Deciphering the Microdroplet Acceleration Factors of Aza-Michael Addition Reactions.

Microdroplet chemistry is emerging as a great tool for accelerating reactions by several orders of magnitude. Several unique properties such as extreme pHs, interfacial electric fields (IEFs), and partial solvation have been reported to be responsible for the acceleration; however, which factor plays the key role remains elusive. Here, we performed quantum chemical calculations to explore the underlying mechanisms of an aza-Michael addition reaction between methylamine and acrylamide. We showed that the acceleration in methanol microdroplets results from the cumulative effects of several factors. The acidic surface of the microdroplet plays a dominating role, leading to a decrease of ∼9 kcal/mol in the activation barrier. We speculated that the dissociation of both methanol and trace water contributes to the surface acidity. An IEF of 0.1 V/Šcan further decrease the barrier by ∼2 kcal/mol. Partial solvation has a negligible effect on lowering the activation barrier in microdroplets but can increase the collision frequency between reactants. With acidity revealed to be the major accelerating factor for methanol droplets, reactions on water microdroplets should have even higher rates because water is more acidic. Both theoretically and experimentally, we confirmed that water microdroplets significantly accelerate the aza-Michael reaction, achieving an acceleration factor that exceeds 107. This work elucidates the multifactorial influences on the microdroplet acceleration mechanism, and with such detailed mechanistic investigations, we anticipate that microdroplet chemistry will be an avenue rich in opportunities in the realm of green synthesis.

Paeoniflorin increases the anti-tumor efficacy of sorafenib in tumor-bearing mice with liver cancer via suppressing the NF-κb/PD-l1 axis.

Background: Sorafenib (Sor) represents a first-line therapy for hepatocellular carcinoma (HCC); however, its efficacy is constrained by secondary failure, which limits its clinical use. Recent studies have indicated that the suppression of Programmed cell death-Ligand 1 (PD-L1) may potentiate Sor's anti-liver cancer effects; furthermore, PD-L1 expression is known to be regulated by NF-κB. Previous research has demonstrated that paeoniflorin (PF) downregulates the NF-κB axis, nevertheless, current research has not yet determined whether PF can synergistically enhance the efficacy of Sor against HCC by modulating the NF-κB/PD-L1 pathway. Methods: The study employed a H22 hepatoma-bearing mouse model, which was treated with PF, Sor, and their combination over a period of 12 days. The impact of PF and Sor on tumor growth, proliferation, apoptosis, T-cell subsets, IL-2 and IFN-γ production, and NF-κB and PD-L1 expression was assessed. Moreover, Splenic lymphocyte from normal mice and tumor cells from model mice were co-cultured in vitro, and the tumor-specific cytotoxic T lymphocyte activity was analyzed. In the final phase of the study, Huh-7 cells were stimulated with PF in combination with an NF-κB activator or inhibitor, and the subsequent production of NF-κB and PD-L1 was investigated. Results: PF and Sor exhibit a synergistic anti-tumor effect, compared to the use of Sor alone, the combined use of PF and Sor significantly increased the number of CD4+ and CD8+ T cells in tumor tissue, markedly enhanced the cytotoxic activity of tumor-specific cytotoxic T lymphocytes, and reversed the depletion of interleukin-2 and the increase in PD-L1 expression following Sor intervention. This combination also further reduced the level of IFN-γ in peripheral blood and the expression of NF-κB and PD-L1 in tumor tissue. Additionally, in vitro experiments confirmed that PF reduces the expression of PD-L1 in Huh-7 liver cancer cells by inhibiting NF-κB. Conclusions: PF plays a synergistic role of Sor inhibiting HCC progression by regulating the NF-κB/PD-L1 pathway.

Real-Time and Online Monitoring of Hazardous Volatile Organic Compounds in Environmental Water by an Unmanned Shipborne Mass Spectrometer System.

Hazardous volatile organic compounds (VOCs) are one of the critical concerns in environmental water due to their toxicity to aquatic organisms and drinking water. Therefore, rapid detection of hazardous VOCs in environmental water is highly needed as many analytical methods are limited to on-site monitoring. In this work, we designed a novel unmanned shipborne mass spectrometer (US-MS) system for the real-time and online monitoring of hazardous VOCs in environmental water. The US-MS system consists of a miniaturized mass spectrometer, an automatic sampling device, a robust unmanned ship, and other monitoring and control devices. Along with the navigation route of the US-MS system, environmental water was continuously introduced into the MS system for the online and real-time detection of hazardous VOCs via a liquid/gas exchange membrane. Analytical performances of the US-MS system were investigated by a mixture of 10 VOCs showing low limits of detection (LODs: 0.31-1.26 ng/mL), good reproducibility (RSDs: 2.93-11.03%, n = 7), and excellent quantitative ability (R2 > 0.99). Furthermore, on-site detection and online monitoring of hazardous volatile contaminants such as benzene, chloroprene, and toluene in different aquatic environments such as rivers and lakes were successfully demonstrated, showing excellent field applicability of the US-MS system. Overall, the newly developed US-MS system could perform on-site, online, and real-time monitoring of complex VOCs in environmental water, showing good performances and versatile applications in water analysis.

