Toxic effects of nanoplastics on biological nitrogen removal in constructed wetlands: Evidence from iron utilization and metabolism.

Nanoplastics (NPs) in wastewaters may present a potential threat to biological nitrogen removal in constructed wetlands (CWs). Iron ions are pivotal in microbially mediated nitrogen metabolism, however, explicit evidence demonstrating the impact of NPs on nitrogen removal regulated by iron utilization and metabolism remains unclear. Here, we investigated how NPs disturb intracellular iron homeostasis, consequently interfering with the coupling mechanism between iron utilization and nitrogen metabolism in CWs. Results indicated that microorganisms affected by NPs developed a siderophore-mediated iron acquisition mechanism to compensate for iron loss. This deficiency resulted from NPs internalization limited the activity of the electron transport system and key enzymes involved in nitrogen metabolism. Microbial network analysis further suggested that NPs exposure could potentially trigger destabilization in microbial networks and impair effective microbial communication, and ultimately inhibit nitrogen metabolism. These adverse effects, accompanied by the dominance of Fe3+ over certain electron acceptors engaged in nitrogen metabolism under NPs exposure, were potentially responsible for the observed significant deterioration in nitrogen removal (decreased by 30 %). This study sheds light on the potential impact of NPs on intracellular iron utilization and offers a substantial understanding of the iron-nitrogen coupling mechanisms in CWs.

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.

A refined management system focusing on medication dispensing errors: A 14-year retrospective study of a hospital outpatient pharmacy.

Objectives: This study aimed to evaluate the efficiency of a 14-year refined management system for the reduction of dispensing errors in a large-scale hospital outpatient pharmacy and to determine the effects of person-related and environment-related factors on the occurrence of dispensing errors. Methods: A retrospective study was performed. Data on dispensing errors, inventory and account management from 2008 to 2021 were collected from the electronic system and evaluated using the direct observation method and the Plan-Do-Check-Act (PDCA) cycle. Results: The consistency of the inventory and accounts increased substantially (from 86.93 % to 99.75 %) with the implementation of the refined management program. From 2008 to 2021, the total number of dispensing errors was reduced by approximately 96.1 %. The number of dispensing errors in quantity and name was reduced by approximately 98.2 % and 95.07 %, respectively. A remarkable reduction in the error rate was achieved (from 0.014 % to 0.00002 %), and the rate of dispensing errors was significantly reduced (0.019 % vs. 0.0003 %, p < 0.001). Across all medication dispensing errors, human-related errors decreased substantially (208 vs. 7, p < 0.05), as did non-human-related errors also (202 vs. 9, p < 0.05). There was a correlation between the occurrence of errors and pharmacists' sex (females generally made fewer errors than males), age (more errors were made by those aged 31-40 years), and working years (more errors were made by those with more than 11 years of work experience) from 2016 to 2021. The technicians improved during this procedure. Conclusions: Refined management using the PDCA cycle was helpful in preventing dispensing errors and improving medication safety for patients.

Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy.

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.

Illuminating plant-microbe interaction: How photoperiod affects rhizosphere and pollutant removal in constructed wetland?

Rhizosphere is a crucial area in comprehending the interaction between plants and microorganisms in constructed wetlands (CWs). However, influence of photoperiod, a key factor that regulates photosynthesis and rhizosphere microbial activity, remains largely unknown. This study investigated the effect of photoperiod (9, 12, 15 h/day) on pollutant removal and underlying mechanisms. Results showed that 15-hour photoperiod treatment exhibited the highest removal efficiencies for COD (87.26%), TN (63.32%), and NO3--N (97.79%). This treatment enhanced photosynthetic pigmentation and root activity, which increased transport of oxygen and soluble organic carbon to rhizosphere, thus promoting microbial nitrification and denitrification. Microbial community analysis revealed a more stable co-occurrence network due to increased complexity and aggregation in the 15-hour photoperiod treatment. Phaselicystis was identified as a key connector, which was responsible for transferring necessary carbon sources, ATP, and electron donors that supported and optimized nitrogen metabolism in the CWs. Structural equation model analysis emphasized the importance of plant-microbe interactions in pollutant removal through increased substance, information, and energy exchange. These findings offer valuable insights for CWs design and operation in various latitudes and rural areas for small-scale decentralized systems.

