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.

Effect of homemade peanut oil consumption during pregnancy on low birth weight and preterm birth outcomes: a cohort study in Southwestern China.

BACKGROUND: Homemade peanut oil is widely consumed in rural areas of Southwestern China, which is easily contaminated by aflatoxins (AFs) and associated with adverse birth outcomes. OBJECTIVE: To identify the effect of exposure to homemade peanut oil consumption on low birth weight (LBW), preterm birth (PB) and other associated factors. METHODS: A prospective cohort study was conducted among pregnant women in Guangxi province, Southwestern China. Information of all eligible women on homemade peanut oil consumption and potential factors associated with LBW and PB was collected, and all were followed up until delivery. The effect of homemade peanut oil exposure was analyzed using multiple logistic regression models using the directed acyclic graph (DAG) approach. RESULTS: Of 1611 pregnant women, 1316 (81.7%) had consumed homemade peanut oil, and the rates of LBW and PB were 9.7% and 10.0%, respectively. Increased risks of LBW and PB in women with homemade peanut oil consumption were found with aORs of 1.9 (95% CI 1.1-3.2) and 1.8 (95% CI 1.1-3.0), respectively. Women with a history of PB or LBW were 3-5 times more likely to have higher rates of LBW or PB compared with those without this type of history. The odds of PB were approximately double in those taking medicine during pregnancy. Advanced maternal age, lack of physical exercise during pregnancy, passive smoking, or pregnancy complications were also more likely to have a higher risk of LBW. CONCLUSIONS: Homemade peanut oil consumption was a potential risk factor for both LBW and PB, of which health authorities who are responsible for food safety of the country should pay more attention to providing recommendation for oil consumption during pregnancy.

Main findings: Homemade peanut oil consumption was associated with increased risk of low birth weight and preterm birth, in addition to advanced age, adverse obstetric histories, and health risk behaviors during pregnancy in a county in Southwestern China.Added knowledge: This study identifies the direct and total effects of homemade peanut oil consumption on low birth weight and preterm birth and explains the factors associated with low birth weight and preterm birth in a county in Southwestern China.Global health impact for policy and action: Evidence of associated risk factors for low birth weight and preterm birth should be informed to the community, and precautionary policies for the protection of aflatoxin exposure during pregnancy are needed.

Correlations of Aflatoxin Exposure from Cooking Oil and Dietary Foods During Pregnancy with Birth Weight and Gestational Age at Birth in Guangxi, China.

Background: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth. Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis. Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r ≈0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ -0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth. Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.

The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats.

Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague-Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations.

A construction and empirical research of the journal disruption index based on open citation data.

For many years, the journal evaluation system has been centered on impact indicators, resulting in evaluation results that do not reflect the academic innovation of journals. To solve this issue, this study attempts to construct the Journal Disruption Index (JDI) from the perspective of measuring the disruption of each journal article. In the actual study, we measured the disruption of articles of 22 selected virology journals based on the OpenCitations Index of Crossref open DOI-to-DOI citations (COCI) first. Then we calculated the JDI of 22 virology journals based on the absolute disruption index (DZ) of the articles. Finally, we conducted an empirical study on the differences and correlations between the impact indicators and disruption indicators as well as the evaluation effect of the disruption index. The results of the study show: (1) There are large differences in the ranking of journals based on disruption indicators and impact indicators. Among the 22 journals, 12 are ranked higher by JDI than Cumulative Impact Factor for 5 years (CIF5), the Journal Index for PR6 (JIPR6) and average Percentile in Subject Area (aPSA). The ranking difference of 17 journals between the two kinds of indicators is greater than or equal to 5. (2) There is a medium correlation between disruption indicators and impact indicators at the level of journals and papers. JDI is moderately correlated with CIF5, JIPR6 and aPSA, with correlation coefficients of 0.486, 0.471 and - 0.448, respectively. DZ was also moderately correlated with Cumulative Citation (CC), Percentile Ranking with 6 Classifications (PR6) and Percentile in Subject Area (PSA) with correlation coefficients of 0.593, 0.575 and - 0.593, respectively. (3) Compared with traditional impact indicators, the results of journal disruption evaluation are more consistent with the evaluation results of experts' peer review. JDI reflects the innovation level of journals to a certain extent, which is helpful to promote the evaluation of innovation in sci-tech journals.

Light-Driven Self-Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption.

