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.

Near-Infrared-II Activatable Symbiotic 2D Carbon-Clay Nanohybrids for Dual Imaging-Guided Combinational Cancer Therapy.

Two-dimensional (2D) nanomaterials hold great potential for cancer theranostic applications, yet their clinical translation faces great challenges of high toxicity and limited therapeutic/diagnostic modality. Here, we have created a kind of symbiotic 2D carbon-2D clay nanohybrids, which are composed of a novel 2D carbon nanomaterial (carbon nanochips, or CNC), prepared by carbonizing a conjugated polymer polydiiodobutadiyne, and a 2D layered aluminosilicate clay mineral montmorillonite (MMT). Intriguingly, with the formation of the nanohybrids, MMT can help the dispersion of CNC, while CNC can significantly reduce the hemolysis and toxicity of MMT. The symbiotic combination of CNC and MMT also leads to a synergistic anti-cancer theranostic effect. CNC has a strong absorption and high photothermal conversion efficiency in the second near-infrared region (NIR-II, 1000-1700 nm), while MMT contains Fe3+ that can facilitate the generation of reactive oxygen species from highly expressed H2O2 in tumor microenvironment. The nanohybrids not only enable a synergy of photothermal therapy and chemodynamic therapy to suppress the extremely rapid growth of RM1 tumors in mice but also allow for dual photoacoustic and magnetic imaging to guide the drug delivery and NIR-II irradiation execution, hence establishing a highly efficient and biosafe "all-in-one" theranostic platform for precision nanomedicine.

Degradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics.

Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed Sb2O3. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.

Dedicated Photoacoustic Imaging Instrument for Human Periphery Blood Vessels: A New Paradigm for Understanding the Vascular Health.

A novel photoacoustic imaging system based on a semi-ring transducer array is proposed to image peripheral blood vessels. The system's penetration depth is deep (∼15 mm) with high spatial (∼200 µm) and temporal resolution. In a clinical study, volumetric photoacoustic data of limbs were obtained within the 50s (for a FOV of 15 cm × 4 cm) with the volunteers in the standing and sitting posture. Compared to the previous studies, our system has many advantages, including (1) Larger field of view; (2) Finer elevational and in-plane resolutions; (3) Enhanced 3D visualization of peripheral vascular networks; (4) Compact size and better portability. The 3D visualization and cross-sectional images of five healthy volunteers clearly show the vascular network and the system's ability to image submillimeter blood vessels. This high-resolution PA system has great potential for imaging human periphery vasculatures noninvasively in clinical research.

Co-delivery of NIR-II semiconducting polymer and pH-sensitive doxorubicin-conjugated prodrug for photothermal/chemotherapy.

Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm2 for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo. Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. STATEMENT OF SIGNIFICANCE: Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo.

[Photoacoustic imaging study on spatial structure of microvessels around acupoints in mice with acute myocardial ischemia].

OBJECTIVE: To observe the changes of microvascular structure of acupoints caused by myocardial ischemia, so as to explore the application of photoacoustic imaging technology in the research of acupoint sensitization. METHODS: Twelve BALB/c mice were randomly divided into normal, sham operation and acute myocardial ischemia (AMI) model groups, with 4 mice in each group. AMI model was established by ligating the left anterior descending coronary artery. Electrocardiogram (ECG) was recorded by physiological signal acquisition system at 12 h and on the 14th day after modeling, and serum cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB) levels were detected by enzyme-linked immunosorbent assay. The microvascular structure changes of acupoints "Feishu"(BL13), "Jueyinshu"(BL14), "Quze"(PC3) and "Chize"(LU5) were observed by photoacoustic imaging technology, and distance (DM), inflection count metric (ICM), sum of angle metric(SOAM)and microvessel density (MVD) were calculated by microvascular quantification algorithm. RESULTS: Compared with the normal and sham operation groups, the ST segment of ECG was obviously elevated, serum cTnT and CK-MB were significantly increased in AMI model group at 12 h and on the 14th day after AMI (P<0.01). The ICM of BL14 in AMI model group was significantly decreased on the 14th day than that on the 7th day after AMI. Compared with the normal group, the ICM of BL14 was significantly increased in AMI model group on the 7th day after AMI(P<0.05). There were no significant changes in DM, ICM, SOAM and MVD at other acupoints on the 7th and 14th day (P>0.05) among the three groups. CONCLUSION: The change of ICM may be one of the characteristics of acupoint sensitization and photoacoustic imaging technology can be used to study the structure of acupoint microvessels.

Antimony Nanopolyhedrons with Tunable Localized Surface Plasmon Resonances for Highly Effective Photoacoustic-Imaging-Guided Synergistic Photothermal/Immunotherapy.