High Electric Fields on Water Microdroplets Catalyze Spontaneous and Fast Reactions in Halogen-Bond Complexes.

The use of external electric fields as green and efficient catalysts in synthetic chemistry has recently received significant attention for their ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Technically, methods of generating high electric fields in the range of 1-10 V/nm are limited, as in-vacuo techniques have obvious scalability issues. The spontaneous high fields at various interfaces promise to solve this problem. In this study, we take advantage of the spontaneous high electric field at the air-water interface of sprayed water microdroplets in the reactions of several halogen bond systems: Nu:--X-X, where Nu: is pyridine or quinuclidine and X is bromine or iodine. The field facilitates ultrafast electron transfer from Nu:, yielding a Nu-X covalent bond and causing the X-X bond to cleave. This reaction occurs in microseconds in microdroplets but takes days to weeks in bulk solution. Density functional theory calculations predict that the reaction becomes barrier-free in the presence of oriented external electric fields, supporting the notion that the electric fields in the water droplets are responsible for the catalysis. We anticipate that microdroplet chemistry will be an avenue rich in opportunities in the reactions facilitated by high electric fields and provides an alternative way to tackle the scalability problem.

The Spontaneous Electron-Mediated Redox Processes on Sprayed Water Microdroplets.

Water is considered as an inert environment for the dispersion of many chemical systems. However, by simply spraying bulk water into microsized droplets, the water microdroplets have been shown to possess a large plethora of unique properties, including the ability to accelerate chemical reactions by several orders of magnitude compared to the same reactions in bulk water, and/or to trigger spontaneous reactions that cannot occur in bulk water. A high electric field (∼109 V/m) at the air-water interface of microdroplets has been postulated to be the probable cause of the unique chemistries. This high field can even oxidize electrons out of hydroxide ions or other closed-shell molecules dissolved in water, forming radicals and electrons. Subsequently, the electrons can trigger further reduction processes. In this Perspective, by showing a large number of such electron-mediated redox reactions, and by studying the kinetics of these reactions, we opine that the redox reactions on sprayed water microdroplets are essentially processes using electrons as the charge carriers. The potential impacts of the redox capability of microdroplets are also discussed in a larger context of synthetic chemistry and atmospheric chemistry.

Dual-Band Wide-Angle Reflective Circular Polarization Converter with Orthogonal Polarization Modes.

Herein a dual-band wide-angle reflective circular polarization converter, based on a metasurface was developed. The unit cell is composed of a split square ring and a nested square patch. The split square ring plays the role of creating polarization conversion. The square patch is useful for improving the quality of axial ratio. It was verified that the structure could transform the x-polarized incident wave into left-hand circular polarization in the lower frequency band, and to right-hand circular polarization in the higher frequency band. For y-polarized incidence, the transformation has orthogonal modes to that for x-polarized incidence. Moreover, the 3 dB axial ratio takes place in the ranges of 8.42-12.32 GHz and 18.74-29.73 GHz, corresponding to a relative bandwidth of 37.61%, and 45.35%, respectively. In addition, the polarization conversion efficiency is greater than 99% in the ranges of 8.65-11.83 GHz and 19.55-29.36 GHz. Furthermore, for oblique incidence, the axial ratio remains stable, even at 50° incidence, for the lower frequency band. Lastly, a prototype is fabricated and measured for experimental verification. The measured and simulated results were in good agreement. Compared with other designs in the literature, the proposed converter operates with good performance in dual-band, with high-efficiency, and with angular stability.

Roles of Fe-C amendment on sulfate-containing pharmaceutical wastewater anaerobic treatment: Microbial community and sulfur metabolism.

The effects of multiple two-phase anaerobic treatment involving acidification coupling Fe-C on sulfate-containing chemical synthesis-based pharmaceutical wastewater treatment were investigated. Fe-C was added as a filler with 25% vol. to acidogenic reactors for semi-continuous operation. The results suggested that Fe-C amendment promoted sulfate removal efficiency by 47.5% and shortened the reaction time by 50% in the acidogenic phase. With mitigation of sulfate inhibition, SCOD removal efficiency and methane production were further increased by 24.6% and 398% compared to direct raw wastewater anaerobic digestion, respectively, in methanogenic phase. The results of sulfate removal kinetics confirmed a 150% increase of removal rate in acidogenic phase. However, the apparent kinetic microbial sulfate removal constant without Fe-C amendment was maintained at approximately 0.06 h-1. The Fe-C amendment not only increased the relative abundance of Methanothrix and Desulfovibrio for sulfate reduction but also enriched unclassified_p__Chloroflexi and unclassified_c__Deltaproteobacteria for acidification. Metagenomic results indicated that Fe-C enhanced dissimilatory sulfate reduction and PAPS synthesis of assimilatory step. The hydrogen sulfide production through the 3-mercaptopyruvate to pyruvate pathways was also enhanced. Butyrate-oxidizing genes were increased synchronously to convert butyrate to acetate.