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off-target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPNP ) is herein reported for precise tumor vascular disruption through two-stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid-derived suppressor cells. Therefore, this study not only illustrates a light-driven self-recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies.

Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics.

Molecular imaging via afterglow luminescence minimizes tissue autofluorescence and increases the signal-to-noise ratio. However, the induction of afterglow requires the prior irradiation of light, which is attenuated by scattering and absorption in tissue. Here we report the development of organic nanoparticles producing ultrasound-induced afterglow, and their proof-of-concept application in cancer immunotheranostics. The 'sonoafterglow' nanoparticles comprise a sonosensitizer acting as an initiator to produce singlet oxygen and subsequently activate a substrate for the emission of afterglow luminescence, which is brighter and detectable at larger tissue depths (4 cm) than previously reported light-induced afterglow. We formulated sonoafterglow nanoparticles containing a singlet-oxygen-cleavable prodrug for the immune-response modifier imiquimod that specifically turn on in the presence of the inflammation biomarker peroxynitrite, which is overproduced by tumour-associated M1-like macrophages. Systemic delivery of the nanoparticles allowed for sonoafterglow-guided treatment of mice bearing subcutaneous breast cancer tumours. The high sensitivity and depth of molecular sonoafterglow imaging may offer advantages for the real-time in vivo monitoring of physiopathological processes.

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.

Second Near-Infrared Light-Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy.

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead to the off-target adverse effects and insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of cancer is reported. ASPA backbone is obtained by conjugating vipadenant, an antagonist to adenosine A2A receptor, onto NIR-II light-absorbing semiconducting polymer via an azo-based thermolabile linker. Under deep-penetrating NIR-II photoirradiation, ASPA induces tumor thermal ablation and subsequently immunogenic cell death, triggers the cleavage of thermolabile linker, and releases the antagonist to block the immunosuppressive adenosinergic pathway. Such a remotely controlled immunometabolic regulation potentiates cytotoxic T cell functions while suppresses regulatory T cell activities, leading to efficient primary tumor inhibition, pulmonary metastasis prevention, and long-term immunological memory. Thereby, this work provides a generic polymeric approach for precise spatiotemporal regulation of cancer immunometabolism.

Urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer.

Aim: Urinary iodine concentration (UIC) may assess radioactive iodine ablation. Materials & methods: According the 2015 American Thyroid Association guidelines, patients were categorized into low- to intermediate-risk or high-risk groups. The iodine concentration in the morning urine specimens was measured by the ceric ion-arsenious acid method. Results: In the low- to intermediate-risk group (113 cases), nonexcellent response (non-ER) was associated with higher UIC, higher UIC subgroups (p < 0.05), higher pre-ablative stimulated thyroglobulin levels (p < 0.01). In the high-risk group (68 cases), the non-ER rate was higher in the higher pre-ablative stimulated thyroglobulin group (p < 0.01), but not significantly different between the UIC and UIC subgroups (p > 0.05). Conclusion: The non-ER rate was related to UIC in the low- to intermediate-risk group; however, UIC did not affect the non-ER rate in the high-risk group.

Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy.

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can remotely generate singlet oxygen (1O2) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPNpro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.

Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer.

Nanomedicine in combination with immunotherapy offers opportunities to treat cancer in a safe and effective manner; however, remote control of immune response with spatiotemporal precision remains challenging. We herein report a photothermally activatable polymeric pro-nanoagonist (APNA) that is specifically regulated by deep-tissue-penetrating second near-infrared (NIR-II) light for combinational photothermal immunotherapy. APNA is constructed from covalent conjugation of an immunostimulant onto a NIR-II semiconducting transducer through a labile thermo-responsive linker. Upon NIR-II photoirradiation, APNA mediates photothermal effect, which not only triggers tumor ablation and immunogenic cell death but also initiates the cleavage of thermolabile linker to liberate caged agonist for in-situ immune activation in deep solid tumor (8 mm). Such controlled immune regulation potentiates systemic antitumor immunity, leading to promoted cytotoxic T lymphocytes and helper T cell infiltration in distal tumor, lung and liver to inhibit cancer metastasis. Thereby, the present work illustrates a generic strategy to prepare pro-immunostimulants for spatiotemporal regulation of cancer nano-immunotherapy.

Diagnostic value of routine ultrasonography combined with ultrasound elastography for papillary thyroid microcarcinoma: A protocol for systematic review and meta-analysis.

