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Recently, molybdenum sulfide (MoS

Rui Wang,1,* Yijing Yao,1,2,* Yihui Gao,1 Mengyao Liu,1 Qian Yu,3 Xuejiao Song,4 Xiao Han,5 Dechao Niu,6 Lixin Jiang1,2 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute of Ultrasound in Medicine, Shanghai, 200233, People’s Republic of China; 3Department of Ultrasonography, Shanghai Jiao Tong University Affiliated No. 6 Hospital, Shanghai, 200233, People’s Republic of China; 4School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, People’s Republic of China; 5Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 6Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lixin Jiang; Dechao Niu, Email jinger_28@sina.com; dcniu@ecust.edu.cnBackground: Pancreatic cancer is regarded as one of the most lethal types of tumor in the world, and optional way to treat the tumor are urgently needed. Cancer stem cells (CSCs) play a key role in the occurrence and development of pancreatic tumors. CD133 is a specific antigen for targeting the pancreatic CSCs subpopulation. Previous studies have shown that CSC-targeted therapy is effective in inhibiting tumorigenesis and transmission. However, CD133 targeted therapy combined with HIFU for pancreatic cancer is absent.Purpose: To improve therapeutic efficiency and minimize side effects, we carry a potent combination of CSCs antibody with synergist by an effective and visualized delivery nanocarrier to pancreatic cancer.Materials and Methods: Multifunctional CD133-targeted nanovesicles (CD133-grafted Cy5.5/PFOB@P-HVs) with encapsulated perfluorooctyl bromide (PFOB) in a 3-mercaptopropyltrimethoxysilane (MPTMS) shell modified with poly ethylene glycol (PEG) and superficially modified with CD133 and Cy 5.5 were constructed following the prescribed order. The nanovesicles were characterized for the biological and chemical characteristics feature. We explored the specific targeting capacity in vitro and the therapeutic effect in vivo.Results: The in vitro targeting experiment and in vivo FL and ultrasonic experiments showed the aggregation of CD133-grafted Cy5.5/PFOB@P-HVs around CSCs. In vivo FL imaging experiments demonstrated that the nanovesicles assemble for the highest concentration in the tumor at 24 h after administration. Under HIFU irradiation, the synergistic efficacy of the combination of the CD133-targeting carrier and HIFU for tumor treatment was obvious.Conclusion: CD133-grafted Cy5.5/PFOB@P-HVs combined with HIFU irradiation could enhance the tumor treatment effect not only by improving the delivery of nanovesicles but also by enhancing the HIFU thermal and mechanical effects in the tumor microenvironment, which is a highly effective targeted therapy for treating pancreatic cancer.Keywords: multifunctional nanovesicles, cancer stem cells, high-intensity focused ultrasound, in vivo fluorescent imaging, ultrasonic imaging

Nano-catalytic bacterial killing provides new opportunities to address ever-increasing antibiotic resistance. However, the intrinsic catalytic activity usually depends on a much lower pH condition (pH = 2 ∼ 5) than that in the weakly acidic bacterial microenvironment (pH = 6 ∼ 7) for reactive oxygen species production by Fenton reactions. Herein, a MnSiO

Although various drug nanocarriers have been developed for treating solid tumors, their clinical transformation is greatly limited by the difficulties in quantity production and unpredictable in vivo toxic effects. Herein, a facile "confined-gelation" strategy is developed to quantity-produce intelligent pluronic organosilica micelles (designated as IPOMs) with an undetectable critical micelle concentration (CMC), which features the self-assembly induced core confinement by block copolymers, the inner hydrolysis-condensation of silane to the oligomer skeleton, and oxidative cross-linking of disulfide skeleton to core gelation. The docetaxel-loaded IPOMs (DTX@IPOMs) with precise glutathione (GSH) responsiveness not only display an ultrahigh tolerated dose (360 mg/kg) in healthy Kunming mice model but also exhibit a remarkable tumor inhibition efficacy in both subcutaneous and orthotopic mice tumor models upon an extraordinarily large dosage (50 mg/kg). The present confined-gelation strategy provides a novel pathway to design and quantity-produce low-toxic and high-efficacy organic-inorganic hybrid nanodrugs in future clinical transformations.

Molybdenum oxide nanoparticles (NPs) with tunable plasmonic resonance in the near-infrared region display superior semiconducting features and photothermal properties, which are highly related to the crystalline and defective structures such as oxygen deficiencies. However, fundamental understanding on the structure-function relationship between crystalline/defective structures and photothermal properties is still unclear. To address this, herein, we have developed an “in-situ confined oxidation-reduction” strategy to regulate the defect features of molybdenum oxide NPs in the dual-mesoporous silica nanoreactor. Especially, the effects of crystalline structure/oxygen defects of molybdenum oxides on the photothermal performances were investigated by facilely tuning the amount of molybdenum resource and the reduction temperature. As a photothermal nanoagent, the optimal defective molybdenum oxide NPs encapsulated in PEGylated porous silica nanoreactor (designated as MoO3−x@PPSNs) exhibit excellent biological stability and strong localized surface plasmon resonance effect in near-infrared absorption range with the highest photothermal conversion efficiency up to 78.7% under 808 nm laser irradiation. More importantly, the remarkable photothermal effects of MoO3−xPPSNs were comprehensively demonstrated both in vitro and in vivo. Consequently, we envision that the plasmonic MoO3−x NPs in a biocompatible porous silica nano-reactor could be used as an efficient photothermal therapy agent for photothermal ablation of tumors.