Magnetic Ionic Liquids as Solvents for RNA Extraction and Preservation.

Ribonucleic acid (RNA) is particularly sensitive to enzymatic degradation by endonucleases prior to sample analysis. In-field preservation has been a challenge for RNA sample preparation. Very recently, hydrophobic magnetic ionic liquids (MIL) have shown significant promise in the area of RNA extraction. In this study, MILs were synthesized and employed as solvents for the extraction and preservation of RNA in aqueous solution. RNA samples obtained from yeast cells were extracted and preserved by the trihexyl(tetradecyl) phosphonium tris(hexafluoroacetylaceto)cobaltate(II) ([P66614 +][Co(hfacac)3 -]) and trihexyl(tetradecyl) phosphonium tris(phenyltrifluoroacetylaceto)cobaltate(II) ([P66614 +][Co(Phtfacac)3 -]) MIL with a dispersion of the supporting media, polypropylene glycol, at room temperature for up to a 7 and 15 day period, respectively. High-quality RNA treated with ribonuclease A (RNase A) was recovered from the tetra(1-octylimidazole)cobaltate(II) di(l-glutamate) ([Co(OIM)4 2+][Glu-]2) and tetra(1-octylimidazole)cobaltate(II) di(l-aspartate) ([Co(OIM)4 2+][Asp-]2) MILs after a 24 h period at room temperature. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and agarose gel electrophoresis were used to determine the effect of RNA preservation. Furthermore, the preservation mechanism was investigated by exploring the partitioning of RNase A into the MIL using high-performance liquid chromatography.

Author Correction: Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Selective hybridization and capture of KRAS DNA from plasma and blood using ion-tagged oligonucleotide probes coupled to magnetic ionic liquids.

Detection of circulating tumor DNA (ctDNA) presents several challenges due to single-nucleotide polymorphisms and large amounts of background DNA. Previously, we reported a sequence-specific DNA extraction procedure utilizing functionalized oligonucleotides called ion-tagged oligonucleotides (ITOs) and disubstituted ion-tagged oligonucleotides (DTOs). ITOs and DTOs are capable of hybridizing to complementary DNA for subsequent capture by a magnetic ionic liquid (MIL) through hydrophobic interactions, π-π stacking, and fluorophilic interactions. However, the performance of the ITOs and DTOs in complex sample matrices has not yet been evaluated. In this study, we compare the amount of KRAS DNA extracted using ITO and DTOs from saline, 2-fold diluted plasma, 10-fold diluted plasma, and 10-fold diluted blood. We demonstrate that ITO/DTO-MIL extraction is capable of selectively preconcentrating DNA from diluted plasma and blood without additional sample preparation steps. In comparison, streptavidin-coated magnetic beads were unable to selectively extract DNA from 10-fold diluted plasma and 10-fold diluted blood without additional sample clean-up steps. Significantly more DNA could be extracted from 2-fold diluted plasma and 10-fold diluted blood matrices using the DTO probes compared to the ITO probes, likely due to stronger interactions between the probe and MIL. The ability of the DTO-MIL method to selectively preconcentrate small concentrations of DNA from complex biological matrices suggests that this method could be beneficial for ctDNA analysis.

Maximizing Ion-Tagged Oligonucleotide Loading on Magnetic Ionic Liquid Supports for the Sequence-Specific Extraction of Nucleic Acids.

Targeted nucleic acid analysis requires the highly selective extraction of desired DNA fragments in order to minimize interferences from samples with abundant heterogeneous sequences. We previously reported a method based on functionalized oligonucleotide probes known as ion-tagged oligonucleotides (ITOs) that hybridize with complementary DNA targets for subsequent capture using a hydrophobic magnetic ionic liquid (MIL) support. Although the ITO-MIL approach enriched specific DNA sequences in quantities comparable to a commercial magnetic bead-based method, the modest affinity of the ITO for the hydrophobic MIL limited the yield of DNA targets, particularly when stringent wash conditions were applied to remove untargeted DNA. Here, we report the synthesis and characterization of a series of ITOs in which functional groups were installed within the cation and anion components of the tag moiety in order to facilitate loading of the ITO to the MIL support phase. In addition to hydrophobic interactions, we demonstrate that π-π stacking and fluorophilic interactions can be exploited for loading oligonucleotide probes onto MILs. Using a disubstituted ion-tagged oligonucleotide (DTO) possessing two linear C8 groups, nearly quantitative loading of the probe onto the MIL support was achieved. The enhanced stability of the DTO within the MIL solvent permitted successive wash steps without the loss of the DNA target compared to a monosubstituted ITO with a single C8 group that was susceptible to increased loss of analyte. Furthermore, the successful capture of a 120 bp KRAS fragment from human plasma samples followed by real-time quantitative polymerase chain reaction (qPCR) amplification is demonstrated.

