Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy.

Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.

A histone deacetylase, FaSRT1-2, plays multiple roles in regulating fruit ripening, plant growth and stresses resistance of cultivated strawberry.

Sirtuins (SRTs) are a group of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that target both histone and nonhistone proteins. The biological function of SRT in horticultural plants has been rarely studied. In this study, FaSRT1-2 was identified as a key member of the 8 FaSRTs encoded in cultivated strawberry genome. Transient overexpression of FaSRT1-2 in strawberry fruit accelerated ripening, increased the content of anthocyanins and sugars, enhanced ripening-related gene expression. Moreover, stable transformation of FaSRT1-2 in strawberry plants resulted in enhanced vegetative growth, increased sensitivity to heat stress and increased susceptibility to Botrytis cinerea infection. Interestingly, knocking out the homologous gene in woodland strawberry had the opposite effects. Additionally, we found the content of stress-related hormone abscisic acid (ABA) was decreased, while the growth-related gibberellin (GA) concentration was increased in FaSRT1-2 overexpression lines. Gene expression analysis revealed induction of heat shock proteins, transcription factors, stress-related and antioxidant genes in the FaSRT1-2-overexpressed plants while knocked-out of the gene had the opposite impact. In conclusion, our findings demonstrated that FaSRT1-2 could positively promote strawberry plant vegetative growth and fruit ripening by affecting ABA and GA pathways. However, it negatively regulates the resistance to heat stress and B. cinerea infection by influencing the related gene expression.

Evaluation and Comparison of Academic Impact and Disruptive Innovation Level of Medical Journals: Bibliometric Analysis and Disruptive Evaluation.

BACKGROUND: As an important platform for researchers to present their academic findings, medical journals have a close relationship between their evaluation orientation and the value orientation of their published research results. However, the differences between the academic impact and level of disruptive innovation of medical journals have not been examined by any study yet. OBJECTIVE: This study aims to compare the relationships and differences between the academic impact, disruptive innovation levels, and peer review results of medical journals and published research papers. We also analyzed the similarities and differences in the impact evaluations, disruptive innovations, and peer reviews for different types of medical research papers and the underlying reasons. METHODS: The general and internal medicine Science Citation Index Expanded (SCIE) journals in 2018 were chosen as the study object to explore the differences in the academic impact and level of disruptive innovation of medical journals based on the OpenCitations Index of PubMed open PMID-to-PMID citations (POCI) and H1Connect databases, respectively, and we compared them with the results of peer review. RESULTS: First, the correlation coefficients of the Journal Disruption Index (JDI) with the Journal Cumulative Citation for 5 years (JCC5), Journal Impact Factor (JIF), and Journal Citation Indicator (JCI) were 0.677, 0.585, and 0.621, respectively. The correlation coefficient of the absolute disruption index (Dz) with the Cumulative Citation for 5 years (CC5) was 0.635. However, the average difference in the disruptive innovation and academic influence rankings of journals reached 20 places (about 17.5%). The average difference in the disruptive innovation and influence rankings of research papers reached about 2700 places (about 17.7%). The differences reflect the essential difference between the two evaluation systems. Second, the top 7 journals selected based on JDI, JCC5, JIF, and JCI were the same, and all of them were H-journals. Although 8 (8/15, 53%), 96 (96/150, 64%), and 880 (880/1500, 58.67%) of the top 0.1%, top 1%, and top 10% papers selected based on Dz and CC5, respectively, were the same. Third, research papers with the "changes clinical practice" tag showed only moderate innovation (4.96) and impact (241.67) levels but had high levels of peer-reviewed recognition (6.00) and attention (2.83). CONCLUSIONS: The results of the study show that research evaluation based on innovative indicators is detached from the traditional impact evaluation system. The 3 evaluation systems (impact evaluation, disruptive innovation evaluation, and peer review) only have high consistency for authoritative journals and top papers. Neither a single impact indicator nor an innovative indicator can directly reflect the impact of medical research for clinical practice. How to establish an integrated, comprehensive, scientific, and reasonable journal evaluation system to improve the existing evaluation system of medical journals still needs further research.

Molecular Imaging of Renin Activity using Fluorogenic Nanoprobes for Precision Antihypertensive Therapy.

