.003) and AOFAS scores (75.33 ± 6.53 vs. 66.89 ± 4.28, P = 0.037) at the final follow-up. Furthermore, the functional outcome after the operation showed an increased range of motion of the ankle joint of the patients obtained anatomical reduction compared with those who failed (P < 0.05). In this study, the significant discrepancy with regard to the functional outcomes was observed between the acceptable and unacceptable radiographic parameters, indicating that the quality of intraoperative reduction is scientifically significant and thus can be utilized as the major factor to predict the clinical outcomes for Logsplitter injuries. Moreover, this reduction algorithm arising from our study can also be applied to other ankle fractures and dislocation involving syndesmotic complex.

Mfn2 inhibits proliferation and cell-cycle in Hela cells via Ras-NF-κB signal pathway.

BACKGROUND: Mitofusin 2 (Mfn2) is outer membrane protein, as the inhibitor of Ras protein. This study aimed to investigate the effect of Mfn2 on cell proliferation, and cell-cycle in Hela cervical carcinoma cell lines. METHODS: After treated with Adv-mfn2 or Adv-control for 48 h and 60 h, the RNA and protein of Mfn2 in Hela cells were detected by qRT-PCR and western blot. The immunofluorescence assay was performed to observe the expression and sub-location of Mfn2 in Hela cells. The flow cytometry was performed to detect the cell cycle of Hela cells, while western blots were performed to observe the Ras-NF-κB signal pathway. Then, the xenografted cervix carcinoma mouse model was used to confirm the effect of Mfn2 in Hela cells in vivo and the expression of Ras-NF-κB signaling pathway in vivo. RESULTS: In immunofluorescence detection, Mfn2 was located in cytoplasmic, not in the nucleus. In addition, Mfn2 inhibited cell proliferation of Hela cells through reducing PCNA protein expression. Mfn2 induced arrest in G0/G1 phase of the cell cycle in Hela cells. Meanwhile, Mfn2 reduced Cyclin D1 protein expression. Moreover, Mfn2 decreased the Ras signal pathway proteins such as Myc, NF-κB p65, STAT3 in a dose-dependent manner. Then, the in vivo experiment also confirmed that Mfn2 could inhibit the tumor growth, and depress the Cyclin D1, Ras, Myc, NF-κB p65, Erk1/2 and mTOR protein expression. CONCLUSIONS: Mfn2 could significantly inhibit cell proliferation in Hela cells. It might be acted as an potential anti-cancer target through inducing cell cycle arrest in human cervical carcinoma cells.

Diketopyrrolopyrrole-based semiconducting polymer nanoparticles for in vivo second near-infrared window imaging and image-guided tumor surgery.

A diketopyrrolopyrrole-based semiconducting polymer nanoparticle (PDFT1032) has been developed as a NIR-II (near infrared window II, 1000-1700 nm) fluorescent probe. It shows high photostability, a favorable absorption peak at 809 nm, a large Stokes shift of 223 nm, outstanding biocompatibility and minimal in vivo toxicity. More importantly, the versatile use of PDFT1032 for several important biomedical applications in the NIR-II window has been demonstrated, including the NIR-II optical imaging of tumors on a subcutaneous osteosarcoma model, assessing the vascular embolization therapy of tumors, and NIR-II image-guided orthotopic tumor surgery and sentinel lymph node biopsy (SLNB) with high spatial and temporal resolution. Overall, excellent biocompatibility, favorable hydrophilicity, and desirable chemical and optical properties make the semiconducting polymer nanoparticle PDFT1032 a highly promising NIR-II imaging probe with the potential to be widely applicable in clinical imaging and the surgical treatment of malignancy.

Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway.

