Desmond Liam, Margini Simone, Barchiesi Emilio, Pontrelli Giuseppe, Phan Anh N, Gentile Piergiorgio
School of Engineering, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Architecture, Design and Urban Planning, University of Sassari, Alghero, Italy.
APL Bioeng. 2024 Feb 29;8(1):016113. doi: 10.1063/5.0180831. eCollection 2024 Mar.
Osteosarcoma (OS) is a rare form of primary bone cancer, impacting approximately 3.4 × 10 individuals worldwide each year, primarily afflicting children. Given the limitations of existing cancer therapies, the emergence of nanotheranostic platforms has generated considerable research interest in recent decades. These platforms seamlessly integrate therapeutic potential of drug compounds with the diagnostic capabilities of imaging probes within a single construct. This innovation has opened avenues for enhanced drug delivery to targeted sites while concurrently enabling real-time monitoring of the vehicle's trajectory. In this study, we developed a nanotheranostic system employing the layer-by-layer (LbL) technique on a core containing doxorubicin (DOXO) and in-house synthesized carbon quantum dots. By utilizing chitosan and chondroitin sulfate as polyelectrolytes, we constructed a multilayered coating to encapsulate DOXO and docetaxel, achieving a coordinated co-delivery of both drugs. The LbL-functionalized nanoparticles exhibited an approximate size of 150 nm, manifesting a predominantly uniform and spherical morphology, with an encapsulation efficiency of 48% for both drugs. The presence of seven layers in these systems facilitated controlled drug release over time, as evidenced by release tests. Finally, the impact of the LbL-functionalized nanoparticles was evaluated on U2OS and Saos-2 osteosarcoma cells. The synergistic effect of the two drugs was found to be crucial in inducing cell death, particularly in Saos-2 cells treated with nanoparticles at concentrations higher than 10 g/ml. Transmission electron microscopy analysis confirmed the internalization of the nanoparticles into both cell types through endocytic mechanisms, revealing an underlying mechanism of necrosis-induced cell death.
骨肉瘤（OS）是一种罕见的原发性骨癌，全球每年约有3.4×10人受其影响，主要折磨儿童。鉴于现有癌症治疗方法的局限性，近几十年来，纳米诊疗平台的出现引起了相当大的研究兴趣。这些平台在单个结构中无缝整合了药物化合物的治疗潜力和成像探针的诊断能力。这一创新为增强药物向靶向部位的递送开辟了道路，同时能够实时监测载体的轨迹。在本研究中，我们开发了一种纳米诊疗系统，该系统采用层层（LbL）技术，以含有阿霉素（DOXO）和内部合成的碳量子点的核心为基础。通过使用壳聚糖和硫酸软骨素作为聚电解质，我们构建了多层涂层来包裹DOXO和多西他赛，实现了两种药物的协同共递送。LbL功能化纳米颗粒的尺寸约为150nm，呈现出主要均匀的球形形态，两种药物的包封率均为48%。这些系统中的七层结构促进了药物随时间的可控释放，释放测试证明了这一点。最后，评估了LbL功能化纳米颗粒对U2OS和Saos-2骨肉瘤细胞的影响。发现两种药物的协同作用对于诱导细胞死亡至关重要，特别是在浓度高于10μg/ml的纳米颗粒处理的Saos-2细胞中。透射电子显微镜分析证实了纳米颗粒通过内吞机制内化到两种细胞类型中，揭示了坏死诱导细胞死亡的潜在机制。
