Among various cancers, pediatric brain tumors represent the most common cancer type in children and the second most common cause of cancer related deaths. Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side effects on patients during chemotherapy, especially for children as their bodies are still under development. These side effects are believed to be due to the lack of a delivery system with high efficacy and targeting selectivity, resulting in serious damages of normal cells. To improve the efficacy and selectivity, the transferrin (Trans) receptor mediated endocytosis can be utilized for drug delivery system design, as transferrin receptors are expressed on the blood brain barrier (BBB) and often over expressed in brain tumor cells. Carbon dots (C-Dots) have recently emerged as benign nanoparticles in biomedical applications owing to their good water solubility, tunable surface functionalities and excellent biocompatibility. The unique characteristics of C-Dots make them promising candidates for drug delivery development. In this study, carbon dots-transferrin-doxorubicin covalent conjugate (C-Dots-Trans-Dox) was synthesized, characterized by different spectroscopic techniques and investigated for the potential application as a drug delivery system for anticancer drug doxorubicin to treat pediatric brain tumors. Our in vitro results demonstrate greater uptake of the C-Dots-Trans-Dox conjugate compared to Dox alone presumably owing to the high levels of transferrin receptors on these tumor cells. Experiment showed that C-Dots-Trans-Dox at 10 nM was significantly more cytotoxic than Dox alone, reducing viability by 14-45%, across multiple pediatric brain tumor cell lines.
Tibial Tuberosity Advancement (TTA) is a surgical technique based on a linear osteotomy that determines a cranial advancement of the tibial tuberosity in patients suffering from cranial cruciate ligament rupture (CCL). The aim is to neutralize the cranial tibial thrust (CTT) and to reach a 90° angle between the patellar tendon and the tibial plateau with a physiological knee extension of 135°. In our study, a Ti6AI4V ELI (Titanium Aluminium Vanadium) titanium scaffold for the Porous TTA, with excellent properties of osteointegration and osteoconduction when subjected to cyclic loading has been adopted. Based on the previous scientific work on an ovine model, the use of this type of porous scaffolds has subverted the previous models. Scaffold production technology is based on direct mechanical manufacturing called Electron Beam Melting (EBM). For this study, 41 dogs, different breeds, medium-large size, weighing between 10 and 80 kg, aged between 1 and 13 years, were enrolled. The inclusion criteria were based on clinical evaluations (different gaits), drawer test and tibial compression, LOAD score (Liverpool Osteoarthritis in Dogs questionnaire), radiographic diagnosis in sedation with a 135° positioning of the joint and baropodometric investigations (Stance Analyzer). The results show that Porous TTA is an excellent method for functional recovery of the knee joint following the partial and total rupture of the CCL.
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