It has been suggested that the activation of the p38 mitogen activated protein kinases (MAPKs) signaling pathway plays a significant role in the progression of OA by leading to the overexpression of proinflammatory cytokines, chemokines, and signaling enzymes in human osteoarthritis chondrocytes. However, most p38 MAPK inhibitors applied for OA have been thought to be limited due to their potential long-term toxicities. Geniposide (GE), an iridoid glycoside purified from the fruit of the herb, has been widely used in traditional medicine for the treatment of a variety of chronic inflammatory diseases. In this study, we evaluated the inhibition effect of geniposide on the inflammatory progression of the surgically induced osteoarthritis and whether the protective effect of geniposide on OA is related to the inhibition of the p38 MAPK signaling pathway. In vitro, geniposide attenuated the expression of inflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), and nitric oxide (NO) production as well as matrix metalloproteinase- (MMP-) 13 in chondrocytes isolated from surgically induced rabbit osteoarthritis model. Additionally, geniposide markedly suppressed the expression of IL-1, TNF-α, NO, and MMP-13 in the synovial fluid from the rabbits with osteoarthritis. More importantly, our results clearly demonstrated that the inhibitory effect of geniposide on surgery-induced expression of inflammatory mediators in osteoarthritis was closely associated with the suppression of the p38 MAPK signaling pathways. Our study demonstrates that geniposide may have therapeutic potential to serve as an alternative agent for the p38 MAPK inhibition for the treatment of OA due to its inherent features of biological activities and low toxicity as a traditional Chinese medicine.

Dual T1 and T2 weighted magnetic resonance imaging based on Gd3+ loaded bioinspired melanin dots.

In this report, a novel T1/T2 dual modal nanoprobe based on highly efficient and bioinspired melanin dots (M-dots) with directly loading gadolinium (Gd-M-dots) for magnetic resonance imaging (MRI) is described. In vitro and in vivo investigations have revealed that Gd-M-dots showed nontoxicity and good biocompatibilitity. Gd-M-dots relaxivity values on 3 T were determined to be r1 = 23.4 and r2 = 123.3 mM-1 s-1, which were much higher than both Gd-DTPA (r1 = 5.1, r2 = 6.2 mM-1 s-1) and Fe-M-dots (r1 = 1.2, r2 = 2.1 mM-1 s-1). For in vivo MRI, after injection of Gd-M-dots, simultaneous T1 and T2 contrast enhancement have been observed in the MRI of mice abdomen and mice bearing U87MG tumors. Furthermore, all the veins showed high signal intensity on T1-weighted MRI and remained for 2 h. Overall, in vitro and in vivo studies indicate that Gd-M-dot with high r1 relaxivity and r2 relaxivity has high potential to be a promising nanoprobe for MR venography and molecular imaging.

Induction of mesenchymal stem cell differentiation in the absence of soluble inducer for cutaneous wound regeneration by a chitin nanofiber-based hydrogel.

Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been considered to be a promising strategy for wound healing. However, poor viability of engrafted BMSCs and limited capabilities of differentiation into the desired cell types in wounds often hinder its application. Few studies report the induction of BMSC differentiation into the skin regeneration-related cell types using natural biopolymer, e.g. chitin and its derivative. Here we utilized a chitin nanofiber (CNF) hydrogel as a directive cue to induce BMSC differentiation for enhancing cutaneous wound regeneration in the absence of cell-differentiating factors. First, a 'green' fabrication of CNF hydrogels encapsulating green fluorescence protein (GFP)-transfected rat BMSCs was performed via in-situ physical gelation without chemical cross-linking. Without soluble differentiation inducers, CNF hydrogels decreased the expression of BMSC transcription factors (Oct4 and Klf4) and concomitantly induced their differentiation into the angiogenic cells and fibroblasts, which are indispensable for wound regeneration. In vivo, rat full-thickness cutaneous wounds treated with BMSC hydrogel exhibited better viability of the cells than did local BMSC injection-treated wounds. Similar to that of the in vitro result, CNF hydrogels induced BMSCs to differentiate into beneficial cell types, resulting in accelerated wound repair characterized by granulation tissue formation. Our data suggest that three-dimensional CNF hydrogel may not only serve as a 'protection' to improve the viability of exogenous BMSCs, but also provide a functional scaffold capable of enhancing BMSC regenerative potential to promote wound healing. This may help to overcome the current limitations to stem cell therapy that are faced in the field of wound regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

Negative pressure wound therapy: Regulating blood flow perfusion and microvessel maturation through microvascular pericytes.

