The recent development of non-invasive imaging techniques has enabled the visualization of molecular events underlying cellular processes in live cells. Although microscopic objects can be readily manipulated at the cellular level, additional physiological insight is likely to be gained by manipulation of cells in vivo, which has not been achieved so far. Here we use infrared optical tweezers to trap and manipulate red blood cells within subdermal capillaries in living mice. We realize a non-contact micro-operation that results in the clearing of a blocked microvessel. Furthermore, we estimate the optical trap stiffness in the capillary. Our work expands the application of optical tweezers to the study of live cell dynamics in animals.
Photobiomodulation, by utilizing low-power light in the visible and near-infrared spectra to trigger biological responses in cells and tissues, has been considered as a possible therapeutic strategy for Alzheimer’s disease (AD), while its specific mechanisms have remained elusive. Here, we demonstrate that cognitive and memory impairment in an AD mouse model can be ameliorated by 1070-nm light via reducing cerebral β-amyloid (Aβ) burden, the hallmark of AD. The glial cells, including microglia and astrocytes, play important roles in Aβ clearance. Our results show that 1070-nm light pulsed at 10 Hz triggers microglia rather than astrocyte responses in AD mice. The 1070-nm light-induced microglia responses with alteration in morphology and increased colocalization with Aβ are sufficient to reduce Aβ load in AD mice. Moreover, 1070-nm light pulsed at 10 Hz can reduce perivascular microglia and promote angiogenesis to further enhance Aβ clearance. Our study confirms the important roles of microglia and cerebral vessels in the use of 1070-nm light for the treatment of AD mice and provides a framework for developing a novel therapeutic approach for AD.
Due to the high mobility of copper ions in numerous structurally-related phases, copper sulphide (Cu2−xS, 0 ≤ x ≤ 1) has been widely used as a starting template to fabricate various heterostructures via cation exchange. Such nanoheterostructures can possess unique combinations of physical properties that could be useful in diverse applications. Controllable methods of fabricating copper sulphide nanoheterostructures of increasing complexity have been rapidly emerging over the past few years. In this tutorial review, we discuss recent progress in heterostructure fabrication methods using copper sulphide. We primarily focus on important reports of cation exchange-based approaches and then summarize some key emerging applications that can employ these copper-sulphide-based nanoheterostructures.
Accurately locating and eradicating sporadically distributed cancer cells whilst minimizing damage to adjacent normal tissues is vital in image-guided tumor ablation. In this work, we developed four heptamethine cyanine based theranostic probes, IR1–4, that demonstrated unique pH switchable near-infrared (NIR) fluorescence and photothermal efficiency. While their fluorescence quantum yields increased up to 1020-fold upon acidification from pH 7.4 to 2.4, their photothermal efficiencies decreased up to 7.1-fold concomitantly. Theoretical calculations showed that protonation of the probes in an acidic environment increased the orbital energy gaps and reduced the intramolecular charge transfer efficiency, resulting in the conversion of absorbed light energy to NIR fluorescence instead of hyperthermia. Substitutions at the terminal indole of the probes fine-tuned their pKafluo values to a narrow physiological pH range of 4.0–5.3. IR2, with a pKafluo of 4.6, not only specifically illuminated cancer cells by sensing their more acidic lysosomal lumen, but also selectively ablated cancer cells via its maximized photothermal effects in the alkaline mitochondrial matrix. As far as we are aware, these probes not only offer the highest physiological acidity triggered NIR fluorescence enhancement as small molecules, but are also the first to specifically visualize and eradicate cancer cells by sensing their altered pH values in cellular organelles. Considering that a disordered pH in organelle lumen is a common characteristic of cancer cells, these theranostic probes hold the promise to be applied in image-guided tumor ablation over a wide range of tumor subtypes.