Ilicicolin C suppresses the progression of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action.

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy.

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

NIR-II Photoacoustic Imaging-Guided Oxygen Delivery and Controlled Release Improves Photodynamic Therapy for Hepatocellular Carcinoma.

Hypoxia, a prominent hallmark of hepatocellular carcinoma (HCC), undermines curative outcomes, elevates recurrence rates, and fosters metastasis, particularly during photodynamic therapy (PDT) in clinical settings. Studies indicate that alleviating tumor hypoxia enhances PDT efficacy. However, persistent challenges, including suboptimal oxygen delivery efficiency and absence of real-time feedback on blood oxygen fluctuations during PDT, considerably impede therapeutic efficacy in tumor treatment. This study addresses these issues using near-infrared-II (NIR-II) photoacoustic (PA) imaging for tumor-targeted oxygen delivery and controlled release. For this purpose, a biomimetic oxygen delivery system designated BLICP@O2 is developed, which utilizes hybrid tumor cell membranes and thermosensitive liposomes as oxygen carriers, incorporating the NIR-II dye IR1048, photosensitizer chlorin e6 (Ce6), and perfluorohexane. Upon sequential irradiation at 1064 and 690 nm, BLICP@O2 exhibits significant photothermal and photodynamic effects. Photothermal heating triggers oxygen release, enhancing the photodynamic effect of Ce6. Blood oxygen changes during PDT are tracked by multispectral PA imaging. Enhanced PDT efficacy, mediated by hypoxia relief, is convincingly demonstrated both in vitro and in vivo. This work presents an imaging-guided, dual-wavelength programmed cascaded treatment strategy for tumor-targeted oxygen delivery and controlled release, with real-time efficacy monitoring using PA imaging, offering valuable insights for overcoming challenges in PDT-based cancer therapy.

Time - sensitive effects of Zhuang medicated thread moxibustion on estrogen level in female perimenopausal model rats / Efectos sensibles al tiempo de la moxibustión con hilo medicado de Zhuang sobre el nivel de estrógeno en ratas modelo perimenopáusicas hembras

The present study was conducted to ascertain the estrogenic effect of Zhuang Medicated Thread Moxibustion (ZMTM) and explore its time - sensitive impact on estradiol (E2) in female perimenopausal rats. 40 female rats were randomized into four gr oups: the control, model, ZMTM, and acupuncture groups. The perimenopausal syndrome was induced in the last three groups with a daily subcutaneous dose of 80 mg/kg of 4 - vinylcyclohexene diepoxide for 15 days. Afterward, rats in the model and control group s were fed routinely, while rats in the ZMTM and acupuncture groups were treated with six ZMTM and acupuncture courses, respectively. Results of the study suggested that following the six courses of treatment, the E2 level in the model group was significan tly the lowest, while the regular group was the highest (P < 0.05). There was also a gradual increase in the E2 level of the ZMTM group compared to the model and acupuncture groups, e.g. after the 5th and 6th courses of treatment, their E2 level was signif icantly higher than the model and acupuncture groups. The ZMTM group was better than the model and acupuncture groups. In summary, ZMTM can improve perimenopausal induced rats' estrogen level.

El presen te estudio se llevó a cabo para determinar el efecto estrogénico de la moxibustión con hilo medicado Zhuang (ZMTM) y explorar su impacto sensible al tiempo en el estradiol (E2) en ratas hembras perimenopáusicas. Se dividió al azar una muestra de 40 ratas h embras en cuatro grupos: control, modelo, ZMTM y acupuntura. El síndrome perimenopáusico se indujo en los últimos tres grupos con una dosis subcutánea diaria de 80 mg/kg de diepóxido de 4 - vinilciclohexeno durante 15 días. Después, las ratas en los grupos m odelo y control fueron alimentadas rutinariamente, mientras que las ratas en los grupos ZMTM y acupuntura recibieron seis cursos de ZMTM y acupuntura, respectivamente. Los resultados del estudio sugieren que después de los seis cursos de tratamiento, el ni vel de E2 en el grupo modelo fue significativamente más bajo, mientras que el grupo regular fue más alto ( p < 0,05). También hubo un aumento gradual en el nivel de E2 del grupo ZMTM en comparación con los grupos modelo y acupuntura, por ejemplo, desp ués del quinto y sexto cursos de tratamiento, su nivel de E2 fue significativamente más alto que los grupos modelo y acupuntura. El grupo ZMTM fue mejor que los grupos modelo y acupuntura. En resumen, el ZMTM puede mejorar el nivel de estrógeno de las rata s inducidas por la perimenopausia.