Life-threatening hypertension remains inadequately controlled in clinics due to its heterogenous renin levels. Rapid stratification of hypertension through renin analysis is crucial for effective personalized treatment, yet an ultrasensitive detection approach is currently lacking. Here, we report activatable renin nanoprobes (ARNs) for non-invasive and ultrasensitive profiling of renin activity and guiding antihypertensive treatment decision through near-infrared fluorescence (NIRF) in vivo imaging and in vitro urinalysis. ARNs are intrinsically non-fluorescent due to NIRF reporter connected to a gold nanocluster through a renin-responsive peptide. In hyperreninemia mouse models, ARNs specifically react with renin to liberate the renal clearable NIRF reporter for accurate renin detection that outperforms the gold standard radioimmunoassay. Such specific and sensitive detection also enables imaging-based high-throughput screening of antihypertensive drugs. In hypertensive rat models, ARNs enable ultrasensitive detection of both plasma and urinary renin, facilitating renin-guided precision treatment and significantly improving hypertension control rate (90% versus 58%). Our nanoprobe platform holds great potential for assisting clinicians in rapidly and accurately classifying hypertensive patients and improving outcomes through tailored treatment selection.

Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection.

Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test.

Molecular Probes for Autofluorescence-Free Optical Imaging.

Optical imaging is an indispensable tool in clinical diagnostics and fundamental biomedical research. Autofluorescence-free optical imaging, which eliminates real-time optical excitation to minimize background noise, enables clear visualization of biological architecture and physiopathological events deep within living subjects. Molecular probes especially developed for autofluorescence-free optical imaging have been proven to remarkably improve the imaging sensitivity, penetration depth, target specificity, and multiplexing capability. In this Review, we focus on the advancements of autofluorescence-free molecular probes through the lens of particular molecular or photophysical mechanisms that produce long-lasting luminescence after the cessation of light excitation. The versatile design strategies of these molecular probes are discussed along with a broad range of biological applications. Finally, challenges and perspectives are discussed to further advance the next-generation autofluorescence-free molecular probes for in vivo imaging and in vitro biosensors.

Genome-Wide Identification and Comparative Transcriptome Methods Reveal FaMDHAR50 Regulating Ascorbic Acid Regeneration and Quality Formation of Strawberry Fruits.

Ascorbic acid (AsA) is a crucial water-soluble antioxidant in strawberry fruit, but limited research is currently available on the identification and functional validation of key genes involved in AsA metabolism in strawberries. This study analyzed the FaMDHAR gene family identification, which includes 168 genes. Most of the products of these genes are predicted to exist in the chloroplast and cytoplasm. The promoter region is rich in cis-acting elements related to plant growth and development, stress and light response. Meanwhile, the key gene FaMDHAR50 that positively regulates AsA regeneration was identified through comparative transcriptome analysis of 'Benihoppe' strawberry (WT) and its natural mutant (MT) with high AsA content (83 mg/100 g FW). The transient overexpression experiment further showed that overexpression of FaMDHAR50 significantly enhanced the AsA content by 38% in strawberry fruit, with the upregulated expression of structural genes involved in AsA biosynthesis (FaGalUR and FaGalLDH) and recycling and degradation (FaAPX, FaAO and FaDHAR) compared with that of the control. Moreover, increased sugar (sucrose, glucose and fructose) contents and decreased firmness and citric acid contents were observed in the overexpressed fruit, which were accompanied by the upregulation of FaSNS, FaSPS, FaCEL1 and FaACL, as well as the downregulation of FaCS. Additionally, the content of pelargonidin 3-glucoside markedly decreased, while cyanidin chloride increased significantly. In summary, FaMDHAR50 is a key positive regulatory gene involved in AsA regeneration in strawberry fruit, which also plays an important role in the formation of fruit flavor, apperance and texture during strawberry fruit ripening.

Size-Transformable Superoxide-Triggered Nanoreporters for Crosstalk-Free Dual Fluorescence/Chemiluminescence Imaging and Urinalysis in Living Mice.

Chemiluminescence imaging has been recognized as a valuable tool for ultrasensitive detection of physio-pathological events through elimination of background autofluorescence. However, most chemiluminescent nanoprobes suffer from shallow imaging depths and slow clearance from living bodies, which impede their use in clinical settings. We herein report size-transformable nanoreporters (ADN1 and ADN2) that could be activated at disease site by superoxide anion (O2 ⋅- ) to trigger nanostructure disassembly into renal excretable fluorescent fragments as well as chemiluminescence turn-on for crosstalk-free duplex chemo-fluorescence imaging and in vitro urinalysis. In peritonitis mouse model, we demonstrate that the representative nanoreporter ADN1 spontaneously accumulates at the disrupted peritoneum and is cleaved by upregulated O2 ⋅- to initiate depolymerization and result in red chemiluminescence at 620 nm, enabling sensitive detection of peritonitis at least 19 h earlier than gold standard histological assays. Additionally, the incorporation of a near-infrared (NIR) dye into ADN1 results in ADN2 exhibiting intense and red-shifted chemiluminescence at ≈800 nm, which permits early detection of deeply seated diseases such as drug-induced hepatotoxicity. This study thus showcases a modular design strategy that is not only applicable to developing versatile chemiluminescent nanoprobes with switchable pharmacokinetics for early disease diagnosis, but also promising for future clinical translations.

