The heterogeneity of physiological activity for chiral carbon dots derived from L/D/DL-arginine.

Chirality is a ubiquitous phenomenon in nature. The advent of nanomaterials has led to a gradual evolution of chiral studies from the molecular scale to the nanoscale. The emergence of carbon dots (CDs) has inaugurated a novel domain in the scientific and technological realms of carbon nanomaterials. In recent years, CDs have attracted increasing attention due to their luminescent properties, excellent biocompatibility and remarkable bioactivity. However, little attention has been paid to the chirality of the CDs and, in particular, the differences between CDs synthesized from racemic compounds and other chiral CDs, as well as the differences in the biological effects of chiral CDs, remain to be explored. Here, chiral CDs were synthesized from L-/D-/DL-arginine, and the differences in various aspects of chiral CDs were evaluated. We found that L-CDs without extreme differences in structure had brighter fluorescence and a more significant ability of NO generation and lipid droplet inhibition than the other two chiral CDs. Combined with its better drug loading and release ability, we validated its superior efficacy in tumor treatment. Therefore, this study provides a basis for further research on chiral carbon dots and their differences.

Red/NIR-I-Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics.

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L-arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR-I fluorescent carbon dots based on rhein and doped with L-arginine (RA-CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA-CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR-I light for biological imaging. In vitro experiments show that RA-CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS-induced UC mouse model, both delayed and prophylactic treatment with RA-CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small-molecule drugs.

Dual-Emission ZAISe/ZnS quantum dots for Multi-level Bio-Imaging: Foam cells and atherosclerotic plaque imaging.

In vitro or in vivo fluorescence imaging based on quantum dots (QDs) has shown promise for the noninvasive diagnosis of atherosclerosis. However, simultaneous in vitro and in vivo imaging remains challenging due to the limitation of the current synthesis method of dual-emission QDs (dual-emitting hybrid QDs, and broad-spectrum emitting QDs). Herein, we fabricate a dual-emission (visible region and near-infrared region emission) QDs (ZAISe/ZnS) via the "bottom to up" method of a quaternary inorganic compound for the foam cells and atherosclerosis plaque imaging simultaneously without the intricate size modulation and the strict optical filter requirements. The oil-soluble ZAISe/ZnS is further encapsulated with bovine serum albumin (BSA) to realize phase transfer and ultimately possess the inflammation-targeting properties via biomimetic treatment with MMV (macrophage-derived micro-vesicle). The results first indicate that the as-constructed ZAISe/ZnS@BSA@MMV could accurately locate the foam cells and conduct long-term imaging of the atherosclerotic plaque, which provides a new strategy for the early and noninvasive diagnosis of atherosclerosis.

Blood-brain barrier penetrating carbon dots with intrinsic anti-inflammatory and drug-loading properties.

The blood-brain barrier (BBB) is the major obstacle limiting the reach of therapeutic drugs into the brain. Herein, an aspirin-based anti-inflammatory replenisher (aspCD) was fabricated by carbonizing aspirin to deliver drugs into the brain visually. The as-prepared aspCD combined the BBB-penetrating and anti-inflammatory effects of aspirin with the fluorescent and drug-loading properties of carbon dots (CDs), thereby delivering therapeutic drugs into the brain and acting as imaging agent as well as anti-inflammatory replenisher. In vivo experiments of mice and zebrafish revealed that fluorescence aspCD could effectively penetrate BBB. In vitro and in vivo inflammatory models demonstrated that aspCD could be regarded as an excellent anti-inflammatory replenisher. In addition, as a functional carrier, aspCD was proved to be capable of loading drugs with different polarity. In summary, carbonization of active precursors (therapeutic drugs) into CDs could be a promising strategy to achieve the loading and visualization of drugs as well as the retainment of their biological activities.

ZIF-based carbon dots with lysosome-Golgi transport property as visualization platform for deep tumour therapy via hierarchical size/charge dual-transform and transcytosis.

The poor penetration of nanomaterials in solid tumours and difficulty in monitoring their penetration depth are major obstacles in their application for the treatment of solid tumours. Herein, pH-responsive carbon dots (ZCD) based on a zeolitic imidazolate framework (ZIF-8) were fabricated to achieve the deep delivery of the chemotherapeutic doxorubicin (DOX) via a hierarchical size/charge dual-transformation and transcytosis. The as-prepared ZCD accumulated in the solid tumour and the acidic tumour microenvironment further triggered its decomposition. Firstly, ZCD was decomposed by the weakly acidic extracellular microenvironment of the solid tumour, enabling it to transform into small and neutrally charged particles. Subsequently, these particles were endocytosed by lysosomes, and further disintegrated into smaller and positively charged particles, which could target the Golgi apparatus. Consequently, ZCD delivered DOX deep into the solid tumour via a size-shrinking strategy and Golgi-mediated transcytosis, thus significantly improving its antitumour efficacy. In addition, carbonization endowed ZCD with superior fluorescence property, which was enhanced in the acidic microenvironment, thus improving the sensitivity and accuracy of ex vivo monitoring of the penetration depth of the nanomedicine in real time. Collectively, our results confirmed that the carbon dots obtained via the direct carbonization of ZIF-8 simultaneously exhibited enhanced deep penetration into solid tumours and fluorescence, which could be monitored, and that the carbonization of functional materials is effective to enhance their fluorescence, and further broaden their applications.