ZIF-8 Microswimmers Self-Fast Dynamic Destruction in Microliter Volumes of Cerebrospinal Fluid Samples: Toward a Selective Assessment of Amyloidosis

Herein, we describe the synthesis of magnetic zeolitic imidazole framework (ZIF-8) microswimmers for detecting and quantifying the amyloid beta (Aβ_1-42) peptide in cerebrospinal fluid (CSF) samples, which are used as a biomarker of amyloidosis for diagnosing Alzheimer's disease (AD). The microswimmers are prepared by external decoration of the ZIF-8 with magnetic Fe₃O₄ nanoparticles, followed by post internal encapsulation of quinine as fluorescent probe. The magnetic and surface properties of the microswimmers are fine-tuned to obtain tailored structures with an inner porous structure with the loaded fluorescent probe and outer magnetic engines. A macroporous structure was preferred over a microporous structure for quinine encapsulation, increasing the loading efficiency by about 50%, allowing also external decoration of the ferrite to impart the desired magnetic properties to the microswimmer. The principle for detection relies on the specific affinity of target sequence of amino acids in the Aβ_1-42 peptide structure toward the Zn units in the ZIF-8, resulting in the self-destruction of the microswimmers and subsequent release of quinine in a concentration-dependent manner. The use of the bioreceptor-free magnetic assisted microswimmers allows for direct assessment of Aβ_1-42 peptide in only 10 μL of CSF samples in just 10 min. Excellent analytical performance with a limit of detection of 40 pg/mL and a linear range ranging from 140 to 1200 pg/mL (r = 0.9990), covering the range in the clinical practice, is obtained. An excellent selectivity was also obtained toward the Aβ_1-42 peptide which approaches an excellent assessment of amyloidosis in the human brain, as demonstrated by the good correlation obtained (r = 0.97) between the quantitative levels obtained in our microswimmers approach in comparison with the enzyme-linked immunosorbent assay method in diagnosed CSF samples from patients where Tau protein was also determined due to its coexistence with Aβ_1-42 peptides. Since CSF biomarkers are currently the only clinically validated biofluid diagnostic test for AD, our approach will drastically reduce the volume required to determine Aβ levels, reducing the impact of the side effects of lumbar puncture in clinical practice. It became a novel bioreceptor-free approach to more easily, less invasively measure Aβ_1-42 peptide in CSF, becoming a valuable tool for indirect amyloidosis prediction in brain tissues in the patient's lifetime, opening the possibility for early treatment of the AD.