Background: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer’s disease (AD), and the formation of amyloid-β (Aβ) plaques induces critical impairment of cognitive function. Objective: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. Methods: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aβ plaques by electron emission from magnetite. The reduction in Aβ plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aβ-magnetite and Aβ fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. Results: Single PS induced a 48–87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aβ plaque burden (68–82%) and (94–97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p <  0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aβ fibrils. Conclusion: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

Inexpensive near-infrared microscopy (NIRM) was developed as a convenient technique to detect the medulla loss of scalp hair while reducing analytical time with easy sample preparation, leading to a field screening tool for breast cancer. NIRM has been evaluated as an alternative to synchrotron-based nanoscopy and to the relatively expensive method of conventional infrared microscopy to determine the degree and pattern of medulla loss of scalp hairs of patients with breast cancer and benign diseases, as well as normal healthy individuals. NIR imaging showed a strong, scattering-based hyperintense contrast of the medulla compared to the fully attenuated cortex in medullated healthy hair. Complete medulla loss (CML) per hair strand was more extensively (60.9 AE 10.2%) (p < 0.001) detected in the hair of all cancer patients than in the hair of either healthy individuals (less than 3.7 AE 7.5%) or those with benign disease (30.6 AE 5.9%), suggesting a potential biomarker for breast cancer diagnosis. The medulla structure was retained mostly in the hair of age-matched healthy individuals, but discontinuous medulla loss was observed concomitantly with less CML in fibroadenoma patients. Potentially, compact NIRM modules can be integrated into a mobile platform as point-of-care technology for breast cancer screening.

In view of the fact that Bragg peak energy cannot be delivered individually to multiple scattered infiltrating tumors or diffuse lesions, the energy of the ion beam could instead be adjusted to traverse the entire body for the selective activation of nanoparticles (NPs) inside the target lesions with an ion fluence comparable to the Bragg peak. This Coulomb stimulation of NPs generates low-energy electrons (LEEs) and characteristic fluorescent X-rays (XFLs) from the NP surface; this effectively transforms inert NPs into nanoradiators, much like the conversion of a prodrug into a drug. In contrast, the relatively small plateau dose absorbed along the beam path ensures that there are minimal effects to normal tissue (NT). This simple but innovative approach enables unprecedented traversing ion beam stimulation therapy (TIBS) for infiltrating tumors or diffuse non-oncological lesions. The theoretical background and efficacy of TIBS has been demonstrated by several proof-of-concept studies with animal disease models and molecular-targeted high-Z NPs.

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