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We developed a theranostic approach exemplifying a concept called an "exchange method" that controls and "images" drug release from nanoparticles using magnetic resonance imaging-guided high-intensity focused ultrasound. The controllable amount of released drug and therapeutic efficacy can be self-reported by associated MRI contrast changes in solution and in cells. [ABSTRACT FROM AUTHOR]

Periodic high-intensity focused ultrasound modulation of a nanoparticle generates reversible MRI T1 relaxivity changes at the 1.5 mm3 focal point causing periodic T1-weighted signal changes. Fourier analysis extracts signal changes at the modulation frequency, and a modulation enhancement map spotlights the precise region of interest by increasing contrast almost 100-fold. [ABSTRACT FROM AUTHOR]

Creation of structural complexity by simple experimental control will be an attractive approach for the preparation of nanomaterials, as a classical bottom-up method is supplemented by a more efficient and more direct artificial engineering method. In this study, structural manipulation of MCM-41 type mesoporous silica is investigated by generating and imbedding hard magnetic CoFe2O4 nanoparticles into mesoporous silica. Depending on the heating rate and target temperature, mesoporous silica undergoes a transformation in shape to form hollow silica, framed silica with interior voids, or melted silica with intact mesostructures. Magnetism is governed by the major CoFe2O4 phase, and it is affected by antiferromagnetic hematite (α-Fe2O3) and olivine-type cobalt silicate (Co2SiO4), as seen in its paramagnetic behavior at the annealing temperature of 430 °C. The early formation of Co2SiO4 than what is usually observed implies the effect of the partial substitution of Fe in the sites of Co. Under slow heating (2.5 °C min−1) mesostructures are preserved, but with significantly smaller mesopores (d100 = 1.5 nm). In addition, nonstoichiometric CoxFe1−xO with metal vacancies at 600 °C, and spinel Co3O4 at 700 °C accompany major CoFe2O4. The amorphous nature of silica matrix is thought to contribute significantly to these structurally diverse and rich phases, enabled by off-stoichiometry between Si and O, and accelerated by the diffusion of metal cations into SiO4 polyhedra at an elevated temperature. [ABSTRACT FROM AUTHOR]

We report a two-photon-actuated cancer cell killing system that kills the cancer cells via drug delivery through multifunctional mesoporous silica nanogates. Two-photon-sensitive mesoporous organosilica (M2PS) nanocarriers were synthesized via the co-condensation of a silica precursor and a two-photon electron donor. The nanogates were constructed using a fast one-pot process at room temperature on the drug-loaded M2PS nanoparticles (NPs) with the bis(3-triethoxysilylpropyl)disulfide precursor. One and two-photon-actuated cargo releases from the M2PS nanogates were successfully monitored in aqueous solutions. Furthermore, the cellular uptake in MCF-7 cells was demonstrated via two-photon fluorescence imaging of the NPs, which were then applied successfully for drug delivery in cells. [ABSTRACT FROM AUTHOR]

A series of magnetically active ferrite nanoparticles (NPs) are prepared by using Mn oxide NPs as seeds. A Verwey transition is identified in Fe3O4 NPs with an average diameter of 14.5 nm at 96 K, where a sharp drop of magnetic susceptibility occurs. In MnFe2O4 NPs, a spin glass-like state is observed with the decrease in magnetization below the blocking temperature due to the disordered spins during the freezing process. From these MnFe2O4 NPs, MnFe2O4@MnxFe1−xO core–shell NPs are prepared by seeded growth. The structure of the core is cubic spinel (Fd3̅m), and the shell is composed of iron–manganese oxide (MnxFe1−xO) with a rock salt structure (Fm3̅m). Moiré fringes appear perpendicular to the 〈110〉 directions on the cubic shape NPs through the plane-matched epitaxial growth. These fringes are due to the difference in the lattice spacings between MnFe2O4 and MnxFe1−xO. Exchange bias is observed in these MnFe2O4@MnxFe1−xO core–shell NPs with an enhanced coercivity, as well as the shift of hysteresis along the field direction. [ABSTRACT FROM AUTHOR]

The charge transfer excited state of a mechanically interlocked [2]rotaxane (R4+) with a donor 1,5-dioxynaphthalene (DNP) unit in the rod and the acceptor cyclobis(paraquat-p-phenylene) (CBPQT4+) ring component, along with the analogous non-interlocked [2]pseudorotaxane (P4+), is studied by resonance Raman spectroscopy and electronic absorption spectroscopy. Resonance Raman excitation profiles are obtained, calculated quantitatively using time-dependent theoretical methods, and interpreted with the assistance of DFT calculations. The active vibrational modes are consistent with an electron transfer from the HOMO centered on the DNP unit to the LUMO on the CBPQT4+ring. Displacement vectors of highly distorted modes agree with the bonding changes predicted from the MO nodal pattern. Subtle changes in the frequency of some modes in the free components compared with those in R4+are observed. The largest distortions are found for modes involving ring breathing in the DNP unit of the rod and the paraquat units of the CBPQT4+ring. The individual mode contributions to the vibrational reorganization energy, as well as the total vibrational reorganization energy, are calculated. Very similar values of λvfor R4+and P4+are calculated (∼2910 cm−1), indicating that the mechanical stoppers in the interlocked system do not significantly affect the excited state properties of R4+compared with P4+. [ABSTRACT FROM AUTHOR]

A [2]pseudorotaxane-based mechanised nanoparticle system, which operates within an aqueous acidic environment, has been prepared and characterised; this integrated system affords both water-soluble stalk and ring components in an effort to improve the biocompatibility of these promising new drug delivery vehicles. [ABSTRACT FROM AUTHOR]

A potent class of isoquinoline-based α-N-heterocyclic carboxaldehyde thiosemicarbazone (HCT) compounds has been rediscovered; based upon this scaffold, three series of antiproliferative agents were synthesized through iterative rounds of methylation and fluorination modifications, with anticancer activities being potentiated by physiologically relevant levels of copper. The lead compound, HCT-13 , was highly potent against a panel of pancreatic, small cell lung carcinoma, prostate cancer, and leukemia models, with IC 50 values in the low-to-mid nanomolar range. Density functional theory (DFT) calculations showed that fluorination at the 6-position of HCT-13 was beneficial for ligand-copper complex formation, stability, and ease of metal-center reduction. Through a chemical genomics screen, we identify DNA damage response/replication stress response (DDR/RSR) pathways, specifically those mediated by ataxia-telangiectasia and Rad3-related protein kinase (ATR), as potential compensatory mechanism(s) of action following HCT-13 treatment. We further show that the cytotoxicity of HCT-13 is copper-dependent, that it promotes mitochondrial electron transport chain (mtETC) dysfunction, induces production of reactive oxygen species (ROS), and selectively depletes guanosine nucleotide pools. Lastly, we identify metabolic hallmarks for therapeutic target stratification and demonstrate the in vivo efficacy of HCT-13 against aggressive models of acute leukemias in mice., (This journal is © The Royal Society of Chemistry 2020.)

Here we report a new peptide modified mesoporous silica nanocontainer (PMSN) as a novel controlled release system. The peptides are part of a stimuli responsive nanovalve and ensure an efficient cellular uptake.