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The numerous biological barriers, which limit pharmacotherapy of pancreatic carcinoma, including inadequate drug accumulation in the tumor environment, a dense extracellular matrix (ECM) and efficient drug‐efflux mechanisms, illustrate the requirement of multifunctional delivery systems to overcome the individual barriers at the right place at the right time. Herein, a space–time conversion vehicle based on covalent organic framework (COF)‐coated mesoporous silica nanospheres (MSN) with a sandwiched polyethyleneimine (PEI) layer (MPCP), is designed. The space‐specific drugs‐loaded vehicle (MGPPCLP) is obtained by separately incorporating a chemotherapeutic agent (gemcitabine, G) into the MSN core, a P glycoprotein inhibitor (LY 335979, P) into the PEI layer, and an extracellular matrix disruptor (losartan, L) into the COF shell. Thereafter, a programmed drug delivery is achieved via the ordered degradation from COF shell to MSN core. Sequential release of the individual drugs, synergized with a change of nanoparticle surface charge, contribute to an obvious extracellular matrix distraction, distinct drug efflux inhibition, and consequently enhance chemotherapeutic outcomes in pancreatic carcinoma. This MPCP‐based vehicle design suggests a robust space–time conversion strategy to achieve programmed multi‐drugs delivery and represents a new avenue to the treatment of pancreatic carcinoma by overcoming extracellular matrix and drug reflux barriers. [ABSTRACT FROM AUTHOR]

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0 ± 3.2 nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant ( K a ) and apparent permeability coefficients ( P app ) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Synergizing the sensitive circulating tumor cell (CTC) capture, detection, release and the specific magnetic resonance/fluorescence (MR/FL) imaging for accurate cancer diagnosis is of great importance for cancer treatment. Herein, EcoR 1-responsive complementary pairing of two ssDNA with a fluorescent P 0 aptamer, which can specifically bind with the overexpressed MUC1 protein on cancer cells, was covalently modified to SiO 2 @C-coated magnetic nanoparticles for preparing a special nanoparticle-mediated FL turn-on aptasensor (FSC-D-P 0). This aptasensor can selectively capture/enrich CTC and thus achieve sensitive CTC detection/imaging in even the blood due to its stable targeting, unique magnetic properties and the regulated interactions between the quencher and the fluorescent groups. Meanwhile, FSC-D-P 0 can release the captured CTC for further downstream analysis upon the EcoR 1 enzyme-triggered cleavage of the double-stranded DNA (dsDNA). Most importantly, this aptasensor can distinctly avoid false positivity of MRI via multiple targeting mechanisms. Thus, the sensitive CTC capture, detection, release and accurate MR/FL imaging were synergistically combined into a single platform with good biocompatibility, promising a robust pattern for clinical tumor diagnosis in vitro and in vivo. [ABSTRACT FROM AUTHOR]

An ideal cancer diagnostic probe should possess precise tumor-targeted accumulation with negligible sojourn in normal tissues. Herein, tumor cell-derived carbon nanodots (C-CNDU87 and C-CNDHepG2) about 3~7 nm were prepared by a solvothermal method with stable fluorescence and negligible cytotoxicity. More interestingly, due to the differences in gene expression of cancers, C-CND structurally mimicked the corresponding precursors during carbonization in which carbon nanodots were functionalized with α-amino and carboxyl groups with different densities on their edges. With inherent homology and homing effect, C-CND were highly enriched in precursor tumor tissues. Mechanistic studies showed that under the mediation of the original configuration of α-amino and carboxyl groups, C-CND specifically bound to the large neutral amino acid transporter 1 (LAT1, overexpressed in cancer cells), achieving specific tumor fluorescence imaging. This work provided a new vision about tumor cell architecture-mimicked carbon nanodots for tumor-targeted fluorescence imaging. [ABSTRACT FROM AUTHOR]

Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T 10 peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy. [ABSTRACT FROM AUTHOR]

