Polypyrrole nanoparticles conjugating gadolinium chelates were successfully fabricated for dual‐modal magnetic resonance imaging (MRI) and photoacoustic imaging guided photothermal therapy of cancer, ...from a mixture of pyrrole and pyrrole‐1‐propanoic acid through a facile one‐step aqueous dispersion polymerization, followed by covalent attachment of gadolinium chelate, using polyethylene glycol as a linker. The obtained PEGylated polypyrrole nanoparticles conjugating gadolinium chelates (Gd‐PEG‐PPy NPs), sized around around 70 nm, exhibited a high T1 relaxivity coefficient of 10.61 L mm−1 s−1, more than twice as high as that of the relating free Gd3+ complex (4.2 L mm–1 s−1). After 24 h intravenous injection of Gd‐PEG‐PPy NPs, the tumor sites exhibited obvious enhancement in both T1‐weighted MRI intensity and photoacoustic signal compared with that before injection, indicating the efficient accumulation of Gd‐PEG‐PPy NPs due to the introduction of the PEG layer onto the particle surface. In addition, tumor growth could be effectively inhibited after treatment with Gd‐PEG‐PPy NPs in combination with near‐infrared laser irradiation. The passive targeting and high MRI/photoacoustic contrast capability of Gd‐PEG‐PPy NPs are quite favorable for precise cancer diagnosing and locating the tumor site to guide the external laser irradiation for photothermal ablation of tumors without damaging the surrounding healthy tissues. Therefore, Gd‐PEG‐PPy NPs may assist in better monitoring the therapeutic process, and contribute to developing more effective “personalized medicine,” showing great potential for cancer diagnosis and therapy.
A theranostic agent with excellent physiological stability, strong NIR absorption, and high magnetization is fabricated from PEGylated polypyrrole nanoparticles conjugating gadolinium chelates (Gd‐PEG‐PPy NPs). The passive targeting and high MRI/photoacoustic contrast capability of Gd‐PEG‐PPy NPs are favorable for precise cancer diagnosing and locating tumor sites to guide external laser irradiation for photothermal ablation of tumors without damaging surrounding healthy tissue.
Shining light on cancer cells: A cerasomal photosensitizer of high stability and loading efficiency was developed by conjugation of a porphyrin molecule to an organoalkoxysilylated lipid followed by ...sol–gel and self‐assembly processes (see picture). This nanoformulation showed intrinsic fluorescence and significant damage to tumor cells under photoirradiation.
Abstract The combination of CT imaging and photoacoustic (PA) imaging represents not only high resolution and ease of forming 3D visual image for locating tissues of interest, but also good soft ...tissue contrast and excellent high sensitivity, which is very beneficial to the precise guidance for photothermal therapy (PTT). The near infrared (NIR) absorbing Au nanostructures take advantages to operate as a CT contrast agent due to high absorption coefficient of X-ray and outstanding biocompatibility, but show obvious deficiency for PA imaging and PTT because of low photostability. Attacking this problem head on, the Au nanoparticles (NPs) were coated with Prussian blue (PB) which is a typical FDA-approved drug in clinic for safe and effective treatment of radioactive exposure. The obtained core/shell NPs of Au@PB NPs of 17.8 ± 2.3 nm were found to be an excellent photoabsorbing agent for both PTT and PA imaging due to high photostability and high molar extinction coefficient in NIR region. Their gold core of 9.1 ± 0.64 nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100 mm3 sized tumors in nude mice could be completely ablated without recurrence. Such versatile nanoparticles integrating effective cancer diagnosis with noninvasive therapy might bring opportunities to future cancer therapy.