Molecular Chemiluminescent Probes with a Very Long Near-Infrared Emission Wavelength for in†Vivo Imaging.

Chemiluminescence imaging is imperative for diagnostics and imaging due to its intrinsically high sensitivity. To improve in vivo detection of biomarkers, chemiluminophores that simultaneously possess near-infrared (NIR) emission and modular structures amenable to construction of activatable probes are highly desired; however, these are rare. Herein, we report two chemiluminophores with record long NIR emission (>750 nm) via integration of dicyanomethylene-4H-benzothiopyran or dicyanomethylene-4H-benzoselenopyran with dioxetane unit. Caging of the chemiluminophores with different cleavable moieties produces NIR chemiluminescence probes (NCPs) that only produce signals upon reaction with reactive oxygen species or enzymes, for example, ß-galactosidase, with a tissue-penetration depth of up to 2 cm. Thus, this study provides NIR chemiluminescence molecular scaffolds applicable for in vivo turn-on imaging of versatile biomarkers in deep tissues.

Semiconducting Polycomplex Nanoparticles for Photothermal Ferrotherapy of Cancer.

This study reports the development of iron-chelated semiconducting polycomplex nanoparticles (SPFeN) for photoacoustic (PA) imaging-guided photothermal ferrotherapy of cancer. The hybrid polymeric nanoagent comprises a ferroptosis initiator (Fe3+ ) and an amphiphilic semiconducting polycomplex (SPC ) serving as both the photothermal nanotransducer and iron ion chelator. By virtue of poly(ethylene glycol) (PEG) grafting and its small size, SPFeN accumulates in the tumor of living mice after systemic administration, which can be monitored by PA imaging. In the acidic tumor microenvironment, SPFeN generates hydroxyl radicals, leading to ferroptosis; meanwhile, under NIR laser irradiation, it generates localized heat to not only accelerate the Fenton reaction but also implement photothermal therapy. Such a combined photothermal ferrotherapeutic effect of SPFeN leads to minimized dosage of iron compared to previous studies and effectively inhibits the tumor growth in living mice, which is not possible for the controls.

A Renal-Clearable Macromolecular Reporter for Near-Infrared Fluorescence Imaging of Bladder Cancer.

Bladder cancer (BC) is a prevalent disease with high morbidity and mortality; however, in vivo optical imaging of BC remains challenging because of the lack of cancer-specific optical agents with high renal clearance. Herein, a macromolecular reporter (CyP1) was synthesized for real-time near-infrared fluorescence (NIRF) imaging and urinalysis of BC in living mice. Because of the high renal clearance (ca. 94 % of the injection dosage at 24 h post-injection) and its cancer biomarker (APN=aminopeptidase N) specificity, CyP1 can be efficiently transported to the bladder and specially turn on its NIRF signal to report the detection of BC in living mice. Moreover, CyP1 can be used for optical urinalysis, permitting the ex vivo tracking of tumor progression for therapeutic evaluation and easy translation of CyP2 as an in vitro diagnostic assay. This study not only provides new opportunities for non-invasive diagnosis of BC, but also reveals useful guidelines for the development of molecular reporters for the detection of bladder diseases.

Photoactivatable Organic Semiconducting Pro-nanoenzymes.

Therapeutic enzymes hold great promise for cancer therapy; however, in vivo remote control of enzymatic activity to improve their therapeutic specificity remains challenging. This study reports the development of an organic semiconducting pro-nanoenzyme (OSPE) with a photoactivatable feature for metastasis-inhibited cancer therapy. Upon near-infrared (NIR) light irradiation, this pro-nanoenzyme not only generates cytotoxic singlet oxygen (1O2) for photodynamic therapy (PDT), but also triggers a spontaneous cascade reaction to induce the degradation of ribonucleic acid (RNA) specifically in tumor microenvironment. More importantly, OSPE-mediated RNA degradation is found to downregulate the expression of metastasis-related proteins, contributing to the inhibition of metastasis after treatment. Such a photoactivated and cancer-specific synergistic therapeutic action of OSPE enables complete inhibition of tumor growth and lung metastasis in mouse xenograft model, which is not possible for the counterpart PDT nanoagent. Thus, our study proposes a phototherapeutic-proenzyme approach toward complete-remission cancer therapy.

