Battaglini Matteo, Tapeinos Christos, Cavaliere Ivana, Marino Attilio, Ancona Andrea, Garino Nadia, Cauda Valentina, Palazon Francisco, Debellis Doriana, Ciofani Gianni
Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025 Pontedera, Pisa, Italy.
Scuola Superiore Sant'Anna, The Biorobotics Institute, Viale Rinaldo Piaggio 34, 56025 Pontedera, Pisa, Italy.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):670-682. doi: 10.1021/acsbiomaterials.8b01033. Epub 2019 Jan 3.
Neurodegenerative diseases comprise a large group of disorders characterized by a dramatic synaptic connections loss, occurring as a result of neurodegeneration, which is closely related to the overproduction of reactive oxygen and nitrogen species. Currently, the treatment of neurodegenerative diseases has been limited mainly because of the inability of the synthesized delivery systems to cross the blood-brain barrier and to successfully deliver their therapeutic cargo to the diseased tissue. Taking into consideration the aforementioned limitations, we designed a lipid-based nanotherapeutic vector composed of biomimetic lipids and CeO nanoparticles (nanoceria, NC). NC have shown to be a promising tool for the treatment of several pathological conditions ranging from cancer to neurological diseases, mainly because of their antioxidant properties, while lipid-based structures have been shown to have an inherent ability to cross the blood-brain barrier. The lipid-based nanotherapeutics were successfully fabricated using a combination of ultrasonication and high-pressure homogenization techniques, and they were fully characterized morphologically and physicochemically. Their antioxidant ability was demonstrated using electron paramagnetic resonance spectroscopy and antioxidant assays. These innovative nanotherapeutics demonstrated a higher colloidal stability with respect to free NC, preserving at the same time their antioxidant properties. Finally, the ability of the lipid carriers to cross a model of the blood-brain barrier and to be internalized by neurons, acting both as neuroprotective and pro-neurogenic agents, was demonstrated using single- and triple-culture systems.
神经退行性疾病包括一大类以突触连接显著丧失为特征的疾病，这种丧失是由神经退行性变导致的，而神经退行性变与活性氧和氮物种的过度产生密切相关。目前，神经退行性疾病的治疗受到限制，主要原因是合成的递送系统无法穿过血脑屏障并成功将其治疗物质递送至患病组织。考虑到上述局限性，我们设计了一种基于脂质的纳米治疗载体，其由仿生脂质和二氧化铈纳米颗粒（纳米铈，NC）组成。纳米铈已被证明是治疗从癌症到神经疾病等多种病理状况的有前景的工具，主要因其抗氧化特性，而基于脂质的结构已被证明具有穿越血脑屏障的内在能力。基于脂质的纳米治疗剂通过超声处理和高压均质技术的组合成功制备，并对其形态和物理化学性质进行了全面表征。使用电子顺磁共振光谱和抗氧化测定法证明了它们的抗氧化能力。这些创新的纳米治疗剂相对于游离纳米铈表现出更高的胶体稳定性，同时保留了它们的抗氧化特性。最后，使用单培养和三培养系统证明了脂质载体穿越血脑屏障模型并被神经元内化的能力，其兼具神经保护和促神经生成作用。