Genetically Engineered Biomimetic Nanoparticles for Targeted Delivery of mRNA to Treat Rheumatoid Arthritis.

In addition to inhibiting persistent inflammation, phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is known as an important therapeutic target for alleviating rheumatoid arthritis (RA) symptoms. Modulation of PTEN gene expression in synovial tissue using messenger RNA (mRNA) is a promising approach to combat RA. However, mRNA therapeutics are often hampered by unsatisfactory stability and inefficient localization in synovial tissue. In this study, a genetically engineered biomimetic membrane-coated mRNA (MR@P-mPTEN) carrier that effectively delivers mRNA-PTEN (mPTEN) directly to the RA joint is presented. By overexpressing tumor necrosis factor (TNF-α) receptors on macrophage biomimetic membranes via plasmid transfection, decoys that reduce inflammatory pathway activation are prepared for TNF-α. The resulting construct, MR@P-mPTEN, shows good stability and RA targeting based on in vivo fluorescence imaging. It is also found that MR@P-mPTEN competitively binds TNF-α and activates the PTEN pathway in vitro and in vivo, thereby inhibiting synovitis and joint damage. Clinical micro-computed tomography and histological analyses confirm the treatment effects. These results suggest that the genetically engineered biomimetic therapeutic platform MR@P-mPTEN both inhibits pro-inflammatory cytokines and upregulates PTEN protein expression to alleviate RA damage, providing a new a new combination strategy for RA treatment.

Photoacoustic image-guided biomimetic nanoparticles targeting rheumatoid arthritis.

The high level of reactive oxygen species (ROS) in the rheumatoid arthritis (RA) microenvironment (RAM) and its persistent inflammatory nature can promote damage to joints, bones, and the synovium. Targeting strategies that integrate effective RAM regulation with imaging-based monitoring could lead to improvements in the diagnosis and treatment of RA. Here, we report the combined use of small interfering RNAs (siRNAsT/I) and Prussian blue nanoparticles (PBNPs) to silence the expression of proinflammatory cytokines TNF-α/IL-6 and scavenge the ROS associated with RAM. To enhance the in vitro and in vivo biological stability, biocompatibility, and targeting capability of the siRNAsT/I and PBNPs, macrophage membrane vesicles were used to prepare biomimetic nanoparticles, M@P-siRNAsT/I. The resulting constructs were found to suppress tumor necrosis factor-α/interleukin-6 expression and overcome the hypoxic nature of RAM, thus alleviating RA-induced joint damage in a mouse model. The M@P-siRNAsT/I of this study could be monitored via near-infrared photoacoustic (PA) imaging. Moreover, multispectral PA imaging without the need for labeling permitted the real-time evaluation of M@P-siRNAsT/I as a putative RA treatment. Clinical microcomputed tomography and histological analysis confirmed the effectiveness of the treatment. We thus suggest that macrophage-biomimetic M@P-siRNAsT/I and their analogs assisted by PA imaging could provide a new strategy for RA diagnosis, treatment, and monitoring.

Kaempferol suppresses androgen-dependent and androgen-independent prostate cancer by regulating Ki67 expression.

PURPOSE: Kaempferol is a natural flavonoid that has been reported to be active against many cancers, including prostate cancer, breast cancer and colon cancer. In our previous study, we found kaempferol could act as a selective androgen receptor modulator, thereby suppress development of benign prostatic hyperplasia. This finding inspired us to further explore the effect and the mechanism of action of kaempferol on prostate cancer. METHODS: Plate clone formation assay was performed to detect the effect of kaempferol on cell proliferation. Flow cytometry was used to detect the impact of kaempferol on cell apoptosis and cell cycle distribution. qPCR, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to detect the expression of gene and protein of Ki67 which is a biomarker of cell proliferation. RESULTS: In the present study, we found kaempferol could dramatically suppress androgen-dependent and androgen-independent prostate cancer cells proliferation and induce their apoptosis. Furthermore, we found that kaempferol induced cell cycle to be arrested at G1 phase in 22Rv1 cells but at S and G2 phase in PC-3 cells. In addition, we detected the mRNA and protein of Ki67 which is corresponding to the cell proliferation and found that kaempferol could significantly inhibit Ki67 expression at mRNA level but increase its expression at protein levels in both androgen-dependent and androgen-independent prostate cancer cells. CONCLUSION: Taken together, kaempferol inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cells by regulating the expression of Ki67. These findings further shed light on the mechanism of action of kaempferol on anti-prostate cancer.

