posted on 2021-09-07, 20:03authored byQiang Zhang, Tomoko Inose, Monica Ricci, Jiangtao Li, Ya Tian, Han Wen, Shuichi Toyouchi, Eduard Fron, Anh Thi Ngoc Dao, Hitoshi Kasai, Susana Rocha, Kenji Hirai, Beatrice Fortuni, Hiroshi Uji-i
Intracellular pH variations are a
crucial indicator of physiological
and pathological conditions. As such, cancer is known to have a direct
interplay with pH dysregulation. For investigation of the pH alterations
in cells, metal nanoparticles have been widely used as surface-enhanced
Raman scattering (SERS)-based sensors thanks to their high pH sensitivity.
However, these SERS probes allow for detection of the pH exclusively
at the acidic compartments of the cells (endolysosomes), where particles
are entrapped after their endocytosis. Consequently, the results obtained
with metal nanoparticles are limited, and the relationship between
the pH values detected in the cells and their physiological conditions
remains unclear. Herein, we propose an alternative approach based
on gold-deposited silver nanowire endoscopy to study cytosolic and
nuclear pH variations with high spatiotemporal resolution and sensitivity.
The sensing probe was fabricated by depositing gold nanostructures
on silver nanowires (Au-dep AgNWs) via visible-laser-light irradiation
and modifying the surface with a pH-responsive Raman reporter (4-mercaptobenzoic
acid). The high pH sensitivity was demonstrated by immersing the probe
in solutions with different pH values (4.4–9.3). The endoscopic
probe was then inserted into either the nucleus or cytosol of a living
HeLa cell for site-specific pH sensing. The same experiments were
performed after the addition of a hypoxia mimetic agent (CoCl2) and an anticancer drug (cisplatin), individually. Notably,
our probe accurately detected specific pH variations upon these treatments
over time. Similar pH alterations were not measured in untreated cells.
The results reported in this work clearly show that Au-dep AgNW endoscopy
is a promising powerful tool for pH-sensing applications in biological
systems.