Thiol-modified hyaluronic acid improves the physical stability of curcumin-zein nanoparticles by forming disulfide bonds with zein.

Zein-based nanoparticles have been developed in the food industry. However, their poor pH stability and unfavorable ionic strength stability remain a challenge even with the use of polysaccharides (such as hyaluronic acid) as stabilizers. To address this shortcoming, an improved strategy based on the disulfide bonds between thiol-modified hyaluronic acid (HASH) and zein was proposed. In this study, curcumin-zein nanoparticles (ZNs-HASH) were prepared with HASH as a stabilizer. The ZNs-HASH displayed similar particle sizes and spherical structures with ZNs and ZNs-HA (HA as a stabilizer). The Fourier transform infrared spectroscopy demonstrated the formation of disulfide bonds between zein and HASH. Among the three formulations tested, ZNs-HASH exhibited the highest pH and salt ion stability and the strongest antioxidant capacity. This study provided new insights for the improvement of physical stability of zein nanoparticles and the development of oral bioactive substances by chemical modification of natural polysaccharides.

Exploring the resilience of constructed wetlands to harmful algal blooms disturbances: A study on microbial response mechanisms.

Constructed wetlands (CWs) have emerged as a promising environmentally sustainable technique for wastewater treatment. However, the susceptibility of CWs to disturbances caused by harmful algal blooms (HABs) raises concerns. This study aimed to investigate the impact of HABs on the pollutants' removal performance of CWs and the response of rhizosphere microbial community. Results revealed that CWs possessed an adaptive capacity that enabled them to recover caused by HABs. The rhizosphere was found to stimulate the occurrence of Acinetobacter, which played a critical role to help resist HABs disturbance. This study also observed an increased dissimilatory nitrate reduction metabolic pathway which promoted denitrification and enhanced the nitrogen removal efficiency of CWs. Additionally, the structural equation model further suggested that dissolved oxygen exerted a significant influence on the microbial activities and then affected the pollutants removal performance. Overall, our findings shed light on the mechanism for CW stability maintenance during HABs disturbance.

PARP inhibitor-related haemorrhages: What does the real-world study say?

Background: PARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event. Methods: A pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS). Results: 725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib. Conclusion: Recognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.

Microalgae-based constructed wetland system enhances nitrogen removal and reduce carbon emissions: Performance and mechanisms.

Combination of constructed wetlands (CWs) and microalgae-based technologies has been proved as effective wastewater treatment option; however, little attention was paid to investigate the optimal combination ways. This study showed that the integrated system (IS) connecting microalgal pond with CWs exhibited improved pollutant-removal efficiencies and preferred carbon reduction effects compared to other alternatives such as coupled system or independent CWs. Microbial analysis demonstrated that core microorganisms (e.g., Acinetobacter and Thermomonas) of the IS were mostly associated with carbon, nitrogen, and energy metabolism. Based on co-occurrence networks, microbial quantity with denitrification function in the IS accounted for 71.01 % of the microorganism related to nitrogen metabolism, which was higher than that of 48.84 % in the independent CWs, indicating that the presence of microalgae in IS played important role in promoting biological denitrification. These findings provide insights into the microbial mechanism and highlights the complementary effects between microalgae and CWs.

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine.

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Surface Modification of Liposomes Using Folic Acid.