The low sulfur utilization and fast capacity fading resulting from the sluggish redox reaction and abominable polysulfides shuttle greatly hinder the practical applications of lithium-sulfur (Li-S) batteries. Herein, we develop a facile “in-situ growth” method to decorate ultra-small Mo2C nanoparticles (US-Mo2C) on the surface of Ketjen Black (KB) to functionalize the commercial polypropylene (PP) separators, which can accelerate the redox kinetics of lithium polysulfides conversion and effectively increase the utilization of sulfur for Li-S batteries. Importantly, the US-Mo2C nanoparticles have abundant sites for chemical adsorption towards polysulfides and the conductive carbon networks of KB have cross-linked pore channels, which can promote electron transport and provide physical barrier and volume expansion space for polysulfides. Due to the combined effects of the US-Mo2C and KB, Li-S cells employing the multifunctional PP separators modified with KB/US-Mo2C composite (KB/US-Mo2C@PP) exhibit a high specific capacity (1212.8 mAh g−1 at 0.2 C), and maintain a reversible capacity of 1053.3 mAh g−1 after 100 cycles. More importantly, the KB/US-Mo2C@PP cells with higher sulfur mass loading of 4.9 mg cm−2 have superb areal capacity of 2.3 mAh cm−2. This work offers a novel and promising perspective for high-performance Li-S batteries from both the shuttle effect and the complex polysulfides conversion.

Unpredictable in vivo therapeutic feedback of hydroxyl radical (•OH) efficiency is the major bottleneck of chemodynamic therapy. Herein, we describe novel Fenton-based nanotheranostics NQ-Cy@Fe&GOD for spatio-temporally reporting intratumor •OH-mediated treatment, which innovatively unites dual-channel near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) signals. Specifically, MRI signal traces the dose distribution of Fenton-based iron oxide nanoparticles (IONPs) with high-spatial resolution, meanwhile timely fluorescence signal quantifies •OH-mediated therapeutic response with high spatio-temporal resolution. NQ-Cy@Fe&GOD can successfully monitor the intracellular release of IONPs and •OH-induced NQO1 enzyme in living cells and tumor-bearing mice, which makes a breakthrough in conquering the inherent unpredictable obstacles on spatio-temporally reporting chemodynamic therapy, so as to manipulate dose-dependent therapeutic process. This unprecedented strategy can elaborately bridge MRI and fluorescence imaging modality with spatio-temporal resolution, and paves a new pathway for accurately evaluating in situ generation of •OH feedback on the intratumoral catalytic Fenton reaction.

Upconversion nanoparticles (UCNPs) can convert near-infrared light (NIR, 980 or 808 nm) to ultraviolet (UV) or visible light, which can be widely used to improve tissue penetration depth in photodynamic therapy (PDT). Herein, we develop a kind of UCNP-based organosilica-micellar hybrid nanoplatform for redox-responsive chemotherapy and NIR-mediated PDT. The nanoplatform was constructed by the self-assembly of block copolymers polystyrene

An ideal drug delivery system is required to have high stability to ensure effective circulation and passive aggregation, good retention performance, and dynamic delivery and treatment monitoring. Thus, developing a kind of smart drug delivery carrier with both precise drug release and real-time detection is still a great challenge. Herein, we propose a confined crosslink protocol to prepare the intelligent hybrid delivery system for auto-fluorescent monitoring, protonation-induced retention, and precise drug release. The construction of this system involves the hydrolysis and condensation of (3-aminopropyl) triethoxysilane (APTES) silanes inside the Pluronic polymer micelles and thereafter a confined Schiff base crosslinking between glutaraldehyde (GA) and residual silane amino groups. The sizes of the intelligent docetaxel (DTX) nanosystem (designated as DFPN) change from ~25 nm in blood circulation or normal tissues (pH~7.4), to ~ 250 nm in slightly acidic environments (pH~6.5-7.0) due to the intra-molecular hydrogen bond-induced aggregation, and imine cleavage-induced disintegration in the endosome (pH~5.0-6.2) along with the auto-fluorescent monitoring contributing to the high-efficient chemotherapy. This work provides a new method to construct smart, acid-responsive, and fluorescent-guided drug delivery carrier systems for efficient and safe tumor chemotherapy.

Starvation-dependent differential stress sensitization effect between normal and tumor cells provides a potentially promising strategy to amplify chemotherapy effects and reduce side effects. However, the conventional starvation approaches such as glucose oxidase (Gox)-induced glucose depletion and nanomedicine-enabled vascular embolism usually suffer from aggravated tumor hypoxia, systemic toxicity, and unpredictable metabolic syndrome. Herein, a novel "valve-closing" starvation strategy is developed to amplify the chemotherapy effects via closing the "valve" of glucose transported into tumor cells, which is accomplished by a glucose transporters 1 (GLUT1, valve of glucose uptake) inhibitor (Genistein, Gen) and chemotherapeutic agent (Curcumin, Cur) coloaded hybrid organosilica-micelles nanomedicine (designated as (Gen + Cur)@FOS) with controllable stability. In vitro and in vivo results demonstrate that (Gen + Cur)@FOS can effectively reduce glucose/adenosine triphosphate levels in tumor cells by inhibiting GLUT1 expression (i.e., "valve-closing") to induce the starvation of tumor cells, thus weakening the resistance of tumor cells to apoptosis caused by chemotherapy, and consequently contributing to the remarkably improved antitumor efficiency and minimized side effects based on the stress sensitization effect mediated by GLUT1 inhibition-induced starvation. This "valve-closing" starvation strategy provides a promising paradigm for the development of novel nanotherapeutics with amplified chemotherapy effect.