Hypoxia is a hostile hallmark of most solid tumors, which often leads to multidrug resistance (MDR) and causes the failure of chemotherapy. Hypoxia also promotes epithelial-mesenchymal transition ...(EMT), leading to acceleration of tumor metastasis. Many chemotherapeutic drugs can further exacerbate hypoxia and thus promote metastasis. Therefore, relieving hypoxia is necessary for chemotherapy to inhibit both MDR and EMT. Herein, highly stable cerasomal perfluorocarbon nanodroplets with an atomic layer of polyorganosiloxane surface and pH-sensitive tumor-targeting peptide (D-vPCs-O
) were fabricated to co-deliver oxygen and therapeutic drug, doxorubicin. High-intensity focused ultrasound (HIFU) was utilized to trigger the co-release of doxorubicin and oxygen and simultaneously enhance ultrasound imaging, therefore achieving imaging-guided drug delivery. Mild-temperature HIFU (M-HIFU) not only triggered oxygen release from nanodroplets but also slightly elevated tumor temperature to accelerate tumor blood flow. The oxygen release and temperature elevation jointly relieved tumor hypoxia and alleviated MDR, which greatly enhanced the drug therapeutic efficacy as compared to clinically used doxorubicin and Doxil. Overall side effects were also largely reduced owing to the ultrastable drug loading of cerasome. The improvement of insufficient chemotherapy and the relief of tumor hypoxia corporately down-regulated TGF-β1, leading to the alleviation of EMT, and therefore significantly inhibited tumor metastasis. When "D-vPCs-O
+ M-HIFU" was utilized as a neoadjuvant chemotherapy, nanodroplets down-regulated heat shock proteins, reducing tumor relapse after the high-temperature HIFU (H-HIFU)-mediated hyperthermia ablation. The chemo-hyperthermia therapy totally eradicated tumors without any relapse or metastasis, providing a promising way to treat the triple-negative breast cancer, which is highly malignant, easily metastatic, and lacks effective treatments.
Hybrid bicelles have been demonstrated to have great potential for hydrophobic drug delivery. Herein, we report a near-infrared light-driven, temperature-sensitive hybrid bicelles co-encapsulating ...hydrophobic doxorubicin (DOX) and indocyanine green (ICG) (DOX/ICG@HBs). Encapsulation of ICG into the lipid bilayer membrane of DOX/ICG@HBs results in higher photostability than free ICG. DOX/ICG@HBs exhibited temperature-regulated drug release behavior and significant photothermal cytotoxicity. After tail vein injection, such discotic nanoparticles of DOX/ICG@HBs were found to accumulate selectively at the tumor site and act as an efficient probe to enhance fluorescence imaging greatly. The in vivo experiments showed that the DOX/ICG@HBs-mediated chemo- and photothermal combination therapy was more cytotoxic to tumor cells than the photothermal treatment or the chemotherapy alone due to the synergistic effect, reducing the occurrence of tumor metastasis. Therefore, DOX/ICG@HBs can act as a powerful nanotheranostic agent for chemo/photothermal therapy of cancer under the guidance of near-infrared fluorescence imaging.
Fixed-wing vertical take-off and landing (VTOL) UAVs have received more and more attention in recent years, because they have the advantages of both fixed-wing UAVs and rotary-wing UAVs. To meet its ...large flight envelope, the VTOL UAV needs accurate measurement of airflow parameters, including angle of attack, sideslip angle and speed of incoming flow, in a larger range of angle of attack. However, the traditional devices for the measurement of airflow parameters are unsuitable for large-angle measurement. In addition, their performance is unsatisfactory when the UAV is at low speed. Therefore, for tail-sitter VTOL UAVs, we used a 5-hole pressure probe to measure the pressure of these holes and transformed the pressure data into the airflow parameters required in the flight process using an artificial neural network (ANN) method. Through a series of comparative experiments, we achieved a high-performance neural network. Through the processing and analysis of wind-tunnel-experiment data, we verified the feasibility of the method proposed in this paper, which can make more accurate estimates of airflow parameters within a certain range.
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•A multi-objective optimization was implemented to design aortic arch stent-graft.•The optimization strategy is effective and efficient.•The optimized stent-graft design has excellent ...flexibility and radial force.•The optimized design was demonstrated against an ideal arch.
Complications of thoracic endovascular aortic repair are closely related to the mechanical properties of implanted stent-grafts. Compared with straight vessels, the complex morphology of aortic arch imposes strict requirements on stent-graft properties. This study designed and verified an aortic stent-graft by optimizing a specially constructed commercial descending stent-graft. The main structural parameters including strut height, strut number, strut radius, wire diameter, and graft thickness were set as the design variables. The essential mechanical properties (flexibility and radial support force) of stent-grafts relevant to the mentioned variables were selected as objective functions. Surrogate model and multi-objective genetic algorithms were adopted to implement the optimization process. Finally, the optimized stent-graft was virtually implanted into an ideal aortic arch to verify its suitability. The optimization was completed after 16 iterations, demonstrating that the optimization method used in this study was efficient. The results showed that the flexibility of the near-optimal stent-graft improved over 50% and the radial support force was extremely close to that of the original design. Compared with the original design, the sealing effect of the optimized stent-graft was significantly improved. The results of this study provide guidelines and a feasible method for designing aortic arch stent-grafts.
