Aggregation Enhanced Responsiveness of Rationally Designed Probes to Hydrogen Sulfide for Targeted Cancer Imaging

Abstract

Activatable molecular probes hold great promise for targeted cancer imaging. However, the hydrophobic nature of most conventional probes makes them generate precipitated agglomerate in aqueous media, thereby annihilating their responsiveness to analytes and precluding their practical applications for bioimaging. This study reports the development of two small molecular probes with unprecedented aggregation enhanced responsiveness to H 2 S for in vivo imaging of H 2 S-rich cancers. The subtle modulation of the equilibrium between hydrophilicity and lipophilicity by N-methylpyridinium endows these designed probes with the capability of spontaneously self-assembling into nanoprobes under physiological conditions. Such probes in an aggregated state, rather than a molecular dissolved state, show NIR fluorescence light up and photoacoustic signals turn on upon H 2 S specific activation, allowing in vivo visualization and differentiation of cancers based on differences in H 2 S content. Thus, our study presents an effective design strategy which should pave the way to molecular design of optimized probes for precision cancer diagnostics.

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

“…BODIPYs are well-known fluorophores that have found wide applications in diverse research fields. [57][58][59] They show superior characteristics such as high extinction coefficients, excellent photostability and rich synthetic functionalization [60][61] , making them ideal for building PSs. [62][63] Compounds 1-5 are regular BODIPYs attached with different substitutions on the BODIPY cores.…”

Stable twisted conformation aza-BODIPY NIR-II fluorescent nanoparticles with ultra-large Stokes shift for imaging-guided phototherapy

“…As a famous family of fluorescent dyes, BODIPYs have attracted a lot of attention in biological molecule detection, 12,13 tumor imaging, 14 and photothermal and photodynamic therapies 15–19 due to their outstanding characters including intense absorption at relatively long wavelength, facile synthesis, and modification, and brilliant optical and chemical stability. 20 But the majority of BODIPY molecules only exhibit fluorescence emission in the NIR-I region.…”

A naphthalimide-based peptide conjugate for concurrent imaging and apoptosis induction in cancer cells by utilizing endogenous hydrogen sulfide

“…4,8 An emerging strategy for treating cancer is targeting their "unique" property of producing endogenous H 2 S that allows differentiating between healthy and malignant tissue. 9 Consequently, there is an active search for theranostic agents to exploit the H 2 S sensing ability and in this context, several detection methods [10][11][12][13][14][15] have been developed in recent years to sense endogenous H 2 S. [16][17][18][19][20] Some fluorescent probes based on naphthalimide 21,22 , rhodamine 23 , fluorescein 24,25 , and cyanine, 26,27 are good in sensitivity and selectivity among others but there are very few reported schemes that can sense endogenous H 2 S and impede cancer cell proliferation at the same time. 28,29 Scheme 1.…”