Although various drug nanocarriers have been developed for treating solid tumors, their clinical transformation is greatly limited by the difficulties in quantity production and unpredictable

Simultaneous detection of multiple targets is in imperative demand but is challenging for analysis technology. In this study, a novel, multi-input luminescent logic system based on a nanoscale Zr(IV)/Eu(III) metal–organic framework (Zr-pydc-Eu) is designed for simultaneous identification and quantification of copper ions and hydrogen sulfide, which are considered to be not only toxic species in the environment but also associated with various physiological and pathological processes in the human body. In the MOF-based logic gate, pyridine-2,5-dicarboxylic acid (pydc) behaves as both the energy donor and the metal-chelating site, the photoactive Eu3+ ions function as the luminescence signal reporter/output, and the target analytes (Cu2+ and H2S) serve as energy modulators/inputs. By using the specific Cu2+ ions as a single input among various metal ions, the NOT logic operation is realized in Zr-pydc-Eu with the output switching from “1” to “0”. With the sequentially restored output from “0” to “1” by H2S input over the biologically relevant species, the IMPLICATION logic gate is implemented. Such features enable this Zr-pydc-Eu logic system to be an effective and smart platform for analyzing both Cu2+ and H2S with a low detection limit (10−8 M) and a real-time response (

Carbonaceous materials are extensively used as sodium-ion battery (SIB) anodes for their cost-effectiveness, high conductivity and reasonably high capacity. Unfortunately, these anodes suffer from poor rate performances and unsatisfactory lifespan. Herein, the design and construction of high nitrogen-doped, core–shell and intra-core mesoporous structured carbon nanospheres (designated as HN-CSMCNs) for high-rate and stable SIBs is reported. HN-CSMCNs are facilely synthesized by the self-assembly of block copolymer polystyrene-b-poly(acrylic acid), cetyltrimethylammonium bromide and dopamine hydrochloride, and subsequent pyrolysis under an NH3 atmosphere. As an anode for SIBs, HN-CSMCNs exhibit outstanding specific capacity (ca. 251 mA h g−1 at 0.1 A g−1), rate capability (ca. 104 mA h g−1 at 15 A g−1), and more importantly, especially stable cycling properties with a capacity of ca. 153 mA h g−1 being retained after 20 000 cycles at 10 A g−1. Electrochemical analysis demonstrates that the core–shell and intra-core mesoporous structures, expanded inter-planar distance and high pyrrolic/pyridinic-N doping of HN-CSMCNs together contribute to the superior sodium storage capability via a pseudocapacitive-dominated electrochemical kinetics, thus leading to superior electrochemical performances for SIBs.

Yolk-shell-structured nanoparticles (YSNs) provide useful carriers for applications in biomedicine and catalysis due to the excellent loading capability and versatile functionality of the flexible core and porous shell. Unfortunately, the reported YSNs always require complex multistep synthesis processes and a harsh hard-template etching strategy. Herein, a facile "selective extraction" strategy is developed to synthesize yolk-shell-structured polymer@void@mSiO

Recently, nanoparticle-triggered in situ catalytic Fenton/Fenton-like reaction is widely explored for tumor-specific chemodynamic therapy (CDT). However, despite the great potential of CDT in tumor treatment, insensitive response to the relatively high pH of the tumor sites and the insufficient intratumoral H

Limei Qin,1 Dechao Niu,1 Yu Jiang,1 Jianping He,1 Xiaobo Jia,1 Wenru Zhao,1 Pei Li,2 Yongsheng Li1 1Laboratory of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China; 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China Introduction: In this work, we have developed a novel “confined-growth” strategy to synthesize PEGylated multiple gold nanorices-encapsulated dual-mesoporous silica nanospheres (designated as PEGylated MGNRs@DMSSs) containing both small mesopores (2.5 nm) in the shell and large mesopores (21.7 nm) in the core based on a well-established, seed-mediated growth method. The photothermal effect and CT imaging ability were also studied.Methods: The nanoparticles were characterized by Fourier transform infrared (FT-IR) spectra, N2 absorption isotherms, Field-emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Confocal microscopy.Results: The longitudinally-localized surface (LSPR) absorption properties of MGNRs@DMSSs can be easily tuned by altering the amount of HAuCl4 in the gold growth solution. Additionally, the resultant PEGylated MGNRs@DMSSs have monodispersed, spherical morphology and good colloidal stability in an aqueous solution. More importantly, when exposed to NIR irradiation, the PEGylated MGNRs@DMSSs exhibit both higher temperature increments and better photothermal effects than that of single PEGylated gold nanorods at nearly an equivalent LSPR absorption. In addition, as CT contrast agents, the PEGylated MGNRs@DMSSs display a better CT imaging performance, in comparison with single PEGylated gold nanorods at the same Au concentration. Conclusion: Taken together, results indicate the potential for MGNRs@DMSSs used in CT imaging-guided photothermal therapy. Such a simple “confined-growth” strategy within a porous matrix offers a promising platform to design and prepare novel metal(s) oxide@silica nanocomposites for use in further cancer bio-imaging and therapy. Keywords: gold nanorices, dual-mesoporous silica, confined growth, imaging, photothermal effect &nbsp

Recently, Fe3O4-based materials have been widely studied as anodes in lithium-ion batteries (LIBs) because of the large theoretical capacity (924 mAh g–1) and environmental benignity. Unfortunately...

Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.

Natural antibodies are used widely for various applications such as in biomedical analysis, protein separation, and targeted-drug delivery, but they suffer from high cost and low stability. In this study, we developed a facile approach for the construction of antibody-like binding sites in a porous silica solid for efficient separation of bovine serum albumin (BSA) based on large-pore silica particles (LPSPs). This was accomplished by grafting two types of organosilane monomers, 3-aminopropyltriethoxylsilane (APTES) and octyltrimethoxysilane (OTMS), to provide hydrogen bonds or hydrophobic interactions with BSA through molecular imprinting technology. The resulting molecularly imprinted, large-pore silica particles (MI-LPSPs) were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TG), X-ray diffraction (XRD) and N2 sorption analysis. Results showed that the as-synthesized MI-LPSPs exhibited a spherical morphology, favorable stability and large pore structure. The kinetic adsorption experiments showed that the MI-LPSPs could reach equilibrium within one hour and were described well by the pseudo second-order model, indicating that chemical adsorption might be the rate-limiting step. Meanwhile, the MI-LPSPs had a large binding capacity up to 162.82 mg g−1 and high selectivity for the recognition of BSA. Moreover, such a high binding capacity and selectivity was retained after six runs, indicating a good stability and reusability of MI-LPSPs. Thus, it is expected that a simple synthetic methodology in the present study provides a promising pathway to prepare novel imprinted materials for efficient purification and separation of target proteins.

Gold-based nanocomposites have attracted intensive attention due to their unique optical properties and great potential in biomedical applications. Herein, we report a simple route for the synthesis of multiple gold nanorods encapsulated, hierarchically porous silica nanospheres (MGNRs@HPSNs) based on the cooperative self-assembly of amphiphilic block copolymer polystyrene-b-poly (acrylic acid) (PS-b-PAA), cetyl trimethyl ammonium bromide (CTAB), gold nanorods and the organosilane of tetraethyl orthosilicate (TEOS) in an oil/water system. Multiple gold nanorods have been loaded successfully into the interior of the hierarchically porous silica nanospheres, which consist of large, interconnected pores of 13.2 nm throughout the whole sphere and small pores of 2.7 nm in the silica framework. Moreover, the loading amount (or number) of gold nanorods in the silica matrix can be tuned by simply changing the initial concentration of preformed gold nanorods. Due to the presence of the hierarchically porous structure, the PEGylated MGNRs@HPSNs display high loading capability for both small anti-tumor drugs (i.e., doxorubicin hydrochloride, 69.2 ± 7.2 mg g−1) and bio-macromolecules (i.e., bovine serum albumin, 248.1 ± 12.3 mg g−1). More importantly, MGNRs@HPSNs present better photothermal effect than that of hierarchically porous silica nanoparticles containing less (one or two) gold nanorods at the same Au concentration. It is thus demonstrated that MGNRs@HPSNs can not only act as promising drug/protein nanocarriers, but also can be used as photoabsorbers for photothermal tumor therapy under NIR laser irradiation.

We present a simple route to fabricate peptide modified spherical gold nanoparticles (AuNPs@Pep1/Pep2) with enhanced retention performance in tumor sites for improved photothermal treatment (PTT), which was achieved through its in vivo self-assembly triggered by matrix metalloproteinase-2 (MMP-2).

Magnetic vesicles have attracted great attention due to their excellent magnetic properties and wide potentials for application in magnetic resonance imaging. In the present study, we designed and synthesized a new kind of supramolecular-based PEGylated magnetic hybrid vesicles (SPMHVs) that works as a T2-weighted MR contrast agent with ultra-high transverse relaxivity up to 641.7 mM−1 s−1. The construction of SPMHVs was achieved by self-assembly of the newly synthesized supramolecular-based amphiphilic pseudo-block copolymer polyrotaxane-poly (acrylic acid; PR-PAA) and hydrophobic magnetite nanoparticles, followed by cross-linking with organosilica of 3-mercaptopropyltrimethoxysilane (MPTMS) and poly (ethylene glycol; PEG) modification. Interestingly, the morphology of SPMHVs can be tuned between vesicles and micelles by changing the initial Fe3O4 concentrations in the oil phase (or the Fe3O4 loading amount). A sample of SPMHVs-30 nanoparticles obtained with initial magnetite concentration of 3.0 mg/ml in the oil phase especially displayed well-defined vesicular morphology, relatively small particle sizes (

In this work, a facile “soft-template” route to synthesize nitrogen-doped double-shelled hollow mesoporous carbon spheres (N-DHMCSs) has been developed by using anionic block copolymer polystyrene-b-poly(acrylic acid) (PS-b-PAA) micelles as soft template, tetraethyl orthosilicate (TEOS) as silica source, and dopamine (DA) as carbon and nitrogen sources, respectively. After carbonization of the PDA precursors and the removal of silica, the obtained N-DHMCSs present high specific surface area (>600 m2/g), adjustable nitrogen doping content (4.02%–5.91% in weight ratios), and unique double-shell hollow structures. Especially, the sample of N-DHMCSs-800 carbonized at 800 °C exhibits a high discharge specific capacity of 920.3 mA h/g at a current density of 0.1 A/g after 100 cycles. In addition, at a relative high current density of 0.5 A/g, its discharge specific capacity is up to 614.1 mA h/g even after 300 cycles. More importantly, it demonstrates excellent rate capabilities by the fact that a high reversib...