Antimony (Sb), a typical group VA semimetal, has rarely been studied both experimentally and theoretically in plasmonic photothermal therapy, possibly due to the lack of effective morphology-controllable methods for the preparation of high-quality Sb nanocrystals. In this study, an effective ligand-guided growth strategy to controllably synthesize Sb nanopolyhedrons (Sb NPHs) with ultrahigh photothermal conversion efficiency (PTCE), good photothermal stability, as well as biocompatibility is presented. Furthermore, the modulation effect of different morphologies on localized surface plasmon resonance (LSPR) of Sb NPHs in experimentation is successfully observed. When the resonance frequency of the Sb NPHs is matched well with the excitation wavelength (808 nm), the PTCE of the Sb NPHs is as high as 62.1%, which is noticeably higher compared to most of the reported photothermal agents. The Sb NPHs also exhibit good photothermal stability. In addition, Sb-NPHs-based multifunctional nanomedicines are further constructed via loading 1-methyl-d-tryptophan on PEGylated Sb NPHs for a highly efficient photoacoustic-imaging-guided synergistic photothermal/immune-therapy of tumors in vivo. This work can stimulate further theoretical and experimental investigations of Sb NPHs and other semimetal nanomaterials regarding their LSPR properties and inspire various potential applications of semimetals in biomedicine and sensors.

Active-Targeting NIR-II Phototheranostics in Multiple Tumor Models Using Platelet-Camouflaged Nanoprobes.

Cancer phototheranostics in the second near-infrared window (NIR-II, 1000-1700 nm) has recently attracted much attention owing to its high efficacy and good safety compared with that in the first near-infrared window (NIR-I, 650-950 nm). However, the lack of theranostic nanoagents with active-targeting features limits its further application in cancer precision therapies. Herein, we constructed platelet-camouflaged nanoprobes with active-targeting characteristics for NIR-II cancer phototheranostics. The as-prepared biomimetic nanoprobes can not only escape phagocytosis by macrophages but also specifically bind to CD44 on the surface of most cancer cells. We evaluated the active-targeting performance of biomimetic nanoprobes in pancreatic cancer, breast cancer, and glioma mouse models and achieved NIR-II photoacoustic imaging with a high signal-to-background ratio and photothermal treatment with excellent tumor growth inhibition. Our results show the great potential of platelet-camouflaged nanoprobes with NIR-II active-targeting features for cancer precision diagnosis and efficient therapies.

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.

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.

Lack of association between acupoint sensitization and microcirculatory structural changes in a mouse model of knee osteoarthritis: A pilot study.

As a stimulating point in acupuncture, acupoint has unique microcirculatory features, and its dynamics vary greatly depending on health status. Acupoint sensitization is defined as the transformation of an acupoint from a "silenced status" (healthy) to an "activated status" (disease). Our previous study demonstrated that acupoint sensitization is associated with an increase in the level of local blood perfusion. However, the structural changes in microcirculation during acupoint sensitization have yet to be elucidated because the high-resolution microcirculation imaging of acupoints has been difficult to obtain. In this study, the structural changes in microcirculation at the Zusanli (ST36), Yanglingquan (GB34) and nonacupoint sites on days 0, 7 and 21 were dynamically observed during acupoint sensitization in an experimental knee osteoarthritis mouse model by using optical-resolution photoacoustic microscopy. The results showed that no significant differences in microvessel density, the distribution of vessel diameters or vascular tortuosity were observed at the GB34, ST36 or nonacupoint sites among days 0, 7 and 21. We proposed that acupoint sensitization may not be associated with the structural changes in microcirculation and that the microcirculatory changes during acupoint sensitization are more likely to be functional. The functional characteristics of the sensitized acupoints warrant further investigation.

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.

Through Scalp and Skull NIR-II Photothermal Therapy of Deep Orthotopic Brain Tumors with Precise Photoacoustic Imaging Guidance.

Brain tumor is one of the most lethal cancers owing to the existence of blood-brain barrier and blood-brain tumor barrier as well as the lack of highly effective brain tumor treatment paradigms. Herein, cyclo(Arg-Gly-Asp-D-Phe-Lys(mpa)) decorated biocompatible and photostable conjugated polymer nanoparticles with strong absorption in the second near-infrared (NIR-II) window are developed for precise photoacoustic imaging and spatiotemporal photothermal therapy of brain tumor through scalp and skull. Evidenced by the higher efficiency to penetrate scalp and skull for 1064 nm laser as compared to common 808 nm laser, NIR-II brain-tumor photothermal therapy is highly effective. In addition, via a real-time photoacoustic imaging system, the nanoparticles assist clear pinpointing of glioma at a depth of almost 3 mm through scalp and skull with an ultrahigh signal-to-background ratio of 90. After spatiotemporal photothermal treatment, the tumor progression is effectively inhibited and the survival spans of mice are significantly extended. This study demonstrates that NIR-II conjugated polymer nanoparticles are promising for precise imaging and treatment of brain tumors.

