Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide-bond-containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual-responsiveness is reported. These diselenide-bridged MSNs can encapsulate cytotoxic RNase A into the 8-10 nm internal pores via electrostatic interaction and release the payload via a matrix-degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer-cell-derived membrane fragments, these bioinspired RNase A-loaded MSNs exhibit homologous targeting and immune-invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti-cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell-membrane-coated, dual-responsive degradable MSNs represent a promising platform for the delivery of bio-macromolecules such as protein and nucleic acid therapeutics.

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There is a pressing need to develop nanoplatforms that integrate multimodal therapeutics to improve treatment responses and prolong the survival of patients with unresectable hepatocellular carcinoma (HCC). Mesoporous silica-coated gold nanomaterials have emerged as a novel multifunctional platform combining tunable surface plasmon resonance and mesoporous properties that exhibit multimodality properties in cancer theranostics. However, their reduced radiation-absorption efficiency and limited surface area hinder their further radiochemotherapeutic applications. To address these issues, we designed Janus-structured gold-mesoporous silica nanoparticles using a modified sol-gel method. This multifunctional theranostic nanoplatform was subsequently modified via the conjugation of folic acid for enhanced HCC targeting and internalization. The loaded anticancer agent doxorubicin can be released from the mesopores in a pH-responsive manner, facilitating selective and safe chemotherapy. Additionally, the combination of chemotherapy and radiotherapy induced synergistic anticancer effects in vitro and exhibited remarkable inhibition of tumor growth in vivo along with significantly reduced systematic toxicity. Additionally, the Janus NPs acted as targeted computed tomography (CT)-imaging agents for HCC diagnosis. Given their better performance in chemoradiotherapy and CT imaging as compared with that of their core-shell counterparts, this new nanoplatform designed with dual functionalities provides a promising strategy for unresectable HCC theranostics.

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Mesenchymal stem cells (MSCs) hold great potential for tissue engineering and regeneration medicine. However, for clinical use, MSCs may be detrimental due to their uncertain fate during the transplantation. It is therefore highly desirable to develop biocompatible nanomaterials to integrate cell fate regulation with monitoring for MSC-based therapy. Herein, we employ recently developed citric acid-based carbon dots (CDs) and their derivatives (Et-IPCA) for labeling and tracking of rat bone marrow mesenchymal stem cells (rBMSCs). We further investigate their biocompatibility and effects on the osteogenic differentiation of rBMSCs. These highly fluorescent probes provide labeling of rBMSCs by internalization without affecting cell viability or inducing apoptosis when the concentration is lower than 50 μg mL. Importantly, the presence of the CDs and Et-IPCA facilitates high-efficiency osteogenic differentiation of rBMSCs by promoting osteogenic transcription and enhancing matrix mineralization. Compared to Et-IPCA, CDs considerably provide long-term tracking and promote the differentiation of rBMSCs toward osteoblasts through the ROS-mediated MAPK pathway. Taken together, our results consistently demonstrate that carbon dots are capable of both tracking and enhancing the osteogenic differentiation of MSCs. This study sheds new light on the potential of carbon dots as a bifunctional tool in the thriving field of MSC-based therapy.

Engineered nanoparticles have provided a basis for innovative agricultural applications, specifically in plant disease management. In this interdisciplinary study, by conducting comparison studies using macroscale magnesium oxide (mMgO), we evaluated the fungicidal activity of MgO nanoparticles (nMgO) against soilborne Phytophthora nicotianae and Thielaviopsis basicola for the first time under laboratory and greenhouse conditions. In vitro studies revealed that nMgO could inhibit fungal growth and spore germination and impede sporangium development more efficiently than could macroscale equivalents. Indispensably, direct contact interactions between nanoparticles and fungal cells or nanoparticle adsorption thereof were found, subsequently provoking cell morphological changes by scanning electron microscopy/energy-dispersive spectrometry (SEM/EDS) and transmission electron microscopy (TEM). In addition, the disturbance of the zeta potential and accumulation of various modes of oxidative stress in nMgO-exposed fungal cells accounted for the underlying antifungal mechanism. In the greenhouse, approximately 36.58 and 42.35% decreases in tobacco black shank and black root rot disease, respectively, could testify to the efficiency by which 500 µg/ml of nMgO suppressed fungal invasion through root irrigation (the final control efficiency reached 50.20 and 62.10%, respectively) when compared with that of untreated controls or mMgO. This study will extend our understanding of nanoparticles potentially being adopted as an effective strategy for preventing diversified fungal infections in agricultural fields.

Stimuli-triggered nanoplatforms have become attractive candidates for combined strategies for advanced liver cancer treatment. In this study, we designed a light-responsive nanoplatform with folic acid-targeting properties to surmount the poor aqueous stability and photostability of indocyanine green (ICG). In this Janus nanostructure, ICG was released on-demand from mesoporous silica compartments in response to near-infrared (NIR) irradiation, exhibiting predominant properties to convert light to heat in the cytoplasm to kill liver cancer cells. Importantly, the silver ions released from the silver compartment that were triggered by light could induce efficient chemotherapy to supplement photothermal therapy. Under NIR irradiation, ICG-loaded Janus nanoplatforms exhibited synergistic therapeutic capabilities both in vitro and in vivo compared with free ICG and ICG-loaded mesoporous silica nanoparticles themselves. Hence, our Janus nanoplatform could integrate ICG-based photothermal therapy and silver ion-based chemotherapy in a cascade manner, which might provide an efficient and safe strategy for combined liver cancer therapy.

The vesicular acetylcholine transporter (VAChT) is responsible for the transport of the neurotransmitter acetylcholine (ACh) into synaptic vesicles using an electrochemical gradient to drive transport. Rat VAChT has a number of aspartate residues within its predicted transmembrane domains (TM) and cytoplasmic loops, which may play important structural or functional roles in acetylcholine transport. In order to identify functional charged residues, site-directed mutagenesis of rVAChT was undertaken. No effect on ACh transport was observed when any of the five aspartate residues in the cytoplasmic loop were converted to asparagine. Similarly, changing Asp-46 (D46N) in TM1 or Asp-255 (D255N) in TM6 had no effect on ACh transport or vesamicol binding.