Liposomes are usually defined as spherically shaped microscopic vesicles that consist of one or more phospholipid bilayer membranes. They are widely used in drug delivery due to their biocompatibility, biodegradability, and stability. In recent years, a growing body of research shows that folic acid (FA)-modified liposomes can be targeted to deliver therapeutics to tumor and inflammation sites via receptor-mediated endocytosis between FA and folate receptor (FR). Taking this advantage, FA-modified liposomes are usually used in the targeted treatment of cancer, atherosclerosis, and arthrosis. In this chapter, we provided a classical thin-film hydration method to prepare FA-modified liposomes. We expect that our strategies would provide new opportunities for the development of FA-modified liposomes for research and clinical uses.

A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a serious and highly invasive epithelial malignancy that is closely associated with Epstein-Barr virus (EBV). Due to the lack of therapeutic vaccines for NPC, we selected EBV latent membrane protein 2 (LMP2) as a preferable targeting antigen to develop a lipid-based LMP2-mRNA (mLMP2) vaccine. Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into (2,3-dioleacyl propyl) trimethylammonium chloride (DOTAP)-based cationic liposomes to obtain the mRNA vaccine (LPX-mLMP2). The cell assays showed that the antigen-presenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2. LMP2 could subsequently be presented to form the peptide-major histocompatibility complex (pMHC). Furthermore, LPX-mLMP2 could accumulate in the spleen, express antigens, promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo. It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination. Additionally, the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer. Overall, we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC. We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy. Electronic Supplementary Material: Supplementary material (methods of cytotoxicity assay, LMP2 expression, hemolysis test, the results of purity and maturity of BMDCs, LMP2 expression, and evaluation of T cells in lymph nodes and gating strategy for CTLs) is available in the online version of this article at 10.1007/s12274-022-5254-x.

Vertical-scale spatial influence of radial oxygen loss on rhizosphere microbial community in constructed wetland.

Complex interactions between plants and microorganisms form the basis of constructed wetlands (CWs) for pollutant removal. In the rhizosphere, radial oxygen loss (ROL) plays a key role in the activity and abundance of functional microorganisms. However, little has been done to explore how ROL would influence the niche differentiation of microbial communities at different vertical spatial scales. We demonstrate that ROL decreases with depth, promoting an oxidation-reduction rhizosphere microecosystem in CWs. The high level of ROL in the upper layer could support the oxygen supply for aerobic bacteria (Haliangium), facilitating the COD (60%) and NH4+-N (50%) removal, whereas the enrichment of denitrifiers (e.g., Hydrogenophaga and Ralstonia) and methanotrophs (Methanobaterium) in the lower layer could stimulate denitrification. The function prediction results further certified that the abundance of genes catalyzing nitrifying and denitrification processes were significantly enhanced in the upper and bottom layers, respectively, which was attributed to the oxygen concentration gradient in the rhizosphere. This study contributes to further unraveling the rhizosphere effect and enables an improved understanding of the decontamination mechanisms of CWs.

The neglected potential source of microplastics from daily necessities: A study on protective mobile phone cases.

Microplastics (MPs) pollution has become a serious global environment problem. It is therefore of practical significance to investigate the MP pollution caused by using plastic materials on a daily basis. In this study, different protective mobile phone cases (PMPCs) were selected as a representative plastic commodity that are in contact with the human body for long periods to explore the generation and transportation of MPs during 3 months of actual use. The average abundances were 1122 particles cm-2 on the PMPC and 314 particles cm-2 on the palm, respectively. There were four main kinds of MPs produced during the use of different PMPCs, which indicated that waste plastics may be recycled and used as raw materials, resulting in a complex PMPC composition. The median sizes of MPs on the surfaces of PMPCs and palms were 28 and 32 µm, respectively, which were smaller than the sizes reported in other studies. The combined effect of ultraviolet ageing and friction was the main reason for MP generation during daily PMPC use. Based on the results of a fitted regression equation and Monte Carlo simulation, the sharply generation of MPs may occur when PMPC was used for approximately 33 days.

Successional dynamics of microbial communities in response to concentration perturbation in constructed wetland system.

