Stimuli-Responsive Reversible Switching of Intersystem Crossing in Pure Organic Material for Smart Photodynamic Therapy.

Photosensitizers (PSs) with stimuli-responsive reversible switching of intersystem crossing (ISC) are highly promising for smart photodynamic therapy (PDT), but achieving this goal remains a tremendous challenge. This study introduces a strategy to obtain such reversible switching of ISC in a new class of PSs, which exhibit stimuli-initiated twisting of conjugated backbone. We present a multidisciplinary approach that includes femtosecond transient absorption spectroscopy and quantum chemical calculations. The organic structures reported show remarkably enhanced ISC efficiency (ΦISC ), switching from nearly 0 to 90 %, through an increase in the degree of twisting, providing an innovative mechanism to promote ISC. This leads us to propose here and demonstrate the concept of smart PDT, where pH-induced reversible twisting maximizes the ISC rate, and thus enables strong photodynamic action only under pathological stimulus (such as change in pH, hypoxia, or exposure to enzymes). The ISC process is turned off to deactivate PDT ability, when the PS is transferred or metabolized away from pathological region.

Manipulating Nonradiative Decay Channel by Intermolecular Charge Transfer for Exceptionally Improved Photothermal Conversion.

In-depth studies of nonradiative (NR) decay, seeking to maximize NR decay rate or manipulate other NR decay channels, are of greatest significance for improving the photothermal conversion efficiency (η) of organic materials for phototheranostics; however, to date, relevant work remains scarce. Here, we present an insightful study of NR decay in BODIPY (BDP) dye, in an aggregated state, i.e., in BDP nanoparticles (BDP NPs), which show an efficient additional NR decay channel from the aggregation-stabilized intermolecular charge transfer (CT) state, resulting in exceptionally high η (61%) for highly efficient phototheranostics in vivo. BDP NPs exhibit two ultrafast NR decay channels with ultrashort lifetimes of 1.7 and 50 ps, which is in stark contrast to the only S1 → S0 NR channel with a long lifetime of 373 ps in the isolated BDP dye. More importantly, the ultrafast NR channel (1.7 ps) in BDP NPs depletes a substantial portion of the excited-state population (71%), which accounts for its much better photothermal effect as compared with the isolated BDP dye. Finally, BDP NPs display a highly efficient photoacoustic imaging (PAI) guided photothermal therapy (PTT) of tumors in live mice. This study presents a deeper fundamental understanding of NR decay in organic materials, setting a valuable guideline that may be widely applicable to similar molecular structure to develop more advanced organic materials not only for photothermal-related applications.

Two-Photon-Induced Charge-Variable Conjugated Polyelectrolyte Brushes for Effective Gene Silencing.

Cationic conjugated polyelectrolytes can absorb negatively charged small interfering RNA (siRNA) and also visualize the cellular internalization of siRNA, which thus have been extensively explored as siRNA carriers. However, their low charge density cannot afford a high carrying capability, severely impeding gene transfection efficiency. Moreover, the intracellular controlled release of siRNA is another factor that limits the widespread use of siRNA therapeutics. Herein, we present a novel two-photon-induced charge-variable conjugated polyelectrolyte brush as an efficient siRNA carrier. This cationic conjugated polyelectrolyte brush (PPENBr-ONB) with densely cationic charges produces remarkable carrying capability with siRNA. In addition, PPENBr-ONB with large two-photon absorption (TPA) cross-section represents effective fluorescence resonance energy transfer (FRET) to photoresponsive side chain with 720 nm illumination for two-photon-induced photolysis. Hence, the charge transformation of the photoresponsive side chain from cations to zwitterions would remarkably elevate siRNA release. The obtained PPENBr-ONB shows considerable fluorescence quantum yields (0.16) in aqueous solution, sufficient to serve as a reporter for cellular imaging. Agarose gel electrophoresis experiments indicate that PPENBr-ONB exhibit excellent siRNA-loading capacity (1 mol PPENBr-ONB to more than 20 mol siRNA). Furthermore, PPENBr-ONB with large TPA cross-section (1.47 × 105 GM) exhibits promoted siRNA release (78%) under 720 nm illumination. In vitro experiment shows that PPENBr-ONB/siRNA complex could efficaciously knock out of targeted Plk1 mRNA to 24.7% under 720 nm illumination for 1 h. This two-photon excitation siRNA carrier offers an efficacious strategy for the exploitation of photo controlled gene delivery system.

Deciphering the intersystem crossing in near-infrared BODIPY photosensitizers for highly efficient photodynamic therapy.

Deciphering singlet-to-triplet intersystem crossing (ISC) in organic near-infrared photosensitizers (PSs) is of fundamental importance in the designing of high-performance PSs to boost the clinical usage of photodynamic therapy (PDT). However, in-depth investigations of the ISC dynamics in near-infrared PSs have not been performed to date. Here, systematical investigations of the ISC dynamics in organic near-infrared BODIPY derivatives are presented, in which a multi-channel yet remarkably efficient ISC process is revealed by ultrafast femtosecond transient absorption (fs-TA) spectroscopy and theoretical calculation. The fs-TA verifies an exceptionally enhanced ISC efficiency (Φ ISC = 91%) in iodine-substituted BODIPY (2I-BDP) which is further supported by the calculation results. This endows 2I-BDP with an ultrahigh singlet oxygen quantum yield (Φ Δ = 88%), thus enabling a proof-of-concept application of highly efficient PDT in vivo under ultralow near-infrared light power density (10 mW cm-2). The in-depth understanding of ISC dynamics in organic near-infrared materials may provide valuable guidance in the designing of novel organic theranostic materials for clinical cancer treatment.