Self-Assembly of Precisely Fluorinated Albumin for Dual Imaging-Guided Synergistic Chemo-Photothermal-Photodynamic Cancer Therapy.

Although albumin has been extensively used in nanomedicine, it is still challenging to fluorinate albumin into fluorine-19 magnetic resonance imaging (19F MRI)-traceable theranostics because existing strategies lead to severe 19F signal splitting, line broadening, and low 19F MRI sensitivity. To this end, 34-cysteine-selectively fluorinated bovine serum albumins (BSAs) with a sharp singlet 19F peak have been developed as 19F MRI-sensitive and self-assembled frameworks for cancer theranostics. It was found that fluorinated albumin with a non-binding fluorocarbon and a long linker is crucial for avoiding 19F signal splitting and line broadening. With the fluorinated BSAs, paclitaxel (PTX) and IR-780 were self-assembled into stable, monodisperse, and multifunctional nanoparticles in a framework-promoted self-emulsion way. The high tumor accumulation, efficient cancer cell uptake, and laser-triggered PTX sharp release of the BSA nanoparticles enabled 19F MRI-near infrared fluorescence imaging (NIR FLI)-guided synergistic chemotherapy (Chemo), photothermal and photodynamic therapy of xenograft MCF-7 cancer with a high therapeutical index in mice. This study developed a rational synthesis of 19F MRI-sensitive albumin and a framework-promoted self-emulsion of multifunctional BSA nanoparticles, which would promote the development of protein-based high-performance biomaterials for imaging, diagnosis, therapy, and beyond.

Photoactivated Nanohybrid for Dual-Nuclei MR/US/PA Multimodal-Guided Photothermal Therapy.

Nanohybrids have gained immense popularity for the diagnosis and chemotherapy of lung cancer for their excellent biocompatibility, biodegradability, and targeting ability. However, most of them suffer from limited imaging information, low tumor-to-background ratios, and multidrug resistance, limiting their potential clinical application. Herein, we engineered a photoresponsive nanohybrid by assembling polypyrrole@bovine serum albumin (PPy@BSA) encapsulating perfluoropentane (PFP)/129Xe for selective magnetic resonance (MR)/ultrasonic (US)/photoacoustic (PA) trimodal imaging and photothermal therapy of lung cancer, overcoming these drawbacks of single imaging modality and chemotherapy. The nanohybrid exhibited superior US, PA, and MR multimodal imaging performance for lung cancer detection. The high sensitivity of the nanohybrid to near-infrared light (NIR) resulted in a rapid increase in temperature in a low-intensity laser state, which initiated the phase transition of liquid PFP into the gas. The ultrasound signal inside the tumor, which is almost zero initially, is dramatically increased. Beyond this, it led to the complete depression of 19F/129Xe Hyper-CEST (chemical exchange saturation transfer) MRI during laser irradiation, which can precisely locate lung cancer. In vitro and in vivo results of the nanohybrid exhibited a successful therapeutic effect on lung cancer. Under the guidance of imaging results, a sound effect of photothermal therapy (PTT) for lung cancer was achieved. We expect this nanohybrid and photosensitive behavior will be helpful as fundamental tools to decipher lung cancer in an earlier stage through trimodality imaging methods.

Triterpenoids with Antiplatelet Aggregation Activity from the Roots of Ilex pubescens.

Two new triterpenes and five new triterpene saponins, named ilexpusons A-G (1-7), as well as eight known compounds were isolated from Ilex pubescens. The structures of the new compounds were established by a combination of chemical and spectroscopic methods, including HRESIMS, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and NOESY. Additionally, the biological activity of compounds 1 - 15 against adenosine diphosphate-induced platelet aggregation in rabbit plasma was determined. Among the tested compounds, 1, 2, 5, 6, 8, 13, 14, and 15 exhibited significant inhibition of platelet aggregation in vitro.

New clerodane diterpenoids from Croton crassifolius.

Two new clerodane diterpenoids (1-2), one new clerodane diterpenoid alkaloid (3), as well as thirteen known compounds were isolated from Croton crassifolius. The structures of new compounds were established by a combination of spectroscopic methods, including HRMS, (1)H NMR, (13)C NMR, (1)H (1)H COSY, HSQC, HMBC, NOESY and X-ray crystallographic analysis. Compound 3 is firstly reported as the clerodane-type diterpenoid alkaloid in natural products. All of the compounds were evaluated for in vitro cytotoxic activities against CT26.WT cell using the MTT method.