Negative pressure wound therapy (NPWT) has been demonstrated to accelerate wound healing by promoting angiogenesis. However, whether blood flow perfusion is regulated by microvessel maturation and pericytes following NPWT remains unclear, as well as the exact association between pericytes and collagen type IV. The aim of this study was to investigate the relevant association between blood flow perfusion and microvessel maturation and pericytes following NPWT, and to further explore the underlying molecular mechanisms. We also aimed to investigate the association between pericytes and collagen type IV. For this purpose, we created a rat model of diabetic wounds and microvascular blood flow perfusion was detected using a laser Doppler blood perfusion imager. The expression levels of angiogenin-1, tyrosine phosphorylation of tyrosine kinase receptor-2 (Tie-2), α-smooth muscle actin (α-SMA) and collagen type IV were detected and analyzed through immunohistochemistry, immunofluorescence, RT-qPCR and western blot analysis. The results revealed that NPWT promoted the overexpression of angiogenin-1, Tie-2, α-SMA and collagen type IV, and significantly increased blood flow perfusion coupled with microvessel maturation in the NPWT group at the later stages (7-10 days) of wound healing. Our results suggested that NPWT can preferentially enhance vessel maturation and increase the number of pericytes, thus regulating blood flow perfusion. On the other hand, pericytes and collagen type IV had a mutual interaction, promoting microvessel maturation.

Hierarchical Microspheres Constructed from Chitin Nanofibers Penetrated Hydroxyapatite Crystals for Bone Regeneration.

Chitin exists abundantly in crab and shrimp shells as the template of the minerals, which inspired us to mineralize it for fabricating bone grafting materials. In the present work, chitin nanofibrous microspheres were used as the matrix for in situ synthesis of hydroxyapatite (HA) crystals including microflakes, submicron-needles, and submicron-spheres, which were penetrated by long chitin nanofibers, leading to the hierarchical structure. The shape and size of the HA crystals could be controlled by changing the HA synthesis process. The tight interface adhesion between chitin and HA through the noncovanlent bonds occurred in the composite microspheres, and HAs were homogeneously dispersed and bounded to the chitin nanofibers. In our findings, the inherent biocompatibilities of the both chitin and HA contributed the bone cell adhesion and osteoconduction. Moreover, the chitin microsphere with submicron-needle and submicron-sphere HA crystals remarkably promoted in vitro cell adhesion and in vivo bone healing. It was demonstrated that rabbits with 1.5 cm radius defect were almost cured completely within three months in a growth factor- and cell-free state, as a result of the unique surface microstructure and biocompatibilities of the composite microspheres. The microsphere scaffold displayed excellent biofunctions and an appropriate biodegradability. This work opened up a new avenue to construct natural polymer-based organic-inorganic hybrid microspheres for bone regeneration.

Quantitative photoacoustic imaging for early detection of muscle ischemia injury.

Acute lower extremity ischemia is a limb-and life-threatening problem. The timing of clinical intervention is critical to achieving optimal outcomes. However, there has been a lack of effective techniques capable of evaluating muscle and limb damage. Microcirculatory injury is the initial pathological change during ischemic muscle injury. Here, we performed photoacoustic imaging (PAI) in real time to quantitatively detect the degree of microcirculatory injury of ischemic muscles in a rat model in which Evans blue (EB), which strongly binds to albumin in blood, was used as a nontoxic molecular PA probe. The right lower hind limbs of Sprague-Dawley (SD) rats were subjected to 2 or 3 hours of tourniquet-induced ischemia. Then, PA imaging of the tibialis anterior (TA) muscles in the anterior compartment was performed for 0-24 h after the release of compression. Twenty-four hours after reperfusion, rats were euthanized and examined for pathology, edema and muscle viability. Imaging at 680 nm on rats revealed that there was significant signal enhancement in the TA muscles of the two injury groups compared to the control group, and the 3-h injury group had significantly higher PA signal intensity than the 2-h injury group at each time point. Histopathology results obtained from both the normal and the damaged muscles correlated well with the PAI findings. In conclusion, PA imaging is a promising modality for quantitatively detecting limb and muscle ischemic injury and may pave the road for further clinical application.

Enhancement of Bone-Marrow-Derived Mesenchymal Stem Cell Angiogenic Capacity by NPWT for a Combinatorial Therapy to Promote Wound Healing with Large Defect.