In this work, a novel kind of magnetic, core-shell structured and surface molecularly imprinted polymers (MMIPs) for the recognition of salicylic acid (SA) was facilely synthesized through a surface imprinting and sol-gel polymerization approach. The as-synthesized MMIPs exhibit uniform core-shell structure and favorable magnetic properties with a saturation magnetization of 22.8 emu g−1. The binding experiments demonstrated that MMIPs possessed high binding and specific recognition capacity, as well as fast binding kinetics and phase separation rate. The maximum binding capacity of MMIPs is around 36.8 mg g−1, nearly 6 times that of the magnetic non-imprinted polymers (MNIPs). Moreover, the selectivity experiments show that all the relative selectivity coefficients towards SA over its structure analogs are higher than 18, further indicating the markedly enhanced binding selectivity of MMIPs. Furthermore, the MMIPs were successfully applied for the determination of SA in environmental water samples with the recovery rates ranging from 94.0 to 108.0 %. This strategy may provide a versatile approach for the fabrication of well-defined molecularly imprinted polymers on nanomaterials for the analysis of complicated matrixes.

Oxidative stress is considered an efficient therapeutic target in the progression of osteoarthritis (OA). Unfortunately, the current drug delivery system for the reactive oxidative species (ROS) scavengers is still unsatisfactory due to their insufficient responsiveness and rapid joint clearance. In this study, we design and develop a smart anti-oxidative agent by constructing a dual-responsive hybrid micelle with free radical scavenger melanin in the micellar core and polydopamine on the shell (designated as DHMP/M) for photoacoustic imaging-guided knee OA therapy. The resulting DHMP/M displays a unique long-term controlled-release behavior involving the slow and persistent release under endogenous ROS stimuli and short-burst release capability triggered by exogenous near-infrared (NIR) light. More importantly, DHMP/M possesses excellent free radical scavenging capacity and protective effects in chondrocytes in vitro and in in vivo rat OA models. Additionally, DHMP/M exhibits efficacious photoacoustic (PA) imaging for adjusting the therapy on demand. The RNA-Seq assay of rats further shows a significant reduction of TLR-2 in the OA cartilage, revealing that DHMP/M can protected OA from inflammation via TLR-2/MAPK/Akt signaling. Consequently, the present ROS/NIR dual-responsive melanin delivery platform together with PA imaging-monitoring provides a precise theranostic strategy for OA therapy.

The increasing worldwide pollution of nature waters with endocrine disrupting chemicals (EDCs), heavy metals and dyes has highlighted the need for versatile and effective removal approaches. In this study, a citric acid-crosslinked β-cyclodextrin polymer (CA-β-CD) was applied for simultaneous adsorption of bisphenol A (BPA), methylene blue (MB) and Cu2+, typical pollutants of EDCs, dyes and heavy metals, respectively. In a monocomponent system, the adsorption behaviors exhibited a monolayer maximum adsorption capacity (qm) of 0.3636 mmol/g for BPA, and a heterogeneous qm of 0.9229 and 0.9155 mmol/g for MB and Cu2+, respectively. The multicomponent experiment indicated that BPA and MB adsorptions onto CA-β-CD were independent from each other, whereas MB and Cu2+ competed over the same sites. An adsorption mechanism was proposed: each component of CA-β-CD played an essential role, the cyclodextrin cavities contributed to entrapment of non-polar BPA, and the surface carboxyl groups provided binding sites for polar MB and Cu2+. Adsorption performance of the polymer was unaffected by humic acid, a major component of natural organic matter. Overall, due to its green synthetic procedure, versatile and good adsorption performance, excellent recyclability and anti-jamming capacity, CA-β-CD has great potentials for practical applications in water purification.

Recent drug delivery nanosystems for cancer treatment still suffer from the poor tumor accumulation and low therapeutic efficacy due to the complex in vivo biological barriers. To resolve these problems, in this work, a novel gradient redox-responsive and two-stage rocket-mimetic drug nanocarrier is designed and constructed for improved tumor accumulation and safe chemotherapy. The nanocarrier is constructed on the basis of the disulfide-doped organosilica-micellar hybrid nanoparticles and the following dual-functional modification with disulfide-bonded polyethylene glycol (PEG) and amido-bonded polyethylenimine (PEI). First, prolonged circulation duration in the bloodstream is guaranteed due to the shielding of the outer PEG chains. Once the nanocarrier accumulates at the tumoral extracellular microenvironment with low glutathione (GSH) concentrations, the first-stage redox-responsive behavior with the separation of PEG and the exposure of PEI is triggered, leading to the improved tumor accumulation and cellular internalization. Furthermore, with their endocytosis by tumor cells, a high concentration of GSH induces the second-stage redox-responsiveness with the degradation of silsesquioxane framework and the release of the encapsulated drugs. As a result, the rocket-mimetic drug carrier displays longer circulation duration in the bloodstream, higher tumor accumulation capability, and improved antitumor efficacy (which is 2.5 times higher than that with inseparable PEG). It is envisioned that the rocket-mimetic strategy can provide new solutions for improving tumor accumulation and safety of nanocarriers in further cancer chemotherapy.