Background-suppressed tumor-targeted photoacoustic imaging using bacterial carriers.

Photoacoustic (PA) imaging offers promise for biomedical applications due to its ability to image deep within biological tissues while providing detailed molecular information; however, its detection sensitivity is limited by high background signals that arise from endogenous chromophores. Genetic reporter proteins with photoswitchable properties enable the removal of background signals through the subtraction of PA images for each light-absorbing form. Unfortunately, the application of photoswitchable chromoproteins for tumor-targeted imaging has been hampered by the lack of an effective targeted delivery scheme; that is, photoswitchable probes must be delivered in vivo with high targeting efficiency and specificity. To overcome this limitation, we have developed a tumor-targeting delivery system in which tumor-homing bacteria (Escherichia coli) are exploited as carriers to affect the point-specific delivery of genetically encoded photochromic probes to the tumor area. To improve the efficiency of the desired background suppression, we engineered a phytochrome-based reporter protein (mDrBphP-PCMm/F469W) that displays higher photoswitching contrast than those in the current state of the art. Photoacoustic computed tomography was applied to achieve good depth and resolution in the context of in vivo (mice) imaging. The present system effectively integrates a genetically encoded phytochrome-based reporter protein, PA imaging, and synthetic biology (GPS), to achieve essentially background-suppressed tumor-targeted PA monitoring in deep-seated tissues. The ability to image tumors at substantial depths may enable target-specific cancer diagnoses to be made with greater sensitivity, fidelity, and specificity.

A Near-Infrared Light Triggered Composite Nanoplatform for Synergetic Therapy and Multimodal Tumor Imaging.

Transition-metal chalcogenide compounds with facile preparation and multifunctional elements act as ideal photothermal agents for cancer theranostics. This work synthesizes Cu7.2S4/5MoS2 composite nanoflowers and investigates the crystal growth mechanism to optimize the synthesis strategy and obtain excellent photothermal therapy agents. Cu7.2S4/5MoS2 exhibits a high photothermal conversion efficiency of 58.7% and acts as a theranostic nanoplatform and demonstrated an effective photothermal-chemodynamic-photodynamic synergetic therapeutic effect in both in vitro and in vivo tests. Moreover, Cu7.2S4/5MoS2 shows strong photoacoustic signal amplitudes and computed tomographic contrast enhancement in vivo. These results suggest a potential application of Cu7.2S4/5MoS2 composite nanoflowers as photo/H2O2-responsive therapeutic agents against tumors.

Expanded porphyrins: functional photoacoustic imaging agents that operate in the NIR-II region.

Photoacoustic imaging (PAI) relies on the use of contrast agents with high molar absorptivity in the NIR-I/NIR-II region. Expanded porphyrins, synthetic analogues of natural tetrapyrrolic pigments (e.g. heme and chlorophyll), constitute as potentially attractive platforms due to their NIR-II absorptivity and their ability to respond to stimuli. Here, we evaluate two expanded porphyrins, naphthorosarin (1) and octaphyrin (4), as stimuli responsive PA contrast agents for functional PAI. Both undergo proton-coupled electron transfer to produce species that absorb well in the NIR-II region. Octaphyrin (4) was successfully encapsulated into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) nanoparticles to afford OctaNPs. In combination with PAI, OctaNPs allowed changes in the acidic environment of the stomach to be visualized and cancerous versus healthy tissues to be discriminated.

Notch-1 and Notch-3 Mediate Hypoxia-Induced Activation of Synovial Fibroblasts in Rheumatoid Arthritis.

OBJECTIVE: To investigate the molecular mechanism of hypoxia-induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch-1 and Notch-3 signaling, and to evaluate its potential as a therapeutic target. METHODS: Expression of Notch-1 intracellular domain (N1ICD), N3ICD, and hypoxia-inducible factor 1α (HIF-1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen-induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. RESULTS: N1ICD, N3ICD, and HIF-1α were expressed abundantly in the synovial tissue of RA patients. HIF-1α was shown to directly regulate the expression of Notch-1 and Notch-3 genes under hypoxic conditions. Moreover, hypoxia-induced N1ICD and N3ICD expression in RASFs was blocked by HIF-1α siRNA. Notch-1 siRNA and Notch-3 siRNA inhibited hypoxia-induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch-1 was shown to regulate RASF migration and epithelial-mesenchymal transition under hypoxic conditions, whereas Notch-3 was shown to regulate the processes of anti-apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. CONCLUSION: This study identified a functional link between HIF-1α, Notch-1, and Notch-3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.