Constructed wetlands (CWs) are widely considered as resilient systems able to adapt to environmental perturbations. Little attention has been paid, however, to microbial dynamics when CWs withstand and recover from external shock. To understand the resilience of CWs, this study investigated rhizosphere microbial dynamics when CWs were subjected to influent COD perturbation (200 mg/L-1600 mg/L). Results demonstrated that CWs had strong adaptability to different influent perturbations, characterized by transitions from fluctuating to stable pollutant removal. Microbial analysis showed that rhizosphere microorganisms competed for niches in response to increased COD concentrations, and Trichococcus played key roles in resisting concentration perturbations. Structural equation modeling indicated that rhizosphere community succession and microbial energy metabolism were shaped by pH and DO. These findings provide insights into the mechanism for CW stability maintenance when facing concentration perturbations.

Size distribution and inhalation exposure of airborne particle-bound polybrominated diphenyl ethers, new brominated flame retardants, organophosphate esters, and chlorinated paraffins at urban open consumption place.

At present, the global urban population has exceeded half of the total population and is still on the rise. Urban air pollution has attracted much attention, but most of the research focuses on typical pollution sources and indoor environment. This study reports the occurrence characteristics of particle-bound polybrominated diphenyl ethers (PBDEs), new brominated flame retardants (NBFRs), organophosphate esters (OPEs), short-chain chlorinated paraffins (SCCPs), and medium-chain chlorinated paraffins (MCCPs) at urban open consumption place. Among those pollutants detected in this study, the level of CPs was generally higher than other urban outdoor environments, and even higher than few indoor environments, such as house in Guangzhou (China) and Stockholm (Sweden). The size distributions of PBDEs and NBFRs exhibited bimodal peaks and that of SCCPs presented a unimodal peak, whereas no obvious trend was observed for OPEs or MCCPs. Additionally, the results of calculating the deposition fluxes of target pollutants in various regions based on the size distribution confirmed that total deposition was dominated by deposition in the head airways and alveolar region, and inhalation exposure in the current environment poses no significant health risk. Both discrepancy of the spatial distribution and principal component analysis indicated that sources of these organic pollutants may be related to the type of stores. Various construction and decoration materials might have been responsible for the high concentrations of OPEs and CPs, and thus, these materials require further analysis.

Effectiveness of idebenone nanorod formulations in the treatment of Alzheimer's disease.

Idebenone (IDB) has demonstrated the potential to treat mitochondrial and neurodegenerative diseases, including Alzheimer's disease (AD). However, its therapeutic effects are compromised by poor compliance due to low bioavailability. The objective of this study is to fabricate IDB nanorods (IDBNRs) to improve oral bioavailability and increase concentrations in the brain in order to enhance therapeutic effects of IDB in the treatment of AD. IDBNRs showed desired sizes and rod-shaped morphologies. The release rate and the antioxidant activity of IDBNRs were improved relative to other delivery routes. The plasma and brain concentrations were enhanced due to rapid release into the systemic circulation. In behavioral tests, mice treated orally with IDBNRs showed amelioration of AD-induced impairment of learning and memory. Thus, because of improved efficiency of drug delivery, doses can be reduced, and the compliance and therapeutic experience of patients can be improved. IDBNRs may provide effective and convenient treatments for AD patients in the future.