The development of hybrid particles for tumor diagnosis and therapy has received considerable attention because they are capable of combining tumor diagnosis and treatment concurrently. So far hybrid particles for efficient and safe tumor theranostics are still very limited. Herein we have designed a new type of hybrid particles and evaluated its potential to be used in image-guided cancer diagnosis and therapy without the need of any toxic anticancer or contrast agents. The hybrid particles, consist of magnetic nanoparticles which are embedded in the poly(methyl methacrylate) (PMMA) cores and gold shells on chitosan (CTS) (γ-Fe2O3 @PMMA/CTS@Au). The hybrid particles were synthesized through initial formation of the core–shell structured γ-Fe2O3 @PMMA/CTS particles containing approximately 20% loading of magnetic nanoparticles. A gold layer was then built on top of the core–shell magnetic particles via a reduction of gold salt by amines from the chitosan assisted with the reducing agent NaBH4, followed by growing to complete gold shells in the presence of ascorbic acid (42.6% Au content). The properties of the composite particles including their chemical composition, morphology, particle size, size distribution, surface charge, magnetic responsiveness and photothermal ability were systematically characterized. The potential application of the γ-Fe2O3 @PMMA/CTS@Au hybrid particles in tumor diagnosis and therapy was assessed in vitro and in vivo using 4T1 tumor cells and 4T1 tumor-bearing mice through combining magnetic targeting, photoacoustic (PA)/computed tomography (CT) imaging and photothermal therapy. Results suggest that the γ-Fe2O3 @PMMA/CTS@Au particles can serve as a multifunctional tumor theranostic nanoplatform for magnetically targeted photothermal therapy. Breast cancer has been effectively eliminated without the use of any anticancer drugs or contrast agents. Therefore, this type of core–shell hybrid particles represents a new composite particle design for effective and safe tumor theranostics.

Nanomaterials have attracted increased attention because of their excellent drug-carrying capacity. However, these nanomaterials are rarely used in the treatment of metabolic diseases. Liraglutide , a glucagon-like peptide-1 receptor agonist, has been widely used in the treatment of type 2 diabetes mellitus (T2DM). Furthermore, fibroblast growth factor 21 (FGF-21) has been found to improve glucose metabolism and insulin resistance (IR). To investigate whether these two molecules have synergistic effects in vivo , we developed a novel drug delivery system using amino-functionalized and embedded dual-mesoporous silica nanoparticles (N-EDMSNs) to simultaneously carry liraglutide and FGF-21, and observed their biological effects. The resultant N-EDMSNs possessed unique hierarchical porous structures consisting of open large pores (>10 nm) and small mesopores (~2.5 nm) in the silica framework, highly positively charged surfaces and good disperisity in aqueous solution. We found that N-EDMSNs had a high loading capacity for exogenous genes and low toxicity to Hepa1-6 cells. Moreover, N-EDMSNs can simultaneously carry FGF-21 plasmids and liraglutide and successfully transfect them into Hepa1-6 cells. The transfection efficiency of N-EDMSNs was higher than that of Lipofectamine 2000 in vitro. In mice experiments, N-EDMSNs/pFGF21 treatment resulted in higher FGF-21 expression in the liver than pFGF21 treatment with hydrodynamic delivery . Compared with both pFGF21 and liraglutide, N-EDMSNs/pFGF21/Lira treatment significantly reduced the food intake, body weight, and blood glucose; increased the energy expenditure and improved hepatic IR in high-fat diet (HFD)-fed mice. Our results demonstrated that the biological effects of N-EDMSNs/pFGF21/Lira complexes were better than those of pFGF21 combined with liraglutide in vivo.

A scalable synthesis of magnetic core–shell nanocomposite particles, acting as a novel class of magnetic resonance (MR) contrast agents, has been developed. Each nanocomposite particle consists of a biocompatible chitosan shell and a poly(methyl methacrylate) (PMMA) core where multiple aggregated γ-Fe2O3 nanoparticles are confined within the hydrophobic core. Properties of the nanocomposite particles including their chemical structure, particle size, size distribution, and morphology, as well as crystallinity of the magnetic nanoparticles and magnetic properties were systematically characterized. Their potential application as an MR contrast agent has been evaluated. Results show that the nanocomposite particles have good stability in biological media and very low cytotoxicity in both L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). They also exhibited excellent MR imaging performance with a T2 relaxivity of up to 364 mMFe−1 s−1. An in vivo MR test performed on a naked mouse bearing breast tumor indicates that the nanocomposite particles can localize in both normal liver and tumor tissues. These results suggest that the magnetic core–shell nanocomposite particles are an efficient, inexpensive and safe T2-weighted MR contrast agent for both liver and tumor MR imaging in cancer therapy.

