Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

Marriage of a Dual-Plasmonic Interface and Optical Microfiber for NIR-II Cancer Theranostics.

The use of light as a powerful tool for disease treatment has introduced a new era in tumor treatment and provided abundant opportunities for light-based tumor theranostics. This work reports a photothermal theranostic fiber integrating cancer detection and therapeutic functions. Its self-heating effect can be tuned at ultralow powers and used for self-heating detection and tumor ablation. The fiber, consisting of a dual-plasmonic nanointerface and an optical microfiber, can be used to distinguish cancer cells from normal cells, quantify cancer cells, perform hyperthermal ablation of cancer cells, and evaluate the ablation efficacy. Its cancer cell ablation rate reaches 89% in a single treatment. In vitro and in vivo studies reveal quick, deep-tissue photonic hyperthermia in the NIR-II window, which can markedly ablate tumors. The marriage of a dual-plasmonic nanointerface and an optical microfiber presents a novel paradigm in photothermal therapy, offering the potential to surmount the challenges posed by limited light penetration depth, nonspecific accumulation in normal tissues, and inadvertent damage in current methods. This work thus provides insight for the exploration of an integrated theranostic platform with simultaneous functions in cancer diagnostics, therapeutics, and postoperative monitoring for future practical applications.

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders.

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet-induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.

Photosensitizer-based small molecule theranostic agents for tumor-targeted monitoring and phototherapy.

Small molecule theranostic agents for tumor treatment exhibited triadic properties in tumor targeting, imaging, and therapy, which have attracted increasing attention as a potential complement for, or improved to, classical small molecule antitumor drugs. Photosensitizer have dual functions of imaging and phototherapy, and have been widely used in the construction of small molecule theranostic agents over the last decade. In this review, we summarized representative agents that have been studied in the field of small molecule theranostic agents based on photosensitizer in the last decade, and highlighted their characteristics and application in tumor-targeted monitoring and phototherapy. The challenges and future perspectives of photosensitizers in building small molecule theranostic agents for diagnosis and therapy of tumors were also discussed.

Phenethoxy Derivatives with Anti-inflammatory Activities from the Betelnut Endophytic Trichoderma asperellum G10.

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).

Optical Microfiber with a Gold Nanorods-Black Phosphorous Nanointerface: An Ultrasensitive Biosensor and Nanotherapy Platform.

The detection and therapy of cancers in the early stage significantly alleviate the associated dangers. Optical devices offer new opportunities for these early measures. However, the clinical translation of the existing methods is severely hindered by their relatively low sensitivity or unclear physiological metabolism. Here, an optical microfiber sensor with a drug loading gold nanorod-black phosphorous nanointerface, as an ultrasensitive biosensor and nanotherapy platform, is developed to meet the early-stage requirement. With interface sensitization and functionalization of the hybrid nanointerface, the microfiber sensor presents an ultrahigh sensing performance, achieving the selective detection of the HER2 biomarker with limits of detection of 0.66 aM in buffer solution and 0.77 aM in 10% serum. It can also distinguish breast cancer cells from other cells in the early stage. Additionally, enabled by the interface, the optical microfiber is able to realize cellular nanotherapy, including photothermal/chemotherapy with pump laser coupling after diagnosis, and evaluate therapy results in real time. The immobilization of the interface on the optical microfiber surface prevents the damage to normal cells induced by nanomaterial enrichment, making the device more efficient and intelligent. This study opens up a new avenue for the development of smart optical platforms for sensitive biosensing and precision therapy.

Single-molecule detection of biomarker and localized cellular photothermal therapy using an optical microfiber with nanointerface.

For early-stage diagnostics, there is a strong demand for sensors that can rapidly detect biomarkers at ultralow concentration or even at the single-molecule level. Compared with other types of sensors, optical microfibers are more convenient for use as point-of-care devices in early-stage diagnostics. However, the relatively low sensitivity strongly hinders their use. To this end, an optical microfiber is functionalized with a plasmonic nanointerface consisting of black phosphorus-supported Au nanohybrids. The microfiber is able to detect epidermal growth factor receptor (ErbB2) at concentrations ranging from 10 zM to 100 nM, with a detection limit of 6.72 zM, enabling detection at the single-molecule level. The nanointerface-sensitized microfiber is capable of differentiating cancer cells from normal cells and treating cancer cells through cellular photothermal therapy. This work opens up a possible approach for the integration of cellular diagnosis and treatment.

Nematicidal amide alkaloids from the seeds of Clausena lansium.

Five new amide alkaloids (1-3, 5-6) were isolated from the seeds of Clausena lansium together with one new natural product (4) and four known analogues (7-10). The structures of the new amide alkaloids were elucidated based on a comprehensive spectroscopic data analysis including 1D and 2D NMR as well as HRESIMS, and by comparison with the literature. The bioactivity results showed that compound 8 expressed potent nematicidal activity against Panagrellus redivevus, with IC50 value of 0.12 mM, while compounds 3 and 5 presented moderate nematicidal activity with IC50 values of 2.75 and 3.93 mM, respectively (abamectin as the positive control with IC50 value of 1.05 mM).

Chrodrimanins O-S from the fungus Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus.

Five new meroterpenoids, chrodrimanins O-S (1-5), as well as a known one (6), were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus, from Haikou Bay, China. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Among them, compound 1 represents the first example of an unusual trichlorinated meroterpenoid with an unique dichlorine functionality. Compounds 1 and 4-6 displayed inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 71.6, 62.5, 63.1, and 39.6µM, respectively, and showed no apparent activity against three tumor cell lines (A549, HepG2, and Hela) and human umbilical vein endothelial cells (HUVEC) at 10µM.