Automatic bridge surface defect detection is of wide concern; it can save human resources and improve work efficiency. The object detection algorithm, especially the You Only Look Once (YOLO) series ...of networks, has important potential in real-time object detection because of its fast detection speed, and it provides an efficient and automatic detection method for bridge surface defect detection. Hence, this paper employs an improved YOLOv3 network for detecting bridge surface defects (cracks and exposed rebar) and compares the effects of the advanced YOLOv2, YOLOv3 and faster region-based convolutional neural network (Faster RCNN) in bridge surface defect detection, and then two approaches (transfer learning and data augmentation) are used to improve the YOLOv3. The results confirm that, by combining high- and low-resolution feature images, the YOLOv3 improves the detection effect of the YOLOv2 (using single-resolution feature images); the average precision (AP) value of the improved YOLOv3 (0.9–0.91) is 6–10% higher than that of the YOLOv2 (0.83–0.86). Then, the anti-noise abilities of the YOLOv2 and YOLOv3 are studied by introducing white Gaussian noise, and the YOLOv3 is better than the YOLOv2. Simultaneously, the YOLO series of detectors perform better in detection speed; the detection speed of the improved YOLOv3 (FPS (frames per second) = 23.8) is 103 times that of the Faster RCNN (FPS = 0.23) with comparable mAP values (improved YOLOv3 = 0.91; Faster RCNN = 0.9). It is demonstrated that, in consideration of detection precision and speed, the proposed improved YOLOv3 is a decent detector for fast and real-time bridge defect detection.
Using prestressed carbon fiber reinforced polymers (CFRPs) is a promising technique for strengthening reinforced concrete (RC) structures. This study aimed to investigate the prestress losses and ...flexural behavior of strengthened RC beams under wetting/drying cycling (WDC) in a chloride-containing environment. Two prestress levels (20% and 40%) and two WDC durations (90 and 180 cycles) were considered. The time-dependent prestress loss under WDC was first monitored by fiber bragg grating (FBG) for 90 days, and the composition of the prestress loss was theoretically analyzed. A four-point bending test was conducted on the strengthened beams after the WDC exposure, and the intermediate crack (IC) debonding strain and the ultimate moment of the strengthened beams were analytically evaluated. The results show that although WDC exposure aggravated the time-dependent prestress losses, the maximum time-dependent prestress losses after 90 WDCs were only 1.75%, indicating the effectiveness of the end anchorage system. After WDC exposure, the failure mode of the strengthened beams shifted from CFRP rupture to IC debonding, accompanied by the reduction of cracking and the ultimate load, CFRP utilization, and the increase of the maximum crack width. Besides, the model of Lu et al. and Said and Wu could be applied to the IC debonding strain prediction after the WDC. When the environmental reduction coefficient was incorporated, ACI 440.2 R and CECS-146 resulted in a precise IC debonding strain. The proposed method could accurately predict the ultimate moment of the prestressed FRP-strengthened RC beams with different failure modes after WDC.
•WDC deteriorated interfacial bonding and thus aggravated the time-dependent prestress losses.•WDC reduced the ultimate load and altered the failure modes of prestressed strengthened beams.•An ultimate moment model was established for prestressed strengthened beams after WDC.
In this paper, theranostic nanoparticles (MnP-DOX NPs) were fabricated by conjugating Mn-porphyrin onto the surface of doxorubicin (DOX)-loaded poly(lactic acid) (PLA) nanoparticles (DOX NPs) for ...potential T1 magnetic resonance imaging and pH-sensitive drug delivery. An in vitro drug release study showed that the release rate of DOX from MnP-DOX NPs was slow at neutral pH but accelerated significantly in acidic conditions. It was found that MnP-DOX NPs could be easily internalized by HeLa cells and effectively suppressed the growth of HeLa cells and HT-29 cells due to the accelerated drug release in acidic lysosomal compartments. Magnetic resonance imaging (MRI) scanning analysis demonstrated that MnP-DOX NPs had much higher longitudinal relaxivity in water (r1 value of 27.8mM−1s−1 of Mn3+) than Mn-porphyrin (Mn(III)TPPS3NH2; r1 value of 6.70mM−1s−1 of Mn3+), behaving as an excellent contrast agent for T1-weighted MRI both in vitro and in vivo. In summary, such a smart and promising nanoplatform integrates multiple capabilities for effective cancer diagnosis and therapy.
