New “Destruction Seek to Survive” Strategy Based on a Serum Albumin Assembly with a Squaraine Molecule for the Detection of Peroxynitrite

Peroxynitrite (ONOO-), a kind of active nitrogen species, plays an important role in biological systems. Overproduction of ONOO- is closely related to the pathogenesis of many diseases. Therefore, it is necessary to quantify intracellular ONOO- for differentiating health and disease states. Fluorescent probes with near-infrared (NIR) fluorescence can detect ONOO- with high sensitivity and selectivity. However, there is an inevitable problem that many NIR fluorophores are easily oxidized by ONOO- to give a false-negative result. To avoid this problem, herein, we ingeniously propose a "destruction to seek to survive" strategy to detect ONOO-. Two NIR squaraine (SQ) dyes were connected together to form a fluorescent probe (SQDC). This method utilizes the destructive effect of peroxynitrite on one of the SQ moieties of SQDC to eliminate the steric hindrance, enabling the other "survived" SQ segment to enter the hydrophobic cavity of bovine serum albumin (BSA) via the well-known host-guest interactions. The encapsulation of albumin protects the "survived" SQ from further attack of ONOO-. As a result, a NIR fluorescence turn-on response coming from the host-guest interaction between BSA and the "survived" SQ escaped from SQDC was found, which can be used for the detection of ONOO-. The assembly of SQDC mixed with BSA can be located in mitochondria to detect endogenous and exogenous ONOO- sensitively in living cells. As a proof-of-concept method, it is envisioned that this novel detection strategy with a simple assembly would become a powerful means for the detection of ONOO- when employing NIR fluorophores.