Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles.

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.

Percutaneous reduction, cannulated screw fixation and calcium sulfate cement grafting assisted by 3D printing technology in the treatment of calcaneal fractures.

BACKGROUND: Percutaneous reduction, cannulated screw fixation and calcium sulfate cement grafting (PR + CSC) for treatment of displaced and intra-articular calcaneal fractures (DIACFs) is a difficult technique, because the minimally invasive treatment has limited exposure and cannot be used to reduce articular surface under direct vision. The goal of this study was to apply 3D printing technology to preoperative planning and surgery of DIACFs, and to evaluate its effectiveness, feasibility and safety in fracture repair. METHODS: We enrolled 81 patients with DIACFs in the study from August 2015 to August 2017. Patients with DIACFs in our hospital were randomly divided into the 3D printing group (40 cases) and the conventional group (41 cases). The operation duration, blood loss volume and the number of fluoroscopy were compared. Radiological results were evaluated using radiographs and functional results were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) score. The complications were also assessed. In addition, we made a questionnaire to verify the usefulness of the 3D printed model for both doctors and patients. RESULTS: The operation duration, blood loss volume and the number of fluoroscopy in 3D printing group were significantly less than that in the conventional group. Besides, 3D printing group achieved significantly better radiological results than conventional group both postoperatively and at the final follow-up except the calcaneal width at the final follow-up. The AOFAS score in the 3D printing group was significantly higher than that in the conventional group. In addition, the questionnaire from doctors and patients exhibited high scores of overall satisfaction of the 3D printed models. As for complications, there was no significant difference among the two groups. CONCLUSION: This study suggested the clinical feasibility of PR + CSC assisted by 3D printing technology in the treatment of DIACFs. LEVEL OF EVIDENCE: II.