Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ. Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation. Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX. Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

Glioblastoma-on-a-chip construction and therapeutic applications.

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment in vivo using traditional in vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking in vivo functions of GBM cells. This technology has shown great potential for applications in personalized precision medicine and GBM immunotherapy. In recent years, there have been efforts to construct GBM-on-a-chip models based on microfluidics and bioprinting. A number of research teams have begun to use GBM-on-a-chip models for the investigation of GBM progression mechanisms, drug candidates, and therapeutic approaches. This review first briefly discusses the use of microfluidics and bioprinting technologies for GBM-on-a-chip construction. Second, we classify non-surgical treatments for GBM in pre-clinical research into three categories (chemotherapy, immunotherapy and other therapies) and focus on the use of GBM-on-a-chip in research for each category. Last, we demonstrate that organ-on-a-chip technology in therapeutic field is still in its initial stage and provide future perspectives for research directions in the field.

Radiological classification of meningiomas with hemorrhagic onset and its clinical significance.

Meningiomas are the most common benign intracranial tumors and frequently present with a gradual onset of neurological deficits; conversely, their acute presentation with hemorrhagic onset appears to be a rare event. Nonetheless, as early surgical evacuation is the foundation of treatment, a timely diagnosis of this rare type of intracranial hemorrhage is necessary. The purpose of the present single-center study was to investigate the radiological characteristics and propose a new bleeding classification for guiding the diagnosis and treatment. A total of 19 patients consecutively diagnosed with hemorrhagic meningioma were enrolled in this retrospective study. Intracranial extra-axial mass, tumor-associated hemorrhage and peritumoral brain edema were the three main radiological features of the hemorrhagic meningiomas. The site of tumor-associated hemorrhage included the peritumoral space, subarachnoid space, subdural space, brain parenchyma and/or intratumor region. Based on the anatomical relationship between meningioma and hematoma, the spontaneous hemorrhage stemming from meningiomas was further summarized into three bleeding patterns involving purely intratumoral hemorrhage (type I), purely extratumoral hemorrhage (type II) and combined intra/extratumoral hemorrhage (type III); furthermore, the type III hemorrhage usually came from type I bleeding that extended into the surrounding regions. The symptoms in type I patients were generally mild and early surgery was performed following adequate preoperative evaluations. The symptoms in type II patients were mild in certain cases and moderate to severe in others, so early or emergency surgery was chosen according to the clinical status of the patient. Almost all type III patients had moderate to severe symptoms and these patients usually required emergency surgery. In addition, patients with different bleeding types may have different pathological mechanisms underlying the tumor bleeding. Apart from being convenient for diagnosis, this concise and practical bleeding classification may aid in the selection of the treatment strategy and facilitate the understanding of the associated mechanisms.