Hybrid MoSe2-indocyanine green nanosheets as a highly efficient phototheranostic agent for photoacoustic imaging guided photothermal cancer therapy.

Phototheranostic technology based on photoacoustic imaging (PAI) and photothermal therapy (PTT) is emerging as a powerful tool for tumor theranostic applications. For effective tumor eradication, a novel PAI/PTT theranostic nanoagent with an excellent optical absorption and photothermal capability is highly desired. Herein, we present a new PAI/PTT nanohybrid named sMoSe2-ICG NSs by covalently conjugating aminated indocyanine green (ICG) onto a single layer of molybdenum selenide nanosheets (sMoSe2 NSs). We first validate the sMoSe2-ICG NS agent for the PAI and PTT effect in vitro and then use it for highly-sensitive PAI guided highly efficient tumor PTT in vivo. The sMoSe2-ICG NS hybrid possesses several advantages for PAI/PTT applications: (1) the sMoSe2-ICG NSs have strong absorbance in the broad near-infrared (NIR) region, enabling a highly efficient PAI/PTT theranostic effect and the selection of the most widely used excitation wavelength of 808 nm for PTT; (2) the photothermal ability of ICG in sMoSe2-ICG NSs is augmented due to ICG aggregation induced fluorescence quenching and the re-absorbance of ICG fluorescence by sMoSe2 NSs, which further enhances the PAI/PTT theranostic effect. (3) The characteristic absorption peak of sMoSe2-ICG NSs is red-shifted compared to free ICG, resulting in a higher PAI signal-to-noise ratio (SNR) in vivo. Thus, combined with the good stability, high biocompatibility and minimal toxicity properties, the obtained sMoSe2-ICG NSs hybrid has bright prospects for use in future PAI/PTT clinical applications.

Förster Resonance Energy Transfer-Based Dual-Modal Theranostic Nanoprobe for In Situ Visualization of Cancer Photothermal Therapy.

The visualization of the treatment process in situ could facilitate to accurately monitor cancer photothermal therapy (PTT), and dramatically decrease the risk of thermal damage to normal cells and tissues, which represents a major challenge for cancer precision therapy. Herein, we prepare theranostic nanoprobes (NPs) for Förster resonance energy transfer (FRET)-based dual-modal imaging-guided cancer PTT, and clear visualization of the therapeutic process. The FRET-based theranostic NPs exhibit high FRET efficiency (88.2%), good colloidal stability, and tumor-targeting ability. Tumor tissue and surrounding blood vessels are visualized clearly by FRET-based NIR fluorescence imaging with a high signal-to-background ratio (14.5) and photoacoustic imaging with an excellent resolution at 24 h post injection of NPs. Under the guidance of dual-modal imaging, the NPs-induced photothermal effect selectively destructs cancer cells, simultaneously decreasing the FRET efficiency and leading to fluorescence and photoacoustic signal changes. The sensitive self-feedback process enables the in situ visualization of therapeutic process and precision guidance of in vivo cancer PTT. A high therapeutic efficacy and minimum side effects are achieved in C6 tumor-bearing nude mice, holding great promise for precision therapy and cancer theranostics.

Molecular Engineering of Conjugated Polymers for Biocompatible Organic Nanoparticles with Highly Efficient Photoacoustic and Photothermal Performance in Cancer Theranostics.

Conjugated polymer nanoparticles (CP NPs) are emerging candidates of "all-in-one" theranostic nanoplatforms with dual photoacoustic imaging (PA) and photothermal therapy (PTT) functions. So far, very limited molecular design guidelines have been developed for achieving CPs with highly efficient PA and PTT performance. Herein, by designing CP1, CP2, and CP3 using different electron acceptors (A) and a planar electron donor (D), we demonstrate how the D-A strength affects their absorption, emission, extinction coefficient, and ultimately PA and PTT performance. The resultant CP NPs have strong PA signals with high photothermal conversion efficiencies and excellent biocompatibility in vitro and in vivo. The CP3 NPs show a high PA signal to background ratio of 47 in U87 tumor-bearing mice, which is superior to other reported PA/PTT theranostic agents. A very small IC50 value of 0.88 µg/mL (CP3 NPs) was obtained for U87 glioma cell ablation under laser irradiation (808 nm, 0.8 W/cm2, 5 min). This study shows that CP NP based theranostic platforms are promising for future personalized nanomedicine.