Poor viability of engrafted bone marrow mesenchymal stem cells (BMSCs) often hinders their application for wound healing, and the strategy of how to take full advantage of their angiogenic capacity within wounds still remains unclear. Negative pressure wound therapy (NPWT) has been demonstrated to be effective for enhancing wound healing, especially for the promotion of angiogenesis within wounds. Here we utilized combinatory strategy using the transplantation of BMSCs and NPWT to investigate whether this combinatory therapy could accelerate angiogenesis in wounds. In vitro, after 9-day culture, BMSCs proliferation significantly increased in NPWT group. Furthermore, NPWT induced their differentiation into the angiogenic related cells, which are indispensable for wound angiogenesis. In vivo, rat full-thickness cutaneous wounds treated with BMSCs combined with NPWT exhibited better viability of the cells and enhanced angiogenesis and maturation of functional blood vessels than did local BMSC injection or NPWT alone. Expression of angiogenesis markers (NG2, VEGF, CD31, and α-SMA) was upregulated in wounds treated with combined BMSCs with NPWT. Our data suggest that NPWT may act as an inductive role to enhance BMSCs angiogenic capacity and this combinatorial therapy may serve as a simple but efficient clinical solution for complex wounds with large defects.

Circulating fibrocyte mobilization in negative pressure wound therapy.

Non-healing diabetic wounds are difficult to treat. They also create heavy financial burdens for both patients and society. Negative pressure wound therapy (NPWT) has been adopted to treat intractable wounds and has proved to be effective. However, the mechanisms that underlie the effects of this treatment are not entirely understood. Circulating fibrocytes are unique haematopoietic-derived stem cells that have been reported to play a pivotal role in wound healing. Here, we have investigated the effect of NPWT on fibrocyte mobilization and the role of fibrocyte mobilization in the healing of diabetic wounds during NPWT. We show that the NPWT group exhibited 2.6-fold to 12.1-fold greater numbers of tail vein-injected PKH-26-labelled fibrocytes in the diabetic wound sites compared with the control group. We also demonstrate that the full-thickness skin wounds treated with NPWT exhibit significantly reduced mRNA and protein expression, blood vessel density and proliferating cells when exogenous fibrocyte mobilization is inhibited. We speculate that systemic mobilization of fibrocytes during NPWT may be a mechanism for healing intractable wounds in a diabetic rat model experiment and that enhancement of cell mobilization may represent a potential treatment idea for intractable wound healing across all fields of surgery.

Organic Semiconducting Nanoparticles as Efficient Photoacoustic Agents for Lightening Early Thrombus and Monitoring Thrombolysis in Living Mice.

Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.

Multifunctional biomedical imaging in physiological and pathological conditions using a NIR-II probe.

Compared with imaging in the visible (400 - 650 nm) and near-infrared window I (NIR-I, 650 - 900 nm) regions, imaging in near-infrared window II (NIR-II, 1,000-1,700 nm) is a highly promising in vivo imaging modality with improved resolution and deeper tissue penetration. In this work, a small molecule NIR-II dye,5,5'-(1H,5H-benzo[1,2-c:4,5-c'] bis[1,2,5]thiadiazole)-4,8-diyl)bis(N,N-bis(4-(3-((tert-butyldimethylsilyl)oxy)propyl)phenyl) thiophen-2-amine), has been successfully encapsulated into phospholipid vesicles to prepare a probe CQS1000. Then this novel NIR-II probe has been studied for in vivo multifunctional biological imaging. Our results indicate that the NIR-II vesicle CQS1000 can noninvasively and dynamically visualize and monitor many physiological and pathological conditions of circulatory systems, including lymphatic drainage and routing, angiogenesis of tumor and vascular deformity such as arterial thrombus formation and ischemia with high spatial and temporal resolution. More importantly, by virtue of the favorable half-life of blood circulation of CQS1000, NIR-II imaging is capable of aiding us to accomplish precise resection of tumor such as osteosarcoma, and to accelerate the process of lymph nodes dissection to complete sentinel lymph node biopsy for better decision-making during the tumor surgery. Overall, CQS1000 is a highly promising NIR-II probe for multifunctional biomedical imaging in physiological and pathological conditions, surpassing traditional NIR-I imaging modality and pathologic assessments for clinical diagnosis and treatment.