Background Jaw bones are the most common organs to be invaded by oral malignancies, such as oral squamous cell carcinoma (OSCC), because of their special anatomical relationship. Various serious complications, such as pathological fractures and bone pain can significantly decrease the quality of life or even survival outcomes for a patient. Although chemotherapy is a promising strategy for bone invasion treatment, its clinical applications are limited by the lack of tumor-specific targeting and poor permeability in bone tissue. Therefore, it is necessary to develop a smart bone and cancer dual targeting drug delivery platform. Results We designed a dual targeting nano-biomimetic drug delivery vehicle Asp8[H40-TPZ/IR780@(RBC-H)] that has excellent bone and cancer targeting as well as immune escape abilities to treat malignancies in jaw bones. These nanoparticles were camouflaged with a head and neck squamous cell carcinoma WSU-HN6 cell (H) and red blood cell (RBC) hybrid membrane, which were modified by an oligopeptide of eight aspartate acid (Asp8). The spherical morphology and typical core-shell structure of biomimetic nanoparticles were observed by transmission electron microscopy. These nanoparticles exhibited the same surface proteins as those of WSU-HN6 and RBC. Flow cytometry and confocal microscopy showed a greater uptake of the biomimetic nanoparticles when compared to bare H40-PEG nanoparticles. Biodistribution of the nanoparticles in vivo revealed that they were mainly localized in the area of bone invasion by WSU-HN6 cells. Moreover, the Asp8[H40-TPZ/IR780@(RBC-H)] nanoparticles exhibited effective cancer growth inhibition properties when compared to other TPZ or IR780 formulations. Conclusions Asp8[H40-TPZ/IR780@(RBC-H)] has bone targeting, tumor-homing and immune escape abilities, therefore, it is an efficient multi-targeting drug delivery platform for achieving precise anti-cancer therapy during bone invasion. Graphical Abstract
Objective This study investigates the effects of using a twin inclined plane device (TIPD) on the remolding and ultrastructure variation of mandibular condyle in growing rats. Materials and Methods Forty-eight male Wistar rats (six weeks old, body weight of approximately 190–210 g) were divided into experimental group (wearing appliance, n = 32) and control group (no appliance, n = 16). Samples were collected on days 3, 14, 30, and 60. The immunohistochemical analysis for vascular endothelial growth factor (VEGF) and type II collagen was carried out. Tartrate-resistant acid phosphatase (TRAP) reaction was performed to evaluate the osteoclastic activity. Three-dimensional morphometric images were reconstructed for morphometric analysis by microcomputed tomography (micro-CT). The ultrastructure of the condylar surface was observed by scanning electron microscopy (SEM). Results The expression of VEGF significantly increased, while the expression of type II collagen decreased in the experimental group at days 30 and 60. Furthermore, the enhanced osteoclast activity was observed under the subchondral bone, which was highest at day 30, and decreased to the lowest at day 60 in the experimental group. In addition, adaptive subchondral bone remolding in the posterior part of the condyle was observed at day 60 in the experimental group, and the SEM revealed the ultrastructure variations after installation of the TIPD. However, these changes began to reverse after 30 days. Conclusion Condylar tissue changes point to the osteoclastic activity in the posterior region of the condyle. These adaptive changes point to bone resorption in the posterior condyle. Type II collagen and VEGF contribute to the MCC remolding induced by the TIPD. The ultrastructural changes in the posterior condylar area in response to mechanical stresses are recoverable at the initial stage.
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