Opto-acoustic synergistic irradiation for vaporization of natural melanin-cored nanodroplets at safe energy levels and efficient sono-chemo-photothermal cancer therapy.

Rationale: Insufficient penetration and accumulation of theranostic payloads in solid tumors greatly challenge the clinical translation of cancer nanomedicines. To address this challenge, we synthesized natural melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets with good biocompatibility and self-assembling ability. Methods: We used an opto-acoustic synergistic irradiation (OASI) method that was effective at lower energy levels than ultrasound- or laser-only irradiation to safely vaporize the nanodroplets and to cavitate the generated microbubbles for mechanically enhancing intratumoral delivery. The delivered melanin and doxorubicin inside the tumors mediated secondary chemo-photothermal therapy under laser irradiation to fully kill cancer cells. Results:In vivo animal experiments demonstrated direct mechanical disruption of tumor structures (H&E staining), enhanced intratumoral penetration of melanin (photoacoustic imaging), and efficient intratumoral accumulation of doxorubicin (fluorescent imaging). Anti-tumor experiments demonstrated that the nanodroplets combined with OASI treatment and subsequent laser irradiation could efficiently eliminate melanoma tumors. Conclusion: Melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets hold great promise for translational sono-chemo-photothermal cancer therapy.

Manganese(II) Texaphyrin: A Paramagnetic Photoacoustic Contrast Agent Activated by Near-IR Light.

The NIR absorptivity of the metallotexaphyrin derivatives MMn, MGd, and MLu for photoacoustic (PA)-based imaging is explored in this study. All three complexes demonstrated excellent photostabilities; however, MMn provided the greatest PA signal intensities in both doubly distilled water and RAW 264.7 cells. In vivo experiments using a prostate tumor mouse model were performed. MMn displayed no adverse toxicity to major organs as inferred from hematoxylin and eosin (H&E) staining and cell blood count testing. MMn also allowed for PA-based imaging of tumors with excellent in vivo stability to provide 3D tumor diagnostic information. Based on the present findings and previous magnetic resonance imaging (MRI) studies, we believe MMn may have a role to play either as a stand-alone PA contrast agent or as a single molecule dual modal (PA and MR) imaging agent for tumor diagnosis.

Novel small molecular dye-loaded lipid nanoparticles with efficient near-infrared-II absorption for photoacoustic imaging and photothermal therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is the second leading cause of mortality in cancer patients. Thus, accurate diagnosis and effective treatment of the malignancy is very critical for HCC patients. The photoacoustic (PA) nanoparticle with ultra-sensitive imaging signals and high photothermal conversion efficacy is a new and promising method for achieving the desired goals. In this study, we have synthesized a novel lipid nanoparticle based on IR-1061 dyes by encapsulating the dye into a liposome which was modified by DSPE-PEG2000. We conducted serial experiments to investigate the PA diagnosis performance, the surgical navigation, and the photothermal therapy (PTT) capability of the novel nanoparticle (Polipo-IR NP) in nude mice bearing HCC. The results showed that our novel nanoparticles exhibited strong laser energy absorption at 1064 nm wavelength, high photothermal conversion efficacy (45.25%) and ultra-sensitive PA signals. The in vivo PA studies demonstrated that the proposed nanoparticles could diagnose tumors non-invasively and accurately with a strong signal-to-noise ratio of 5.98 ± 0.23 at 3 h post-injection and could successfully achieve radical resection of tumors intraoperatively. Furthermore, the PTT test demonstrated a remarkable cancer cell killing ability because of its high photothermal conversion efficacy. The excellent photostability and high biocompatibility were also validated by in vitro and in vivo experiments. Thus, our proposed NIR-II PA and PTT nanoparticles based on the IR-1061 dye would potentially provide novel insights into understanding polymethine dyes in nanomedicine and would greatly benefit early diagnosis and treatment of HCC patients.

High-Resolution 3D NIR-II Photoacoustic Imaging of Cerebral and Tumor Vasculatures Using Conjugated Polymer Nanoparticles as Contrast Agent.

Exogenous contrast-agent-assisted NIR-II optical-resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide-field 3D biological structures with deep penetration, large signal-to-background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR-II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g-1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL-1 . 3D ORPAMI of wide-field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole-cortex cerebral vasculatures with large imaging area (48 mm2 ), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR-II fluorescence confocal vascular imaging, which opens up new opportunities for NIR-II CP-NP-assisted ORPAMI in various biomedical applications.