Recently, nanoparticle-triggered in situ catalytic Fenton/Fenton-like reaction is widely explored for tumor-specific chemodynamic therapy (CDT). However, despite the great potential of CDT in tumor treatment, insensitive response to the relatively high pH of the tumor sites and the insufficient intratumoral H2 O2 level leads to limited efficiency of most Fenton/Fenton-like reactions, which greatly imped its clinical conversion. This paper reports the fabrication of Fenton-type bimetallic peroxides for ultrasensitive chemodynamic therapy with high pH-activated, synergistic effect/H2 O2 self-supply-mediated cascade Fenton chemistry for the first time. The observations reveal that these bimetallic peroxides exhibit an ultrasensitive acid-activated decomposition-mediated Fenton-like reaction at the relatively high pH of 6.5-7.0, accompanied with highly increased •OH generation efficiency (especially, 40-60-fold increase at pH 7.0) by the metal-mediated synergistic effect-enhanced Fenton chemistry as well as in situ self-generated H2 O2 supplement. Moreover, the bimetallic peroxides exhibit high tumor accumulation which along with a high-efficiency tumor catalytic-therapeutic with negligible side effects in vivo. Developing these novel bimetallic peroxides, together with the already demonstrated capacity of the key metals (Fe, Mn, Cu, etc.) for magnetic resonance imaging or photodynamic/immune-enhanced therapy, will propel interest in development of smart high-efficiency nanoplatform for cancer theranostics.

Porous materials have distinct advantages in catalysis, adsorption, and biomedicine due to their excellent loading spaces and high stability. However, the precise control on the sizes and hierarchies/distributions of pore channels in a nanoscale matrix is still challenging. Herein, a simple but efficient hydrophobicity-induced electrostatic interfacial self-assembly (HEISA) strategy is developed to synthesize porous silica nanospheres (PSNs) with large tunable pore sizes (10–30 nm) and pore hierarchies (dual-pores and tri-modal pores). In the synthesis processes, hydrophobic homopolymers polystyrene (PS) can not only act as pore-swelling agents for the enlargement of pore channels up to ∼30 nm, but also induce the evolution of pore hierarchies from dual-modal PSNs to tri-modal PSNs. By employing hydrophobic homopolymers as hydrophobicity-induced agents, a “homopolymer-mediated enlarging mesopore and creating macropore” mechanism is proposed. The degradation behaviors of PSNs in phosphate buffer saline (PBS) exhibited a pore size- and concentration-dependent manners. Furthermore, the maximum loading amount of PSNs reached 143 ± 46 mg/g of bovine serum albumin (BSA) and 258 ± 30 mg/g of catalase (CAT). More interestingly, a magnetic functionalized tri-modal PSNs with unique “vesicular” morphology was obtained by employing hydrophobic magnetite nanocrystals as hydrophobicity-induced agents via this HEISA approach, which showed an ultra-high transverse relaxivity up to 670.5 mMFe−1·S−1 in the T2-weighted magnetic resonance imaging. We therefore conceive that this proposed HEISA methodology provides a general pathway for developing ultra-large-pore mesoporous silica nanoparticles and hierarchical pore structures with various compositions and functions, further allowing the improvement of properties in biomedicine, catalysis, energy conversion and storage and adsorption or separation.

Bone morphogenetic protein (BMP)-9 has been associated with insulin resistance and type 2 diabetes mellitus. However, methods for delivering exogenous BMP-9 genes in vivo are lacking. In this study, we developed a gene delivery system using polyethyleneimine (PEI)-based core-shell nanoparticles (PCNs) as gene delivery carriers, and investigated the effectiveness and safety for delivery of the shBMP-9 gene. PCNs possessed a well-defined core-shell nanostructure with hydrophobic polymer cores and dense PEI shells of uniform particle size and highly positively charged surfaces. In vitro evaluation suggested that PCNs had high loading capacity for exogenous genes and low cytotoxicity toward hepatocytes. The transfection efficiency of PCNs/pENTR-shBMP9 complexes was higher than that of commercial lipofectamine 2000/shBMP9. In vivo studies showed that PCNs/pENTR-shBMP9 transfection led to a significant decrease in hepatic BMP9 expression compared with pENTR-shBMP9 transfection. Under high fat diet (HFD) feeding, PCNs/pENTR-shBMP9 mice exhibited aggravated glucose and insulin tolerance. At a molecular level, PCNs/pENTR-shBMP9 mice displayed elevated PEPCK protein levels and lower levels of InsR and Akt phosphorylation than pENTR-shBMP9 mice. These results suggest that the biological effects of PCNs/pENTR-shBMP9 in vivo are much more effective than those of pENTR-shBMP9. Therefore, the polyethyleneimine (PEI)-based core-shell nanoparticle can be applied as promising nanocarriers for effective and safe gene delivery.

Exploring innovative technologies to precisely quantify biomolecules is crucial but remains a great challenge for disease diagnosis. Unfortunately, the humoral concentrations of most biotargets generally vary within rather limited scopes between normal and pathological states, while most literature-reported biosensors can detect large spans of targets concentrations, but are less sensitive to small concentration changes, which consequently make them mostly unsatisfactory or even unreliable in distinguishing positives from negatives. Herein, a novel strategy of precisely quantifying the small concentration changes of a certain biotarget by editing the dynamic ranges and sensitivities of a lanthanide-based metal-organic framework (Eu-ZnMOF) biosensor is reported. By elaborately tailoring the biosensor's structure and surface areas, the tunable Eu-ZnMOF is developed with remarkably enhanced response slope within the "optimized useful detection window," enabling it to serve as a powerful signal amplifier (87.2-fold increase) for discriminating the small concentration variation of urinary vanillylmandelic acid (an early pathological signature of pheochromocytoma) within only three times between healthy and diseased subjects. This study provides a facile approach to edit the biosensors' performances through structure engineering, and exhibits promising perspectives for future clinical application in the non-invasive and accurate diagnosis of severe diseases.