Multimodal Biophotonics of Semiconducting Polymer Nanoparticles.

Biophotonics as an interdisciplinary frontier plays an increasingly important role in modern biomedical science. Optical agents are generally involved in biophotonics to interpret biomolecular events into readable optical signals for imaging and diagnosis or to convert photons into other forms of energy (such as heat, mechanical force, or chemical radicals) for therapeutic intervention and biological stimulation. Development of new optical agents including metallic nanoparticles, quantum dots, up-conversion nanoparticles, carbon dots, and silica nanoparticles has contributed to the advancement of this field. However, most of these agents have their own merits and demerits, making them less effective as multimodal biophotonic platforms. In this Account, we summarize our recent work on the development of near-infrared (NIR) semiconducting polymer nanoparticles (SPNs) as multimodal light converters for advanced biophotonics. SPNs are composed of π-electron delocalized semiconducting polymers (SPs) and often possess the advantages of good biocompatibility, high photostability, and large absorption coefficients. Because the photophysical properties of SPNs are mainly determined by the molecular structures of the precursor polymers, molecular engineering allows us to fine tune their photophysical processes to obtain different optical responses, even to light in the second NIR window (1000-1700 nm). Meanwhile, the facile nanoformulation methods of SPNs enable alteration of their outer and inner structures for diverse biological interactions. The unique photophysical properties of SPNs have brought about ultrasensitive deep-tissue molecular imaging. NIR-absorbing SPNs with strong charge-transfer backbones can convert photoenergy into mechanical acoustic waves, permitting photoacoustic imaging that bypasses the issue of light scattering and reaches the centimeter tissue penetration depth. Differently, phenylenevinylene-containing SPNs can store photon energy via chemical defects and emit long-NIR afterglow luminescence with a half-life of ∼6 min after cessation of light excitation. Such an afterglow process avoids tissue autofluorescence, giving rise to ultrahigh signal-to-background ratios. So far, SPN-based molecular photoacoustic or afterglow probes have been developed to image disease tissues (tumors), biomarkers (biothiols and reactive oxygen species), and physiological indexes (pH and temperature) in different preclinical animal models. The synthetic flexibility of SPNs further permits light-modulated biological and therapeutic interventions. Till now, SPNs with high photothermal conversion efficiencies have been shaped into photothermal transducers to remotely regulate biological events including protein ion channels, enzymatic activity, and gene expression. In conjunction with the desired biodistribution and tumor-homing ability, SPNs have been doped or coated with other inorganic agents for amplified photothermal or self-regulated photodynamic cancer therapy. This Account thus demonstrates that SPNs serve as a multimodal biophotonic nanoplatform to provide unprecedented opportunities for molecular imaging, noninvasive bioactivation, and advanced therapy.

Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer Therapy.

Nanomedicine have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser irradiation at the time scale of seconds, the nanoagonists can repeatedly and locally release Cap to multiply activate TRPV1 channels on the cellular membrane; the cumulative effect is the overinflux of ions in mitochondria followed by the induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple transient activation of TRPV1 channels is essential to induce such a cell death both in vitro and in vivo because both free Cap and simple Cap-encapsulated nanoparticles fail to do so. The photothermally triggered release also ensures a high local concentration of the TRPV1 agonist at tumor site, permitting specific cancer cell therapy at a low systemic administration dosage. Our study thus demonstrates the first example of ion-channel-specific and remote-controlled drug-delivery system for cancer cell therapy.

A Semiconducting Polymer Nano-prodrug for Hypoxia-Activated Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) holds great promise for cancer therapy; however, its efficacy is often compromised by tumor hypoxia. Herein, we report the synthesis of a semiconducting polymer nanoprodrug (SPNpd) that not only efficiently generates singlet oxygen (1 O2 ) under NIR photoirradiation but also specifically activates its chemotherapeutic action in hypoxic tumor microenvironment. SPNpd is self-assembled from a amphiphilic polymer brush, which comprises a light-responsive photodynamic backbone grafted with poly(ethylene glycol) and conjugated with a chemodrug through hypoxia-cleavable linkers. The well-defined and compact nanostructure of SPNpd (30 nm) enables accumulation in the tumor of living mice. Owing to these features, SPNpd exerts synergistic photodynamic and chemo-therapy, and effectively inhibits tumor growth in a xenograft tumor mouse model. This study represents the first hypoxia-activatable phototherapeutic polymeric prodrug system with a high potential for cancer therapy.