A 1064 nm excitable semiconducting polymer nanoparticle for photoacoustic imaging of gliomas.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (especially at 1064 nm) has the benefits of low background signal, high spatial resolution and deep tissue penetration. Here we report a semiconducting polymer nanoparticle (PDPPTBZ NP) and demonstrate its potential as a contrast agent for PA imaging of orthotopic brain tumors, using a 1064 nm pulsed laser as a light source. PDPPTBZ NPs have maximum absorption at 1064 nm with a mass extinction coefficient of 43 mL mg-1 cm-1, which is the highest value reported so far in this region. The high photothermal conversion efficiency (67%) and near non-fluorescence impart PDPPTBZ NPs with excellent PA properties. We used PDPPTBZ NP-containing agar gel phantoms even at a low concentration (50 µg mL-1) to successfully image to a depth of 4 cm (of chicken-breast tissue), with an ultralow power fluence (4 mJ cm-2). Furthermore, we could clearly visualize a glioma tumor in a mouse at a depth of 3.8 mm below the skull. This study demonstrates that PDPPTBZ NPs display great potential as a NIR-II PA contrast agent for high quality deep tissue imaging.

Ce6-Modified Carbon Dots for Multimodal-Imaging-Guided and Single-NIR-Laser-Triggered Photothermal/Photodynamic Synergistic Cancer Therapy by Reduced Irradiation Power.

Photomediated cancer therapy, mainly including photothermal (PT) therapy (PTT) and photodynamic therapy (PDT), has attracted tremendous attention in recent years thanks to its noninvasive and stimuli-responsive features. The single mode of PTT or PDT, however, has obvious drawbacks, either requiring high-power laser irradiation to generate enough heat or only providing limited efficacy due to the hypoxia nature inside tumors. In addition, the reported synergistic PTT/PDT generally utilized two excitation sources to separately activate PTT and PDT, and the problem of high-power laser irradiation for PTT was still not well solved. Herein, a new concept, loading a small amount of photosensitizers onto a PTT agent (both of them can be triggered by a single-near-infrared (NIR) laser), was proposed to evade the shortcomings of PTT and PDT. To validate this idea, minute quantities of photosensitizer chlorin e6 (Ce6) (0.56% of mass) were anchored onto amino-rich red emissive carbon dots (RCDs) that possess superior photothermal (PT) character under 671 nm NIR laser (PT conversion efficiency to be 46%), and meanwhile the PDT of Ce6 can be activated by this laser irradiation as well. The findings demonstrate that Ce6-modified RCDs (named Ce6-RCDs) offer much higher cancer therapy efficacy under a reduced laser power density (i.e., 0.50 W cm-2 at 671 nm) in vitro and in vivo than the equivalent RCDs or Ce6 under the same irradiation conditions. Besides, the Ce6-RCDs also exhibit multimodal imaging capabilities (i.e., fluorescence (FL), photoacoustic (PA), and PT), which can be employed for guidance of the phototherapy process. This study suggests not only a strategy to enhance cancer phototherapy efficacy but also a promising candidate (i.e., Ce6-RCDs) for multimodal FL/PA/PT imaging-guided and single-NIR-laser-triggered synergistic PTT/PDT for cancers by a reduced irradiation power.

In Vivo Tumor Photoacoustic Imaging and Photothermal Therapy Based on Supra-(Carbon Nanodots).

Carbon nanodots (CNDs) with high photothermal conversion efficiency are considered as emerging nanomaterials for advanced biomedical applications attributing to their high biocompatibility, low-cost, and unique photophysical properties. In previous work, supra-CNDs are synthesized exhibiting high absorption in the near-infrared (NIR) region and good NIR photothermal conversion performance. In this work, supra-CNDs are explored as a photothermal agent for photothermal therapy (PTT) and a contrast agent for photoacoustic (PA) imaging, respectively. As a result, in vivo tumor PTT is realized under 655 nm laser irradiation via intratumor injecting supra-CNDs. In vivo PA imaging reveals that supra-CNDs can accumulate in the tumor tissue via the blood circulation after intravenous injection. Moreover, in vivo PTT is conducted after intravenous injection and subsequent tumor accumulation of supra-CNDs, and the lives of mice are prolonged due to the tumor growth inhibition after PTT. These attractive properties indicate that the supra-CNDs can be used as biomedical agents for PA imaging and tumor therapy.

Highly Sensitive MoS2-Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site.

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS2-ICG hybrid with indocyanine green (ICG) conjugated to the surface of MoS2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS2-ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS2-ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.