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, 1 2+) as a unique hydrogen sulfide (H2S)-responsive chromophore amenable to build H2S-activatable fluorescent probes (1 2+-semiconducting polymer nanoparticles, 1 2+-SNPs) for in vivo H2S detection. We demonstrate that EM 1 2+, with a strong absorption (500–850 nm), efficiently quenches the fluorescence (580, 700, or 830 nm) of different fluorophores within 1 2+-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 1 2+ 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.
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 H 2 S-activatable NIR afterglow probe (F1 2+-ANP). F1 2+-ANP displays a fast reaction rate (1563 ± 141 M −1 s −1) and large afterglow turn-on ratio (~122-fold) toward H 2 S, enabling high-sensitivity and-specificity measurement of H 2 S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H 2 Sactivatable afterglow probe (F1 2+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (<3 mm in diameter) and orthotopic liver tumors in mice. Strikingly, F1 2+-ANP-Gal accurately delineates tumor margins in excised hepatic cancer specimens, which may facilitate intraoperative guidance of hepatic cancer surgery.
Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r 1 relaxivity (∼60.0 mM–1 s–1 per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can accumulate preferentially in gastric tumors (∼23.4% ID%/g at 12 h) after intravenous injection into mice, creating opportunities for fluorescence/MR bimodal imaging-guided PTT of subcutaneous and metastatic gastric tumors. For the first time, accurate detection and laser irradiation-initiated photothermal ablation of orthotopic gastric tumors in intraoperative mice was also achieved. This study highlights the versatility of using a combination of dual biomarker recognition (i.e., αvβ3 and MMP-2) and dual modality imaging (i.e., MRI and NIR fluorescence) to design tumor-targeting and activatable nanoprobes with improved selectivity for cancer theranostics in vivo.
The noninvasive and specific detection of cancer cells in living subjects has been essential for the success of cancer diagnoses and treatments. Herein, we report a strategy of combining an αβ-integrin-receptor-targetable ligand, c-RGD, with the γ-glutamyl transpeptidase (GGT)-recognizable substrate, γ-glutamate (γ-Glu), to develop a tumor-targeting and GGT-activatable near-infrared (NIR)-fluorescent probe for the noninvasive imaging of tumors in living mice. We demonstrated that the probe's fluorescence was off initially, but when the γ-Glu in the probe was specifically cleaved by GGT, the fluorescent product was released and could be selectively taken up by U87MG-tumor cells via αβ-receptor-mediated endocytosis. Remarkably, enhanced intracellular NIR fluorescence distributed mainly in the lysosomes was observed in the tumor cells only, showing that the probe was capable of differentiating the tumor cells from the GGT-positive, αβ-deficient normal cells. Moreover, the probe also showed a high selectivity for the real-time and noninvasive detection of GGT activity in xenograft U87MG tumors following iv administration. This study reveals the advantage of using a combination of receptor-mediated cell uptake and molecular-target-triggered activation to design molecular probes for improved cancer imaging, which could facilitate effective cancer diagnoses.
Targeted delivery of intracellular stimuli-activatable photosensitizers (PSs) into tumor cells to achieve selective imaging and on-demand photodynamic therapy (PDT) of tumors has provided a vital opportunity for precise cancer diagnosis and therapy. In this paper, we report a tumor targeting and adenosine triphosphate (ATP)-activatable nanophotosensitizer Apt-HyNP/BHQ by modifying hybrid micellar nanoparticles with both nucleolin-targeting aptamer AS1411 and quencher BHQ-labeled ATP-binding aptamer BHQ-ATP-apt. We demonstrated that both of the fluorescence emissions at 555 and 627 nm were quenched by BHQ in Apt-HyNP/BHQ, resulting in low PDT capacity. After selective entry into tumor cells through nucleolin-mediated endocytosis, the high concentration of intracellular ATP could bind to BHQ-ATP-apt and trigger Apt-HyNP/BHQ dissociation, leading to turning "on" both fluorescence and PDT. The "off-on" fluorescence emissions at both 555 and 627 nm were successfully applied for dual color fluorescence imaging of endogenous ATP levels and real-time monitoring of intracellular activation of Apt-HyNP/BHQ in tumor cells. Moreover, imaging-guided precise PDT of tumors in living mice was also demonstrated, allowing for selective ablation of tumors without obvious side effects. This study highlights the potential of using a combination of tumor-targeting and ATP-binding aptamers to design ATP-activatable PSs for both fluorescence imaging and imaging-guided PDT of tumors in vivo.
Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allowenhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy(PDT) of tumors.However,the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo.Herein, we report tumor targeting,r edox-responsive magnetic and fluorogenic PS nanoassemblies (NP-RGD)s ynthesized via self-assembly of acRGD-and disulfide-containing fluorogenic and paramagnetic small molecule (1-RGD)f or fluorescence/ magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r 1 relaxivity but quenched fluorescence and PDT activity;d isulfide reduction by glutathione (GSH) promotes efficient disassembly into as mall-molecule probe (2-RGD)a nd an organic PS (PPa-SH), whichc ould further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors.
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