Renal-clearable Molecular Semiconductor for Second Near-Infrared Fluorescence Imaging of Kidney Dysfunction.

Real-time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical agents with high renal clearance and high signal-to-background ratio (SBR). Herein, a second near-infrared (NIR-II) fluorescent molecular semiconductor (CDIR2) is synthesized for real-time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post-injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real-time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR-II fluorescent agents.

A Renal-Clearable Duplex Optical Reporter for Real-Time Imaging of Contrast-Induced Acute Kidney Injury.

Despite its high morbidity and mortality, contrast-induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late-stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real-time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near-infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O2.- ) and lysosomal damage (N-acetyl-ß-d-glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O2.- and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier.

A Photolabile Semiconducting Polymer Nanotransducer for Near-Infrared Regulation of CRISPR/Cas9 Gene Editing.

Noninvasive regulation of CRISPR/Cas9 gene editing is conducive to understanding of gene function and development of gene therapy; however, it remains challenging. Herein, a photolabile semiconducting polymer nanotransducer (pSPN) is synthesized to act as the gene vector to deliver CRISPR/Cas9 plasmids into cells and also as the photoregulator to remotely activate gene editing. pSPN comprises a 1 O2 -generating backbone grafted with polyethylenimine brushes through 1 O2 -cleavable linkers. NIR photoirradiation spontaneously triggers the cleavage of gene vectors from pSPN, resulting in the release of CRISPR/Cas9 plasmids and subsequently initiating gene editing. This system affords 15- and 1.8-fold enhancement in repaired gene expression relative to the nonirradiated controls in living cells and mice, respectively. As this approach does not require any specific modifications on biomolecular components, pSPN represents the first generic nanotransducer for in vivo regulation of CRISPR/Cas9 gene editing.

Organic Photodynamic Nanoinhibitor for Synergistic Cancer Therapy.

Despite its great potential in cancer treatment, photodynamic therapy (PDT) often exacerbates hypoxia and subsequently compromises its therapeutic efficacy. To overcome this issue, an organic photodynamic nanoinhibitor (OPNi) has been synthesized that has the additional ability to counteract carbonic anhydrase IX (CA-IX), a molecular target in the hypoxia-mediated signalling cascade. OPNi is composed of a metabolizable semiconducting polymer as the photosensitizer and a CA-IX antagonist conjugated amphiphilic polymer as the matrix. This molecular structure allows OPNi not only to selectively bind CA-IX positive cancer cells to facilitate its tumor accumulation but also to regulate the CA-IX-related pathway. The integration of CA-IX inhibition into the targeted PDT process eventually has a synergistic effect, leading to superior antitumor efficacy over that of PDT alone, as well as the reduced probability of hypoxia-induced cancer metastasis. This study thus proposes a molecular strategy to devise simple yet amplified photosensitizers to conquer the pitfalls of traditional PDT.

Broadband Absorbing Semiconducting Polymer Nanoparticles for Photoacoustic Imaging in Second Near-Infrared Window.

Photoacoustic (PA) imaging holds great promise for preclinical research and clinical practice. However, most studies rely on the laser wavelength in the first near-infrared (NIR) window (NIR-I, 650-950 nm), while few studies have been exploited in the second NIR window (NIR-II, 1000-1700 nm), mainly due to the lack of NIR-II absorbing contrast agents. We herein report the synthesis of a broadband absorbing PA contrast agent based on semiconducting polymer nanoparticles (SPN-II) and apply it for PA imaging in NIR-II window. SPN-II can absorb in both NIR-I and NIR-II regions, providing the feasibility to directly compare PA imaging at 750 nm with that at 1064 nm. Because of the weaker background PA signals from biological tissues in NIR-II window, the signal-to-noise ratio (SNR) of SPN-II resulted PA images at 1064 nm can be 1.4-times higher than that at 750 nm when comparing at the imaging depth of 3 cm. The proof-of-concept application of NIR-II PA imaging is demonstrated in in vivo imaging of brain vasculature in living rats, which showed 1.5-times higher SNR as compared with NIR-I PA imaging. Our study not only introduces the first broadband absorbing organic contrast agent that is applicable for PA imaging in both NIR-I and NIR-II windows but also reveals the advantages of NIR-II over NIR-I in PA imaging.