Jellyfish-inspired smart tetraphenylethene lipids with unique AIE fluorescence, thermal response, and cell membrane interaction.

Smart lipids with fluorescence emission, thermal response, and polyethylene glycolation (PEGylation) functions can be highly valuable for formulation, image-traceable delivery, and targeted release of payloads. Herein, a series of jellyfish-shaped amphiphiles with a tetraphenylethene (TPE) core and four symmetrical amphiphilic side chains were conveniently synthesized and systematically investigated as smart lipids. Compared with regular amphiphilic TPE lipids and phospholipids, the unprecedented jellyfish-shaped molecular geometry was found to enable a series of valuable capabilities, including sensitive and responsive aggregation-induced emission of fluorescence (AIE FL) and real-time FL monitoring of drug uptake. Furthermore, the jellyfish-shaped geometry facilitated the concentration-dependent aggregation from unimolecular micelles at low concentrations to "side-by-side" spherical aggregates at high concentrations and a unique mode of AIE. In addition, the size and the arrangement of the amphiphilic side chains were found to dominate the aggregate stability, cell uptake, and thus the cytotoxicity of the amphiphiles. This study has unprecedentedly developed versatile smart TPE lipids with precise structures, and unique physicochemical and biological properties while the peculiar structure-property relationship may shed new light on the design and application of AIE fluorophores and functional lipids in biomedicine and materials science.

All-in-One Heptamethine Cyanine Amphiphiles for Dual Imaging-Guided Chemo-Photodynamic-Photothermal Therapy of Breast Cancer.

Developing a theranostic system that integrates multimodal imaging, synergistic therapeutic, and formulation entities is a promising strategy for efficient cancer treatment. However, the complexity and safety concerns of multiple functional entities hinder their clinical translation. Herein, versatile "all-in-one" heptamethine cyanine amphiphiles (PEG-Cy-Fs) with multiple favorable capabilities, including fluorine-19 magnetic resonance imaging (19 F MRI), near-infrared fluorescence imaging (NIR FLI), photodynamic therapy (PDT), photothermal therapy (PTT), polyethylene glycolation (PEGylation) and high biocompatibility, are developed for the convenient construction of theranostic platforms. Amphiphiles PEG-Cy-Fs are synthesized on a multi-hundred-milligram scale with high efficacy, which self-assembled with a chemotherapy drug tamoxifen (TAM) into monodisperse and stable nanoparticles (SoFoTm/PEG-Cy-F18 ) with "turned on" FLI, sensitive 19 F MRI, mitochondria-targeting ability, high PDT and PTT efficacy, and PEGylation-optimized pharmacokinetics. The selective accumulation of SoFoTm/PEG-Cy-F18 in xenograft MCF-7 tumor with a long retention time (>10 days) enabled 19 F MRI-NIR FLI-guided chemo-photodynamic-photothermal therapy (chemo-PDT-PTT) of breast cancer with high therapeutical index in mice. The "all-in-one" heptamethine cyanine amphiphile may facilitate the convenient and standardized preparation of high-performance theranostics systems for clinical translation.

One-Pot Synthesis of Monofunctionalized Oligoethylene Glycols through Ring-Opening and Heterogeneous Hydrolysis of Macrocyclic Sulfates.

The one-pot nucleophilic ring-opening reaction of oligoethylene glycol macrocyclic sulfates provides an efficient strategy for the monofunctionalization of oligoethylene glycols without protecting or activating group manipulation. In this strategy, the hydrolysis process is generally promoted by sulfuric acid, which is hazardous, difficult to handle, environmentally unfriendly, and unfit for industrial operation. Here, we explored a convenient handling solid acid, Amberlyst-15, as a replacement for sulfuric acid to accomplish the hydrolysis of sulfate salt intermediates. With this method, 18 valuable oligoethylene glycol derivatives were prepared with high efficiency, and gram-scale applicability of this method has been successfully demonstrated to afford a clickable oligoethylene glycol derivative 1b and a valuable building block 1g for F-19 magnetic resonance imaging traceable biomaterial construction.

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.