Supramolecular amphiphilic vesicles are promising carriers in tumor therapy due to their excellent loading capabilities for both hydrophilic and hydrophobic cargos, especially for biomacromolecules such as proteins, enzymes and plasmids. However, the poor circulating stability and unsatisfied therapeutic efficiency greatly limit their in vivo applications. To address these issues, herein, we design and develop a new kind of GSH/pH dual-responsive supramolecular hybrid vesicles (SHVs) to encapsulate and deliver simultaneously biomacromolecule glucose oxidase (GOD) and chemotherapeutic drug docetaxel (DTX) for synergistic enzymatic/chemo-tumor therapy. The SHVs are constructed by the self-assembly of β-CD-poly(e-caprolactone), ferrocene-poly (acrylic acid) and pillar [5] arenes via the terminal β-CD/Fc host-guest interaction, followed by cross-linking with 3-mercaptopropyltrimethoxysilane and poly (ethylene glycol) modification. As a vehicle for both hydrophilic and hydrophobic cargos, the resulting GOD/DTX co-loaded SHVs exhibit excellent synergistic enzymatic/chemo-tumor therapeutic ability with a combination index (CI = 0.285) of GOD and DTX in cellular level and high tumor inhibitory rate of 95.3% in vivo. Consequently, the resulting hybrid vesicles can be used as efficient and safe carriers for biomacromolecules in further cancer therapy.

Heavy-metal-free fluorescent nanoparticles with high photostability and low toxicity are highly desirable as imaging probes for biological applications. Here, a novel synthetic strategy to prepare ultrabright multi-carbon dot cross-linked PEI particles, namely CDs@PEI, through self-assembly of hydrophobically modified PEI and in situ generations of carbon dots within residual monomer-swollen micelles is reported. The resulting particles consist of numerous carbon dots, which are individually and homogeneously embedded within the PEI network, and have an average hydrodynamic diameter of approximately 100 nm with ζ-potential above +35 mV. The CDs@PEI particles possess the synergistic effect of photoluminescent carbon dot and crosslink-enhanced emission of PEI, giving the particles superior optical properties such as high fluorescence quantum yield (up to 66%) in the aqueous system, excitation-dependent emission phenomenon, stable fluorescence in a wide pH range, and resistance to photobleaching.

A pillar[5]arene-based nonionic polyrotaxane (PR) with star-poly(ε-caprolactone) ( S-PCL) as the axle, pillar[5]arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with β-cyclodextrin end-capped pH-stimulated poly(acrylic acid) (CD-PAA) via a host-guest interaction to form the supramolecular pseudoblock polymer PR-PAA. This supramolecular pseudoblock polymer could self-assemble in aqueous solution to produce PR-PAA-based supramolecular vesicular nanoparticles (PR-SVNPs), which present significantly enhanced drug loading capacity (DLC, 45.6%) of DOX, much higher than those of superamphiphiles (PCL-PAA, 17.1%). Such a high DLC of PR-SVNPs can be most probably attributed to the greatly decreased crystallinity of PCL in PR. Moreover, the loaded drugs could be selectively released in an acidic microenvironment-responsive manner. Compared to free DOX, the DOX-loaded PR-SVNPs (DOX@PR-SVNPs) shows much enhanced cellular uptake and cytotoxicity against the SMMC-7721. More importantly, thanks to the enhanced permeability and retention (EPR) effect, DOX@PR-SVNPs exhibits appealing features such as extremely low toxicity, highly efficient intratumoral accumulation and substantial antitumor efficacy in vivo.

Efficient morphology modulation of a red AIEgen from pristine microsized rods to nanospheres is achieved via encapsula ting QM-2 (quinolinemalononitrile-2) into hybrid micelles. This novel reagent shows great potential in tumor-targeted bioimaging because of its monodispersion in aqueous systems, the uniform diameter of ≈30 nm, enhanced fluorescence brightness with a large Stokes shift of 190 nm, and strongly increased biocompatibility and photostability.

The currently available techniques for transferring exogenous genes into macrophages, especially the targeted import of exogenous genes into Kupffer cells (KCs) in vivo, are inefficient and achieve only low targeting. Novel Large-Pore Mesoporous Silica Nanospheres (LPMSNs) may be a promising gene transfection agent for KCs because of their superior biodegradation and hypotoxic characteristics, as well as their ability to retain the biological function of KCs and the high loading-rate of exogenous plasmid. LPMSNs were able to completely adsorb shRNA-TRAF3 (tumor necrosis factor receptor-associated factor-3) plasmid at a mass ratio as low as 30:1, and exhibited a low cytotoxicity for KCs. LPMSNs were detected in KC cytoplasm in vitro, and transmission electron microscopy (TEM) revealed that they were present only in KCs in liver tissue in vivo. The max KC transfection efficiency with LPMSNs was 34.8± 0.07%, as evaluated using flow cytometry, and the protein and mRNA levels of TRAF3 were significantly inhibited (P