Optical Property Control by the Interligand Charge Transfer Excited State in Brominated Homoleptic and Heteroleptic Aluminum Dinuclear Triple-Stranded Helicates.

The utilization of aluminum, an abundant and inexpensive element, for the synthesis of novel functional complexes is extremely important, but the design and control of photofunctionality are still unexplored. In this study, we focused on our previously developed dinuclear triple-stranded helicates incorporating two aluminum ions (ALPHY) to synthesize both homoleptic and heteroleptic complexes with bromine atoms at the 3-position of the pyrrole moiety in the Schiff base ligands. The brominated Schiff base ligands were reacted with AlCl3 to synthesize homoleptic complexes, while different ligands were mixed to prepare heteroleptic complexes. Single-crystal X-ray structural analysis revealed the structures of these novel complexes. We found that increasing the degree of bromination resulted in a tunable emission color, shifting progressively from 550 (yellow) to 566 nm (orange). Optical resolution of the complexes facilitated the observation of mirror-image circular dichroism and circularly polarized luminescence. Furthermore, employing ultrafast spectroscopy techniques, we have elucidated that the optical properties are governed by the interligand charge transfer (ILCT) among the three ligands. The formation of heteroleptic complexes induces the ILCT state even in nonpolar environments, thereby accelerating nonradiative decay and intersystem crossing. These findings mark significant advancements in photofunctional materials based on multinuclear complexes.

Smart Lipid Nanoparticle that Remodels Tumor Microenvironment for Activatable H2S Gas and Photodynamic Immunotherapy.

Hydrogen sulfide (H2S) has shown promise for gas therapy. However, it is still controversial whether H2S can remodel the tumor microenvironment (TME) and induce robust antitumor immunity. Here, a tumor-targeting and TME-responsive "smart" lipid nanoparticle (1-JK-PS-FA) is presented, which is capable of delivering and releasing H2S specifically in tumor tissues for on-demand H2S gas and photodynamic immunotherapy. 1-JK-PS-FA enables a burst release of H2S in the acidic TME, which promptly reduces the embedded organic electrochromic materials and consequently switches on near-infrared fluorescence and photodynamic activity. Furthermore, we found that high levels of H2S can reprogram the TME by reducing tumor interstitial fluid pressure, promoting angiogenesis, increasing vascular permeability, ameliorating hypoxia, and reducing immunosuppressive conditions. This leads to increased tumor uptake of 1-JK-PS-FA, thereby enhancing PDT efficacy and eliciting strong immunogenic cell death during 808 nm laser irradiation. Therefore, 1-JK-PS-FA permits synergistic H2S gas and photodynamic immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence. This work showcases the capacity of H2S to reprogram the TME to enhance H2S gas and immunotherapy.

A Ratiometric Photoacoustic Probe with a Reversible Response to Hydrogen Sulfide and Hydroxyl Radicals for Dynamic Imaging of Liver Inflammation.

Reversible imaging probes that allow for the dynamic visualization of the redox cycle between hydroxyl radical (⋅OH) and hydrogen sulfide (H2 S) are vital to probe the redox imbalance-involved pathological process in vivo. Herein, we report a reversible ratiometric photoacoustic (PA) imaging nanoprobe (1-PAIN) for the real-time imaging of ⋅OH/H2 S redox cycle in vivo. 1-PAIN displays a low PA ratio between 690 and 825 nm (PA690 /PA825 ), which significantly increases by ≈5-fold upon oxidation by ⋅OH, and is switched back to the initially low PA690 /PA825 value upon reduction by H2 S. 1-PAIN could dynamically report on the hepatic ⋅OH production in mice during the lipopolysaccharide (LPS)-induced liver inflammation process, and visualize hepatic H2 S generation during the N-acetyl cysteine (NAC)-induced anti-inflammation process. 1-PAIN can act as a useful tool to probe the redox state in living biology, beneficial for the study of redox imbalance-related diseases.

An Activatable Afterglow/MRI Bimodal Nanoprobe with Fast Response to H2 S for In Vivo Imaging of Acute Hepatitis.

