Cyanine Phototruncation Enables Cell Labeling with Spatiotemporal Control

Abstract

Photoconvertible tracking strategies examine the dynamic migration of various cell populations. Here we develop phototruncation-assisted cell tracking (PACT) and apply it to evaluate the migration of immune cells into tumor-draining lymphatics. This approach is enabled by a recently discovered cyanine photoconversion reaction that leads to the two-carbon truncation and consequent blue-shift of these commonly used probes. By examining substituent effects on the heptamethine cyanine chromophore, we find that introduction of a single methoxy group increases the yield of the phototruncation reaction in neutral buffer by almost 8-fold. The resulting cell-tracking probes are applied in a series of in vitro and in vivo experiments, including quantitative, time-dependent measurements of the migra-tion of immune cells from tumors to tumor-draining lymph nodes. Unlike previously reported cellular photoconversion approaches, this method does not require genetic engineer-ing. Overall, PACT provides a straightforward approach to labeling cell populations with precise spatiotemporal con-trol.

Cyanine Renaissance: Tailoring the Properties to Applications

“…With the aim to overcome this limitation, Schnermann and coworkers set out to assess the effects of structure and substitution of the central chain on the chemical yield of phototruncation in their second work. [56] Screening a series of C3', C4', and C5'-substituted cyanines, they identified C3'-OMe-substituted cyanine as a prom-ising derivative that led to 8-fold enhancement under physiological conditions. Taking advantage of this, the authors developed phototruncation-assisted cell tracking (PACT) and applied it to evaluate the migration of immune cells into tumor-draining lymphatics (TDLNs).…”