Micro-Nanocarriers Based Drug Delivery Technology for Blood-Brain Barrier Crossing and Brain Tumor Targeting Therapy.

The greatest obstacle to using drugs to treat brain tumors is the blood-brain barrier (BBB), making it difficult for conventional drug molecules to enter the brain. Therefore, how to safely and effectively penetrate the BBB to achieve targeted drug delivery to brain tumors has been a challenging research problem. With the intensive research in micro- and nanotechnology in recent years, nano drug-targeted delivery technologies have shown great potential to overcome this challenge, such as inorganic nanocarriers, organic polymer-carriers, liposomes, and biobased carriers, which can be designed in different sizes, shapes, and surface functional groups to enhance their ability to penetrate the BBB and targeted drug delivery for brain tumors. In this review, the composition and overcoming patterns of the BBB are detailed, and then the hot research topics of drug delivery carriers for brain tumors in recent years are summarized, and their mechanisms of action on the BBB and the factors affecting drug delivery are described in detail, and the effectiveness of targeted therapy for brain tumors is evaluated. Finally, the challenges and dilemmas in developing brain tumor drug delivery systems are discussed, which will be promising in the future for targeted drug delivery to brain tumors based on micro-nanocarriers technology.

Dual-modal magnetic resonance and photoacoustic tracking and outcome of transplanted tendon stem cells in the rat rotator cuff injury model.

Stem cells have been used to promote the repair of rotator cuff injury, but their fate after transplantation is not clear. Therefore, contrast agents with good biocompatibility for labeling cell and a reliable technique to track cell are necessary. Here, we developed a micron-sized PLGA/IO MPs to label tendon stem cells (TSCs) and demonstrated that PLGA/IO MPs were safe and efficient for long-term tracking of TSCs by using dual-modal MR and Photoacoustic (PA) imaging both in vitro and in rat rotator cuff injury. Moreover, TSCs improved the repair of injury and the therapeutic effect was not affected by PLGA/IO MPs labeling. We concluded that PLGA/IO particle was a promising dual-modal MR/PA contrast for noninvasive long-term stem cell tracking.

Preliminary study of real-time three-dimensional contrast-enhanced ultrasound of sentinel lymph nodes in breast cancer.

PURPOSE: To investigate the clinical value of real-time three-dimensional contrast-enhanced ultrasound (3D-CEUS) in the detection of sentinel lymph nodes (SLNs) and drainage lymphatics in breast cancer patients. METHOD: The prospective study was performed in women with pathology-confirmed T1/2 breast cancer between June 2016 and December 2017 who underwent sentinel lymph node biopsy and 3D-CEUS. The number, size, location, enhancement pattern of SLNs, and the lymphatic drainage patterns were reviewed. The routes, location of SLNs, and lymph channels (LCs) on the surface were marked. All patients underwent blue dye-guided sentinel lymph node biopsy (SLNB) finally. RESULTS: According to the postoperative pathology findings and the blue dye staining of the lymphatic drainage routes, there are six patterns of lymphatic drainage routes and the coincidence rate of the 3D-CEUS was 97.4%; the sensitivity, specificity, positive predictive value, negative predictive value, the LN detection rate, and the correct diagnosis rate of the 3D-CEUS were 75%, 93.0%, 81.8%, 89.9%, 95.3%, and 87.7%, respectively. CONCLUSION: 3D-CEUS is a new feasible and useful approach to detect the SLNs and LCs. 3D-CEUS can accurately localize the LCs and SLNs and estimate the presence of metastatic lymph nodes. KEY POINTS: • The three-dimensional contrast-enhanced ultrasound can detect the sentinel lymph nodes. • The three-dimensional contrast-enhanced ultrasound can show the stereo direction of sentinel lymph nodes and lymph drainage routes. • The three-dimensional contrast-enhanced ultrasound can accurately localize the LCs and SLNs and estimate the presence of metastatic lymph nodes.

How Pre-operative Sentinel Lymph Node Contrast-Enhanced Ultrasound Helps Intra-operative Sentinel Lymph Node Biopsy in Breast Cancer: Initial Experience.

