Click Synthesis Enabled Sulfur Atom Strategy for Polymerization‐Enhanced and Two‐Photon Photosensitization

Abstract

Facile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst‐free thiol–yne click reaction was employed to develop the sulfur atom‐based PSs by using the in situ formed sulfur “heavy atom effect” to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine‐based aggregation‐induced emission (AIE) unit was also advantageous in PS design by suppressing their non‐radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double‐bond π bridge and AIE electron acceptor, created a donor‐π‐acceptor (D‐π‐A) molecular system with good two‐photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two‐photon‐excited PDT towards cancer cells, therefore possessing a huge potential for the deep‐tissue disease therapy.

Ion−π interactions for constructing organic luminescent materials

“…By virtue of superior selectivity, high sensitivity, operation convenience, and noninvasiveness, organic luminescent materials are widely used in bioimaging of specific organelles, diagnosing diseases, and dynamic evaluation of the treatment outcomes. [110][111][112][113][114] However, as a result of π−π interactions, bioimaging performance of traditional organic luminescent materials with large π−conjugation suffered a lot from luminescence quenching after they accumulated into cells, tissues, or live animals. Ion−π type organic luminogens are beneficial for the subcellular localization driven by both electrostatic and ion−π interactions.…”

Ir(III) Complexes with AIE Characteristics for Biological Applications

“…In recent years, two-photon absorption (TPA) has emerged as an attractive protocol in bioimaging and PDT. Two-photon photodynamic therapy (TP-PDT) activates PSs by contemporaneously absorbing two photons [ 53 , 54 , 55 , 56 ]. It provides photodamage and phototoxicity as well as deeper penetration, weaker autofluorescence and lower photobleaching [ 57 , 58 ].…”

X-Yne Click Polymerization

“…Recently, Chen and Tang et al proposed a new strategy for the preparation of sulfur-containing polymeric photosensitizers (PSs) by this spontaneous thiol-yne click polymerization (Figure 1D). 30 The introduction of sulfur atom induced a "heavy atom effect" so as to enhance the intersystem crossing (ISC) process of PSs, thereby further promoting the generation of reactive oxygen species (ROS). More importantly, this effect could be significantly amplified by polymerization.…”