Interferon Regulatory Factor 5 siRNA-Loaded Folate-Modified Cationic Liposomes for Acute Lung Injury Therapy.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an overwhelming pulmonary inflammation with limited clinical treatment strategies. Interferon regulatory factor 5 (IRF5) is a crucial regulator of inflammation factors, which can be upregulated under an inflammatory state and related to the efferocytosis of macrophages. Herein, IRF5 was knockdown by small interfering RNA (siIRF5) to promote the anti-inflammatory effect of macrophages. Macrophage-targeting cationic liposome modified by folate (FA-LP) was developed to deliver siIRF5 (FA-LP/siIRF5). Liposomes were characterized for their particle size, zeta potential, protein adsorption and hemolysis of red blood cells. The amount of IRF5 mRNA and the expression of IRF5 were measured using quantitative reverse transcription PCR (RT-qPCR) and western blot, respectively. The phenotype and efferocytosis of macrophages and the regulatory pathway of efferocytosis and biodistribution of liposomes in the ALI mice model were investigated. Data revealed that FA-LP/siIRF5 could obviously downregulate the expression of IRF5 in macrophages, skewing the polarization of macrophages to M2 phenotype (anti-inflammatory state) and thus improving their efferocytosis. Moreover, regulation of efferocytosis of macrophages by siIRF5 is related to the NF- B pathway. The in vivo biodistribution of FA-LP exhibited higher accumulation in the inflammatory lungs, suggesting that FA-LP could be considered as a promising gene delivery system and FA-LP/siIRF5 is an alternative strategy for the treatment of ALI/ARDS. To the best of our knowledge, this is the first study reporting that siIRF5 can be used for the treatment of ALI/ARDS.

Insights into Persistent Toxic Substances in Protective Cases of Mobile Phones: Occurrence, Health Risks, and Implications.

Despite the popularity of smartphones worldwide, persistent toxic substances (PTSs) in protective cases of mobile phones (PCMPs) and their health risks via direct skin contact have been ignored. This study investigated PTSs in PCMPs made in China with different materials and sales territory and their potential harm to human health. Polybrominated diphenyl ethers (PBDEs, 6.40 ng/g), new brominated flame retardants (NBFRs, 144 ng/g), organophosphate esters (OPEs, 10.1 µg/g), short-chain chlorinated paraffins (SCCPs, 3.58 µg/g), medium-chain chlorinated paraffins (MCCPs, 3.17 µg/g), and heavy metals (HMs, 72.3 µg/g) were detected. It was found that the different concentrations and compositions depend on the material, region, and use. Moreover, the raw materials used to fabricate PCMPs are of variable quality and may include recycled plastic waste. There are no standard quality specifications for PCMPs, and different materials have different properties, including specific surface area and adsorption ability. The risk assessment performed by Monte Carlo simulations indicated that the PTSs evaluated pose no health risks to the general population and may have adverse effects on individual high-exposure populations. According to the results of this work, it is suggested that more stringent global specifications for the selection of raw materials should be established, including the content and structural characteristics of PTSs, limitations on the use of additives in the production process, and the handling after use.

Probing the Superiority of Diselenium Bond on Docetaxel Dimeric Prodrug Nanoassemblies: Small Roles Taking Big Responsibilities.

The current state of chemotherapy is far from satisfaction, restricted by the inefficient drug delivery and the off-target toxicity. Prodrug nanoassemblies are emerging as efficient platforms for chemotherapy. Herein, three docetaxel dimeric prodrugs are designed using diselenide bond, disulfide bond, or dicarbide bond as linkages. Interestingly, diselenide bond-bridged dimeric prodrug can self-assemble into stable nanoparticles with impressive high drug loading (≈70%, w/w). Compared with disulfide bond and dicarbide bond, diselenide bond greatly facilitates the self-assembly of dimeric prodrug, and then improves the colloidal stability, blood circulation time, and antitumor efficacy of prodrug nanoassemblies. Furthermore, the redox-sensitive diselenide bond can specifically respond to the overexpressed reactive oxygen species and glutathione in tumor cells, leading to tumor-specific drug release. Therefore, diselenide bond bridged prodrug nanoassemblies exhibit discriminating cytotoxicity between tumor cells and normal cells, significantly alleviating the systemic toxicity of docetaxel. The present work gains in-depth insight into the impact of diselenide bond on the dimeric prodrug nanoassemblies, and provides promising strategies for the rational design of the high efficiency-low toxicity chemotherapeutical nanomedicines.