We aimed to evaluate the value of sentinel lymph node contrast-enhanced ultrasound (SLN-CEUS) and surface tracing for the biopsy of intra-operative sentinel lymph nodes (SLNs). Between June 2015 and December 2017, a total of 453 patients with early invasive breast cancer were recruited. Patients received an intradermal injection of microbubble contrast agent around the areola on the day before surgery. The locations and sizes of lymphatic channels (LCs) and SLNs were marked on the body surface using gentian violet. Then, injection of double blue dye was performed half an hour before surgery. We compared the pathway of LCs and the location of SLNs obtained from SLN-CEUS and blue dye during surgery. Among the 453 patients, the mean numbers of LCs and SLNs detected by SLN-CEUS were 1.42 and 1.72, respectively, and the coincidence rate was 98.2% compared with blue dye during surgery. The median distance from the SLN to skin measured by pre-operative CEUS and blue dye was 1.95 ± 0.69 and 2.03 ± 0.87 cm (p = 0.35). There were three SLN enhancement in our research, including homogeneous enhancement, inhomogeneous enhancement and no enhancement, with the sensitivity, specificity, positive predictive value and negative predictive value of SLN-CEUS for the diagnosis of SLNs being 96.82%, 91.91%, 87.54% and 98.01%, respectively. SLN-CEUS with skin marking can identify the pathway of LCs and the location of the SLN before surgery, measure the distance from the SLN to skin and determine if the SLN is metastatic. SLN-CEUS can be used as an effective complement to the blue dye method.

Quantitative Elastography of Rectal Lesions: The Value ofShear Wave Elastography in Identifying Benign and Malignant Rectal Lesions.

We evaluate the value of shear wave elastography (SWE) in diagnosing benign and malignant rectal lesions. A total of 96 lesions were reviewed in this study; endorectal ultrasound (ERUS) and SWE examinations were performed before surgery in all cases. Elasticity parameters including mean elastographic index (Emean), maximum elastographic index (Emax) and minimum elastographic index (Emin) were analyzed. Correlations between elastographic parameters and histopathological results were studied. Inter-observer and intra-observer agreement was analyzed. Of the 96 rectal lesions, 72 were malignant and 24 were benign. Compared with ERUS, ERUS + SWE had higher sensitivity (93.0% vs. 88.9%), specificity (83.3% vs. 79.2%), positive predictive value (94.4% vs. 92.7%), negative predictive value (80.0% vs. 70.4%) and overall accuracy (90.6% vs. 86.4%). In receiver operating characteristic curve analysis, Emean and Emax had larger areas under the curve: 0.92 and 0.91, respectively. The optimal cutoff value was 61.3 kPa for Emean (sensitivity = 88.9%, specificity = 87.5%) and 63.4 kPa for Emax (sensitivity = 94.4%, specificity = 83.3%). We obtained κ values of 0.83 (95% confidence interval [CI]: 0.72-0.95) for ERUS and 0.90 (95% CI: 0.81-0.99) for ERUS + SWE of differential diagnosis in two observers. The intra-class correlation coefficients for intra-observer variability of stiffness (Emean) in malignant lesions, benign lesions, surrounding normal rectal wall in malignant lesions and surrounding normal rectal wall in benign lesions were 0.91 (95% CI: 0.86-0.94), 0.94 (95% CI: 0.88-0.97), 0.92 (95% CI: 0.88-0.95) and 0.89 (95% CI: 0.77-0.95), respectively. SWE is a promising tool that yields valuable quantitative data additional to that provided by ERUS examination in rectal lesions. The cutoff value 61.3 kPa for Emean may serve as a complementary tool in diagnosis of rectal lesions.

Dual-modal photoacoustic and magnetic resonance tracking of tendon stem cells with PLGA/iron oxide microparticles in vitro.

Reliable cell tracking is essential to understand the fate of stem cells following implantation, and thus promote the clinical application of stem cell therapy. Dual or multiple modal imaging modalities mediated by different types of multifunctional contrast agent are generally needed for efficient cell tracking. Here, we created a new contrast agent-PLGA/iron oxide microparticles (PLGA/IO MPs) and characterized the morphology, structure and function of enhancing both photoacoustic (PA) and magnetic resonance imaging (MRI). Both PA and MRI signal increased with increased Fe concentration of PLGA/IO MPs. Fluorescent staining, Prussian blue staining and transmission electron microscope (TEM) certified that PLGA/IO MPs were successfully encapsulated in the labeled TSCs. The established PLGA/IO MPs demonstrated superior ability of dual-modal PA/MRI tracking of TSCs without cytotoxicity at relatively lower Fe concentrations (50, 100 and 200 µg/mL). The optimal Fe concentration of PLGA/IO MPs was determined to be 100 µg/mL, thus laying a foundation for the further study of dual-modal PA/MRI tracking of TSCs in vivo and promoting the repair of injured tendon.