Nanoscale
photodynamic therapy (PDT) is an appealing antitumor
modality for which apoptosis is the major mechanism of toxicity induction.
It was postulated that the highly reactive singlet oxygen in PDT could
deplete glutathione (GSH) and activate ferroptosis, the extent to
which could be further manipulated by a redox-responsive nanocarrier.
To validate this, a disulfide-bearing imidazole ligand coordinated
with zinc to form an all-active metal organic framework (MOF) nanocarrier
where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless
of light irradiation, the Ce6-loaded nanocarrier caused the depletion
of intracellular GSH via the disulfide–thiol exchange reaction
in a murine mammary carcinoma cell line (4T1). The GSH depletion further
caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement
of cytotoxicity that was alleviated by ferroptosis inhibitors. The
superior in vivo antitumor efficacy of the all-active
nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding
tumor growth suppression and animal survival rate. The coadministration
of an iron chelator weakened the antitumor potency of the nanocarrier
due to ferroptosis inhibition, which was supported by the fact of
tumor growth upsurge and the recovered GPX4 activity. The current
work highlights the contribution of ferroptotic machinery to antitumor
PDT via an activatable, adaptable, all-active MOF nanocarrier.
A novel, sensitive chemiluminescent (CL) immunoassay has been developed by taking advantage of a magnetic separation/mixing process and the amplification feature of colloidal gold label. First, the sandwich-type complex is formed in this protocol by the primary antibody immobilized on the surface of magnetic beads, the antigen in the sample, and the second antibody labeled with colloidal gold. Second, a large number of Au3+ ions from each gold particle anchored on the surface of magnetic beads are released after oxidative gold metal dissolution and then quantitatively determined by a simple and sensitive Au3+-catalyzed luminol CL reaction. Third, this protocol is evaluated for a noncompetitive immunoassay of a human immunoglobulin G, and a concentration as low as 3.1 x 10(-12) M is determined, which is competitive with colloidal gold-based anodic stripping voltammetry (ASV), colorimetric ELISA, or immunoassays based on fluorescent europium chelate labels. The high performance of this protocol is related to the sensitive CL determination of Au3+ ion (detection limit of 2 x 10(-10) M), which is 25 times higher than that by ASV at a single-use carbon-based screen-printed electrode. From the analytical chemistry point of view, this protocol will be quite promising for numerous applications in immunoassay and DNA hybridization.
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