Coupling oligonucleotides possessing a poly-cytosine tag with magnetic ionic liquids for sequence-specific DNA analysis.

Oligonucleotide probes were designed with a poly-cytosine region that facilitates stable anchoring to a magnetic ionic liquid support. By tethering a recognition sequence to the poly-C tag, the resulting diblock oligonucleotides distinguished single-nucleotide variants and captured DNA targets from interfering genomic DNA and cell lysate for qPCR amplification.

An Optimization Routing Algorithm for Green Communication in Underground Mines.

With the long-term dependence of humans on ore-based energy, underground mines are utilized around the world, and underground mining is often dangerous. Therefore, many underground mines have established networks that manage and acquire information from sensor nodes deployed on miners and in other places. Since the power supplies of many mobile sensor nodes are batteries, green communication is an effective approach of reducing the energy consumption of a network and extending its longevity. To reduce the energy consumption of networks, all factors that negatively influence the lifetime should be considered. The degree constraint minimum spanning tree (DCMST) is introduced in this study to consider all the heterogeneous factors and assign weights for the next step of the evaluation. Then, a genetic algorithm (GA) is introduced to cluster sensor nodes in the network and balance energy consumption according to several heterogeneous factors and routing paths from DCMST. Based on a comparison of the simulation results, the optimization routing algorithm proposed in this study for use in green communication in underground mines can effectively reduce the network energy consumption and extend the lifetimes of networks.

Wet Cupping Therapy Improves Local Blood Perfusion and Analgesic Effects in Patients with Nerve-Root Type Cervical Spondylosis.

OBJECTIVE: To observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS). METHODS: Fifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment efficacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flowmetry, and its variations before and after treatment in both groups were compared as well. RESULTS: In both groups, the VAS scores significantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints significantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05). CONCLUSIONS: WCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

Targeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits anti-oxidative and anti-cancer activities at levels exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. Herein, we demonstrate that MSA inhibited angiogenesis at 2 µM, which falls in the range of moderate Se nutritional status. We found that MSA treatments at 2 µM increased cell adherence, while inhibiting cell migration and tube formation of HUVECs in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin ß3 at the levels of mRNA and protein, and disrupted clustering of integrin ß3 on the cell surface. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB. Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels not only by down-regulating the expression of integrin ß3 but also by disorganizing the clustering of integrin ß3, which further inhibited the phosphorylation involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy in clinical settings.

Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy.

In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.

Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation.

BACKGROUND: Selenium (Se) is an essential micronutrient trace element and an established nutritional antioxidant. Low Se status exacerbates inflammatory bowel diseases progression, which involves hyper inflammation in the digestive tract. Se nanoparticles (SeNPs) exhibit anti-inflammatory activity accompanied by low toxicity, especially when decorated with natural biological compounds. Herein, we explored the beneficial effects of SeNPs decorated with Ulva lactuca polysaccharide (ULP) in mice subjected to the acute colitis model. RESULTS: We constructed SeNPs coated with ULP (ULP-SeNPs) in average diameter ~130 nm and demonstrated their stability and homogeneity. Supplementation with ULP-SeNPs (0.8 ppm Se) resulted in a significant protective effect on DSS-induced acute colitis in mice including mitigation of body weight loss, and colonic inflammatory damage. ULP-SeNPs ameliorated macrophage infiltration as evidenced by decreased CD68 levels in colon tissue sections. The anti-inflammatory effects of ULP-SeNPs were found to involve modulation of cytokines including IL-6 and TNF-α. Mechanistically, ULP-SeNPs inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which drives the transcription of these pro-inflammatory cytokines. CONCLUSIONS: ULP-SeNPs supplementation may offer therapeutic potential for reducing the symptoms of acute colitis through its anti-inflammatory actions.

Multifunctional Mesoporous Silica Nanoparticles with Thermal-Responsive Gatekeeper for NIR Light-Triggered Chemo/Photothermal-Therapy.

In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host-guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.

Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD.

Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self-Synergistic Tumor Targeting Therapy.

In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self-synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase-rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell-penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on-demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor-made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self-synergistically therapeutic capacity opens new avenues for cancer therapy.