Accurate detection of hepatic hydrogen sulfide (H2 S) to monitor H2 S-related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2 S. Here, we report a H2 S-activatable near-infrared afterglow/MRI bimodal probe F1-GdNP, which shows an "always-on" MRI signal and "off-on" afterglow signal toward H2 S. F1-GdNP shows fast response, high sensitivity and specificity toward H2 S, permitting afterglow imaging of H2 S and evaluation of cystathionine γ-lyase (CSE)'s activity in living mice. We further employ the high spatial-resolution MRI signal of F1-GdNP to track its delivery and accumulation in liver. Importantly, F1-GdNP offers a high signal-to-background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2 S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1-GdNP for monitoring of acute hepatitis process in vivo.

Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy.

Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.

Hysteretic Three-State Redox Interconversion among Zigzag Bisquinodimethanes with Non-fused Benzene Rings and Twisted Tetra-/Dications with [5]/[3]Acenes Exhibiting Near-Infrared Absorptions.

Octaaryl-substituted bisquinodimethanes (BQDs) with a zigzag structure were designed as redox-switchable molecules that undergo four-electron oxidation to produce tetracationic pentacenes with a doubly twisted structure. In contrast to one-stage four-electron oxidation of BQDs, stepwise two-electron reduction of tetracationic pentacenes occurs to give dicationic anthracenes and then the original BQDs, step-by-step. Since both tetracations and dications exhibit near-infrared (NIR) absorptions (-1400 nm) based on an intramolecular charge-transfer interaction, changes in not only their structures but also their UV-vis-NIR spectra can be controlled by redox stimuli. In this Communication, we present an unprecedented one-step π-extension to pentacene from non-fused benzene rings by oxidation, and subsequent two-stage deannulation to benzene rings via anthracene upon reduction. All structures were determined by single-crystal X-ray analyses, and their properties were characterized by spectroscopic and theoretical studies.

H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo.

Afterglow luminescent probes with high signal-to-background ratio show promise for in vivo imaging; however, such probes that can be selectively delivered into target sites and switch on afterglow luminescence remain limited. We optimize an organic electrochromic material and integrate it into near-infrared (NIR) photosensitizer (silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) and (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) containing nanoparticles, developing an H2S-activatable NIR afterglow probe (F12+-ANP). F12+-ANP displays a fast reaction rate (1563 ± 141 M-1 s-1) and large afterglow turn-on ratio (~122-fold) toward H2S, enabling high-sensitivity and -specificity measurement of H2S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H2S-activatable afterglow probe (F12+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (<3 mm in diameter) and orthotopic liver tumors in mice. Strikingly, F12+-ANP-Gal accurately delineates tumor margins in excised hepatic cancer specimens, which may facilitate intraoperative guidance of hepatic cancer surgery.

Engineering of Electrochromic Materials as Activatable Probes for Molecular Imaging and Photodynamic Therapy.

Electrochromic materials (EMs) are widely used color-switchable materials, but their applications as stimuli-responsive biomaterials to monitor and control biological processes remain unexplored. This study reports the engineering of an organic π-electron structure-based EM (dicationic 1,1,4,4-tetraarylbutadiene, 12+) as a unique hydrogen sulfide (H2S)-responsive chromophore amenable to build H2S-activatable fluorescent probes (12+-semiconducting polymer nanoparticles, 12+-SNPs) for in vivo H2S detection. We demonstrate that EM 12+, with a strong absorption (500-850 nm), efficiently quenches the fluorescence (580, 700, or 830 nm) of different fluorophores within 12+-SNPs, while the selective conversion into colorless diene 2 via H2S-mediated two-electron reduction significantly recovers fluorescence, allowing for non-invasive imaging of hepatic and tumor H2S in mice in real time. Strikingly, EM 12+ is further applied to design a near-infrared photosensitizer with tumor-targeting and H2S-activatable ability for effective photodynamic therapy (PDT) of H2S-related tumors in mice. This study demonstrates promise for applying EMs to build activatable probes for molecular imaging of H2S and selective PDT of tumors, which may lead to the development of new EMs capable of detecting and regulating essential biological processes in vivo.