Because of their unique advantages, fluorescent carbon dots are gaining popularity in various biomedical applications. For these applications, good biosafety is a prerequisite for their use in vivo. Studies have reported the preliminary biocompatibility evaluations of fluorescent carbon dots (mainly cytotoxicity); however, to date, little information is available about their hemocompatibility, which could impede their development from laboratory to bedside. In this work, we evaluated the hemocompatibility of fluorescent carbon dots, which we prepared by hydrothermal carbonization of α-cyclodextrin. The effects of the carbon dots on the structure and function of key blood components were investigated at cellular and molecular levels. In particular, we considered the morphology and lysis of human red blood cells, the structure and conformation of the plasma protein fibrinogen, the complement activation, platelet activation, and in vitro and in vivo blood coagulation. We found that the carbon dots have obvious concentration-dependent effects on the blood components. Overall, concentrations of the fluorescent carbon dots at ≤0.1 mg/mL had few adverse effects on the blood components, but at higher doses, the carbon dots impair the structure and function of the blood components, causing morphological disruptions and lysis of red blood cells, interference in the local microenvironments of fibrinogen, activation of the complement system, and disturbances in the plasma and whole blood coagulation function in vitro. However, the carbon dots tend to activate platelets only at low concentrations. Intravenous administration of the carbon dots at doses up to 50 mg/kg did not impair the blood coagulation function. These results provide valuable information for the clinical application of fluorescent carbon dots.

A novel star-shaped polymer, porphyrin-poly(L-lysine) dendrons (PP-PLLD), is synthesized by the click reaction between azido-modified porphyrin and propargyl focal point poly(L-lysine) dendrons. Its chemical structure is characterized by (1) H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and gel permeation chromatography (GPC) is analyses etc. Due to its amphiphilic property, the obtained PP-PLLD has a low critical micelle concentration in an aqueous solution, and can load doxorubicin (DOX) with a loading amount of 64 μg mg(-1) . By in vitro toxicity assay, PP-PLLD has no dark cytotoxicity but has significant phototoxicity. Moreover, DOX-loaded PP-PLLD shows a higher cytotoxicity under the light condition than PP-PLLD or DOX alone, suggesting PP-PLLD has a potential application in combined photodynamic therapy and chemotherapy.

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The expression of plastid genes is regulated by two types of DNA-dependent RNA polymerases, plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA polymerase (NEP). The plastid rpoA polycistron encodes a series of essential chloroplast ribosome subunits and a core subunit of PEP. Despite the functional importance, little is known about the regulation of rpoA polycistron. In this work, we show that mTERF6 directly associates with a 3′-end sequence of rpoA polycistron in vitro and in vivo, and that absence of mTERF6 promotes read-through transcription at this site, indicating that mTERF6 acts as a factor required for termination of plastid genes’ transcription in vivo. In addition, the transcriptions of some essential ribosome subunits encoded by rpoA polycistron and PEP-dependent plastid genes are reduced in the mterf6 knockout mutant. RpoA, a PEP core subunit, accumulates to about 50% that of the wild type in the mutant, where early chloroplast development is impaired. Overall, our functional analyses of mTERF6 provide evidence that it is more likely a factor required for transcription termination of rpoA polycistron, which is essential for chloroplast gene expression and chloroplast development.

Imaging-guided stimuli-responsive delivery systems based on nanomaterials for cancer theranostics have been recognized as promising alternatives to traditional therapies in clinic. How to integrate multiple response-mediated nanoproperty (i.e., charge, size, or stability) transitions into a cascaded manner to overcome multistage biological barriers which usually demand different and even opposing nanoproperties in each stage is still a challenge. Herein, a multistage and cascaded responsive theranostic nanoplatform for imaging-traceable TRAIL gene precise delivery was prepared by a cleavable PEGylated shell and a fluorescent carbon dot (CD)-based core. The CDs as the core were prefunctionalized with polyethylenimine end-capped disulfide-bond-bearing hyperbranched poly­(amido amine) (HPAP), endowing the CDs with enhanced fluorescent quantum yield (27%), intracellular degradability, and efficient gene delivery capability. The shell was fabricated by dimethylmaleic acid modification of mPEG-PEI600 copolymer and exhibited tumor microenvironment-triggered charge reversal, leading to the shell detachment from the core at the tumor site. The nanoplatform with cascaded responsive property displays prolonged blood circulation time benefiting from PEGylated shielding once being injected into blood, subsequently effective accumulation at tumor tissues from blood induced by the elevated EPR effect resulting from the microenvironment-driven synchronous charge conversion and size shrinkage, and finally controlled gene release in tumor cell cytosol facilitated by glutathione-triggered HPAP degradability. In vitro and in vivo assays demonstrated that such a blood–tissue–cell cascaded responsive nanoplatform not only possessed imaging-trackable tumor-specific delivery ability but also exhibited enhanced and selective antitumor activity through TRAIL-mediated apoptosis as well as excellent biocompatibility. This study provides a multifunctional integration strategy, paving the way for designing novel theranostic nanomedicines on the basis of precision medicine.

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Thermosensitive poly(N-isopropylacrylamide) (PNIPAM), hydrophilic below its lower critical solution temperature (LCST) of 32 °C and hydrophobic above it, has been widely used as a drug and gene delivery system with intelligent temperature-responsivity.

It is well known that spirostane-type saponins show various bioactivities. In our on-going program of screening these kinds of constituents from natural products, Yucca schidigera was found to be rich in them, and nine new spirostanol saponins, Yucca spirostanosides A1 (1), A2 (2), B1 (3), B2 (4), B3 (5), C1 (6), C2 (7), C3 (8), and D1 (9), together with five known ones (10–14) were isolated from the plant. Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR and MS spectra, and comparing with published data.