Vitamin D Enhances Alveolar Development in Antenatal Lipopolysaccharide-Treated Rats through the Suppression of Interferon-γ Production.

Bronchopulmonary dysplasia (BPD) is characterized by the premature arrest of alveolar development. Antenatal exposure to inflammation inhibits lung morphogenesis, thereby increasing the risk for the development of BPD. Here, we investigated whether vitamin D (VitD) enhances alveolar development in antenatal lipopolysaccharide (LPS)-treated rats, which is a model for BPD. We used an established animal model of BPD, and random assignment to the control group, LPS group, or LPS with VitD group. Levels of interferon (IFN)-γ and interleukin-4 were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. IFN-γ producing CD8+ T cells were assessed by flow cytometry, and the methylation status of the VitD-response element (VDRE) was analyzed by bisulfite sequencing PCR. 25-hydroxyvitamin D levels were measured by liquid chromatography tandem mass spectrometry in maternal serum samples collected from 86 pregnant women in a prospective birth cohort enrolled from 2012 to 2013. Our results showed that VitD effectively alleviated the simplification of the lung alveolar structure in BPD rats and suppressed LPS-induced IFN-γ expression in the lung and spleen tissues. Further investigation revealed that VitD suppressed IFN-γ production in CD8+ T cells. Specifically, VitD increased the methylation percentage of the VDRE in the IFN-γ-promoter region and suppressed LPS-induced expression of IFN-γ. Additionally, we observed an association between maternal VitD exposure during pregnancy and neonatal IFN-γ levels in a prospective birth cohort, with a trend similar to that observed in the animal model. Our data suggested that supplementation of VitD could suppress IFN-γ production, resulting in improved alveolar development in an LPS-induced BPD rat model.

Indocyanine green-loaded polydopamine-iron ions coordination nanoparticles for photoacoustic/magnetic resonance dual-modal imaging-guided cancer photothermal therapy.

Multi-modal imaging-guided cancer photothermal therapy (PTT) with advanced theranostic nanoagents can efficiently improve therapeutic efficacy and reduce treatment side effects. Herein, we have developed a theranostic nanoagent based on indocyanine green (ICG)-loaded polydopamine (PDA)-iron ions coordination nanoparticles (PDA-Fe3+-ICG NPs), which are used for photoacoustic (PA) and magnetic resonance (MR) dual-modal imaging-guided cancer PTT treatments. In this nanoplatform, ICG molecules, the U.S. Food and Drug Administration approved near-infrared (NIR) dye, absorbing on PDA NPs (a melanin-like biopolymer) to significantly increase the NIR optical absorption of PDA NPs nearly 6 times and decreases their fluorescence emission, which can improve the PA contrast ability and promote the photothermal conversion efficiency of PDA NPs. Meanwhile, Fe3+ ions chelated on the PDA NPs act as a T1-weighted MRI contrast agent (r1 = 14 mM-1 s-1). In a mouse 4T1 breast tumor model, PA/MRI dual-modal imaging and highly efficient PTT treatments with low laser density were achieved with remarkable therapeutic efficiency and minimal side effects. This study illustrates that the highly integrated and biocompatible PDA-based NPs can serve as a versatile nanoplatform by loading different imaging molecules and drugs for multi-modal imaging and cancer combination therapy.

A facile synthesis of versatile Cu2-xS nanoprobe for enhanced MRI and infrared thermal/photoacoustic multimodal imaging.

A novel type of intelligent nanoprobe by using single component of Cu2-xS for multimodal imaging has been facilely and rapidly synthesized in scale via thermal decomposition followed by biomimetic phospholipid modification, which endows them with uniform and small nanoparticle size (ca.15 nm), well phosphate buffer saline (PBS) dispersity, high stability, and excellent biocompatibility. The as-synthesized Cu2-xS nanoprobes (Cu2-xS NPs) are capable of providing contrast enhancement for T1-weighted magnetic resonance imaging (MRI), as demonstrated by the both in vitro and in vivo imaging investigations for the first time. In addition, due to their strong near infrared (NIR) optical absorption, they can also serve as a candidate contrast agent for enhanced infrared thermal/photoacoustic imaging, to meet the shortfalls of MRI. Hence, complementary and potentially more comprehensive information can be acquired for the early detection and accurate diagnosis of cancer. Furthermore, negligible systematic side effects to the blood and tissue were observed in a relatively long period of 3 months. The distinctive multimodal imaging capability with excellent hemo/histocompatibility of the Cu2-xS NPs could open up a new molecular imaging possibility for detecting and diagnosing cancer or other diseases in the future.