Bigham Ashkan, Fasolino Ines, Borsacchi Silvia, Valente Carmen, Calucci Lucia, Turacchio Gabriele, Pannico Marianna, Serrano-Ruiz Manuel, Ambrosio Luigi, Raucci Maria Grazia
Institute of Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), Viale John Fitzgerald Kennedy 54, Mostra d'Oltremare Padiglione 20, 80125, Naples, Italy.
Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Piazzale V. Tecchio 80, 80125, Naples, Italy.
Bioact Mater. 2024 Jan 24;35:99-121. doi: 10.1016/j.bioactmat.2024.01.018. eCollection 2024 May.
Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions . The effects of surfactant and microwave treatment were assessed : the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells , finding that 150 μg mL was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.
最近，“治疗性再生”一词被用于描述能够引发治疗方法并随后修复/再生组织/器官的生物材料。本研究聚焦于一种新型治疗性再生纳米复合材料的设计，该复合材料由两亲性非离子表面活性剂（泊洛沙姆F127）、生物活性玻璃（BG）和黑磷（BP）组成。通过两步合成策略制备了该纳米复合材料，其中包括微波处理，该处理将BP纳米片（BPNS）转化为尺寸为5±2纳米的量子点（BPQD）。评估了表面活性剂和微波处理的效果：表面活性剂使离子在整个复合材料中均匀分布，而微波处理使复合材料化学稳定。BP的存在增强了生物活性并促进了模拟体液中磷酸钙的形成。测试了含BP纳米复合材料对骨肉瘤细胞的固有抗癌活性，发现150μg/mL是阻止SAOS-2细胞增殖的最低浓度，而不含BP的对应物不影响细胞生长速率。此外，评估了凋亡途径并提出了作用机制。应用近红外（NIR）辐射通过热疗对SAOS-2细胞诱导进一步的增殖抑制。评估了裸露的BP纳米材料和纳米复合材料对骨癌、乳腺癌和前列腺癌细胞迁移和侵袭的抑制作用，以确定纳米材料对原发性和继发性骨癌的抗癌潜力。用健康的成骨细胞和人间充质干细胞测试了纳米复合材料的再生行为；掺入BPQD的纳米复合材料显著促进了成骨细胞的增殖并诱导了干细胞的成骨分化。本研究引入了一个新的多功能治疗性再生平台，在同时进行骨癌治疗和再生方面具有广阔的潜力。