BACKGROUND: Papillary thyroid microcarcinoma is easy to be missed because of its small focus, concealed incidence and lack of clinical features. Ultrasound examination is one of the main methods for the detection and diagnosis of papillary thyroid microcarcinoma. The detection rate of conventional ultrasound is not ideal. Combined ultrasound elastography can improve the detection rate, but there is lack of evidence-based evidence. The purpose of this study was to systematically evaluate the value of conventional ultrasound combined with ultrasound elastography in the diagnosis of papillary thyroid microcarcinoma. METHODS: A systematic search was performed by retrieving on English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wanfang, Weipu (VIP), CBM). The retrieval time limit was from the establishment of the database to November 2020 and manually search for the conventional ultrasound combined with ultrasound elastography in the diagnosis of papillary thyroid microcarcinoma. Two researchers extracted and evaluated the quality of the data in the included study independently. A meta-analysis was performed using Meta Disc1.4 and RevMan5.3 software. CONCLUSIONS: This study will evaluate the accuracy and practicability of conventional ultrasound combined with ultrasonic elastography in the diagnosis of papillary thyroid microcarcinoma, and provide evidence-based basis for clinicians to choose the appropriate or best diagnostic method. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. OSF REGISTRATION NUMBER: DOI: 10.17605 / OSF.IO / V6HK7.

A Polymer Multicellular Nanoengager for Synergistic NIR-II Photothermal Immunotherapy.

Cell-membrane-coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second-near-infrared-window (NIR-II) photothermal immunotherapy is reported. The nanoengager consists of an NIR-II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross-interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor-cell-coated nanoparticles. Upon deep-tissue penetrating NIR-II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti-tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell-membrane-coating approach to develop photo-immunotherapeutic agents for cancer therapy.

Second Near-Infrared Photothermal Semiconducting Polymer Nanoadjuvant for Enhanced Cancer Immunotherapy.

Immunotherapy has offered new treatment options for cancer; however, the therapeutic benefits are often modest and desired to be improved. A semiconducting polymer nanoadjuvant (SPNII R) with a photothermally triggered cargo release for second near-infrared (NIR-II) photothermal immunotherapy is reported here. SPNII R consists of a semiconducting polymer nanoparticle core as an NIR-II photothermal converter, which is doped with a toll-like receptor (TLR) agonist as an immunotherapy adjuvant and coated with a thermally responsive lipid shell. Upon NIR-II photoirradiation, SPNII R effectively generates heat not only to ablate tumors and induce immunogenic cell death (ICD), but also to melt the lipid layers for on-demand release of the TLR agonist. The combination of ICD and activation of TLR7/TLR8 enhances the maturation of dendritic cells, which amplifies anti-tumor immune responses. Thus, a single treatment of SPNII R-mediated NIR-II photothermal immunotherapy effectively inhibits growth of both primary and distant tumors and eliminates lung metastasis in a murine mouse model. This study thus provides a remote-controlled smart delivery system to synergize photomedicine with immunotherapy for enhanced cancer treatment.

Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy.

Tumor immunometabolism contributes substantially to tumor proliferation and immune cell activity, and thus plays a crucial role in the efficacy of cancer immunotherapy. Modulation of immunometabolism to boost cancer immunotherapy is mostly based on small-molecule inhibitors, which often encounter the issues of off-target adverse effects, drug resistance, and unsustainable response. In contrast, enzymatic therapeutics can potentially bypass these limitations but has been less exploited. Herein, an organic polymer nanoenzyme (SPNK) with near-infrared (NIR) photoactivatable immunotherapeutic effects is reported for photodynamic immunometabolic therapy. SPNK is composed of a semiconducting polymer core conjugated with kynureninase (KYNase) via PEGylated singlet oxygen (1 O2 ) cleavable linker. Upon NIR photoirradiation, SPNK generates 1 O2 not only to exert photodynamic effect to induce the immunogenic cell death of cancer, but also to unleash KYNase and trigger its activity to degrade the immunosuppressive kynurenine (Kyn). Such a combinational effect mediated by SPNK promotes the proliferation and infiltration of effector T cells, enhances systemic antitumor T cell immunity, and ultimately permits inhibition of both primary and distant tumors in living mice. Therefore, this study provides a promising photodynamic approach toward remotely controlled enzymatic immunomodulation for improved anticancer therapy.

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.

Transformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy.

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.

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.