A 3D porous composite LiFePO 4 /carbon material (LFP/RE) is synthesized via a facile method of the in-situ polymerization of hydroquinone-formaldehyde resin accompanying with the precursor co-precipitation and the subsequent carbothermal reduction process. Such 3D porous LFP/RE exhibits high specific surface area of 92.75 m2 g−1 and high pore volume of 0.1456 cm3 g−1, which can effectively improve the lithium ion diffusion coefficient up to 1.07 × 10−12 cm2 s−1. At 0.1 C, the LFP/RE displays a splendid discharge capacity of 169.3 mAh g−1 approximating to the theoretical specific capacity of LiFePO 4. More importantly, when the rate increases to 20 C, the discharge capacity can still deliver to 105.8 mAh g−1 with an exceptionally outstanding retention of 93.8% after 500 charge-discharge cycles. It is illustrated that the superior interconnected porous structure of LFP/RE can provide fast-speed electronic transferred super highway, which greatly augments the cycle and rate performances of lithium-ion batteries. • LFP/RE has a superior interconnected porous structure. • LFP/RE has an increased Li+ diffusion coefficient of 1.07 × 10−12 cm2 s−1. • LFP/RE exhibits 169.3 mAh g−1 (0.1 C) and 105.8 mAh g−1 (20 C). • LFP/RE has high tap density of 1.67 g cm−3. [ABSTRACT FROM AUTHOR]

Iridium(III) complexes show wide applications in biosensing and bioimaging, while Ir(III)-based Zn2+ probes are still rare and suffer from poor selectivity and low water solubility. In this work, we verified the phosphonate group as an efficient Zn2+ recognition moiety and developed a phosphonate-containing Ir(III) complex (Ir-BPA) as a water-soluble phosphorescent Zn2+ probe. Ir-BPA exhibited aggregation-induced emission enhancement (AIEE). Zn2+-binding also induced Ir-BPA aggregation, leading to enhanced phosphorescence and emission color changing from red to yellow. The binding mechanism was studied via spectra analysis, transmission electron microscope (TEM) images, and theoretical simulation. Ir-BPA was further employed in imaging intracellular Zn2+ level fluctuations via supplementary supply of Zn2+ source or endogenous release under oxidative stress. This work positively utilized AIEE properties of Ir(III) complexes in Zn2+ detection and broadened the strategies for developing water-soluble, AIE-active Ir(III) complexes for biological applications. • Phosphonate group as an efficient recognition moiety for Zn2+. • Phosphonate-containing Ir(III) complex is water soluble and AIEE-active. • Fluorescent imaging of intracellular labile Zn2+ release under oxidative stress. [ABSTRACT FROM AUTHOR]

Developing an all-in-one multimodal theranostic platform that can synergistically integrate sensitive photoacoustic (PA) imaging, enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) as well as the nano-enzyme activated chemodynamic therapy (CDT) presents a great challenge for the current nanomedicine design. Herein, a simple hydrothermal method was used to prepare porous molybdenum disulfide (MoS 2) nanoflowers. These nanoflowers were assembled by three dimensional (3D)-stacked MoS 2 nanosheets with plentiful pores and large surfaces, which thus exhibited enhanced photothermal conversion via light trapping and peroxidase (POD)-like activity via active defects exposure. Consequently, this 3D-MoS 2 nanostructure could be well-sealed by polyethylene glycol-polyethylenimine polymer modified with nucleolar translocation signal sequence of the LIM Kinase 2 protein (LNP) via strong electrostatic interaction, which not only benefited to stably deliver anticancer drug doxorubicin (DOX) into the tumor cells for pH/NIR-responsive chemotherapy, but also provided strong photoacoustic, photothermal performances and stimulated generation of reactive oxygen species (ROS) for imaging-guided PTT/PDT/CDT combined therapy. This work promised a simple all-in-one multimodal theranostic platform to augment the potential antitumoral therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Functionalizing black phosphorus nanosheet (BP) with efficient drug loading and endowing mesoporous silica nanomaterials with appropriate biodegradation for controllable tumor-targeted chemo-photothermal therapy are still urgent challenges. Herein, an ordered mesoporous silica-sandwiched black phosphorus nanosheet (BP@MS) with the vertical pore coating was prepared. The strategy could not only enhance the BP's dispersity and improve its doxorubicin (DOX)-loading efficiency, but also facilitate post-modification such as PEGylation and conjugation of targeting ligand, TKD peptide, yielding BSPT. A DOX-loaded BSPT-based system (BSPTD) showed heat-stimulative, pH-responsive, and sustained release manners. In vitro and in vivo results demonstrated that BSPTD had a delayed but finally complete degradation in physiological medium, contributing to an optimal therapeutic window and good biosafety. As a result, BSPTD can achieve an effective chemo-photothermal synergistic targeted therapy of tumor. Moreover, treating by BSPTD was found to be capable of remarkably inhibiting the lung metastasis of tumor, attributing to the photothermal degradation-facilitated secondary drug delivery. Our study provided a robust strategy to functionalize BP nanosheet and biodegrade the mesoporous silica for extended biomedical applications. [ABSTRACT FROM AUTHOR]