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Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, a dual-stimulation activated turn-on T 1 imaging-based nanoparticulate system (DAS) is developed for mild photothermia (≈43 °C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticles, Fe 3 O 4 NPs) and a paramagnetic enhancer (Gd-DOTA complexes) are connected via the N6-methyladenine (m 6 A)-caged, Zn 2+ -dependent DNAzyme molecular device. The substrate strand of the DNAzyme contains one segment of Gd-DOTA complex-labeled sequence and another one of HSP70 antisense oligonucleotide. When the DAS is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m 6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled oligonucleotides. The restored T 1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterward, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy., (© 2023 Wiley-VCH GmbH.)

Photosensitizer in photodynamic therapy (PDT)  accumulates in both tumor and adjacent normal tissue due to low selective biodistribution, results in undesirable side effect with limited clinic application. Herein, an intelligent nanoplatform is reported that selectively acts as reactive oxygen species (ROS) scavenger in normal tissue but as ROS generator in tumor microenvironment (TME) to differentially control ROS level in tumor and surrounding normal tissue during PDT. By down-regulating the produced ROS with dampened cytokine wave in normal tissue after PDT, the nanoplatform reduces the inflammatory response of normal tissue in PDT, minimizing the side effect and tumor metastasis in PDT. Alternatively, the nanoplatform switches from ROS scavenger to generator through the glutathione (GSH) responsive degradation in TME, which effectively improves the PDT efficacy with reduced GSH level and amplified oxidative stress in tumor. Simultaneously, the released Mn ions provide real-time and in situ signal change of magnetic resonance imaging (MRI) to monitor the reversal process of catalysis activity and achieve accurate tumor diagnosis. This TME-responsive ROS scavenger/generator with activable MRI contrast may provide a new dimension for design of next-generation PDT agents with precise diagnosis, high therapeutic efficacy, and low side effect., (© 2022 Wiley-VCH GmbH.)

Doping Mn (II) ions into iron oxide (IO) as manganese ferrite (MnIO) has been proved to be an effective strategy to improve T 1 relaxivity of IO nanoparticle in recent years; however, the high T 2 relaxivity of MnIO nanoparticle hampers its T 1 contrast efficiency and remains a hurdle when developing contrast agent for early and accurate diagnosis. Herein, we engineered the interfacial structure of IO nanoparticle coated with manganese ferrite shell (IO@MnIO) with tunable thicknesses. The Mn-doped shell significantly improve the T 1 contrast of IO nanoparticle, especially with the thickness of ∼0.8 nm. Compared to pristine IO nanoparticle, IO@MnIO nanoparticle with thickness of ∼0.8 nm exhibits nearly 2 times higher T 1 relaxivity of 9.1 mM -1 s -1 at 3 T magnetic field. Moreover, exclusive engineering the interfacial structure significantly lower the T 2 enhancing effect caused by doped Mn (II) ions, which further limits the impairing of increased T 2 relaxivity to T 1 contrast imaging. IO@MnIO nanoparticles with different shell thicknesses reveal comparable T 1 relaxation rates but obvious lower T 2 relaxivities and r 2 /r 1 ratios to MnIO nanoparticles with similar sizes. The desirable T 1 contrast endows IO@MnIO nanoparticle to provide sufficient signal difference between normal and tumor tissue in vivo. This work provides a detailed instance of interfacial engineering to improve IO-based T 1 contrast and a new guidance for designing effective high-performance T 1 contrast agent for early cancer diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tumor hypoxia and the tissue penetration limitation of excitation light hamper the widespread clinical use of photodynamic therapy. The development of new therapeutic strategies that can generate oxygen-independent free radicals without penetration depth limitation is of great demand. Herein, a novel magnetothermodynamic strategy for deep-seated tumor therapy is reported. In this system, a radical initiator (AIPH) was loaded into porous hollow iron oxide nanoparticles (PHIONs). Under the induction of an alternating magnetic field (AMF), PHIONs can generate heat to trigger the release and decomposition of AIPH, resulting in the generation of oxygen-independent alkyl radicals. The resulting alkyl radicals can effectively kill cancer cells under hypoxic conditions. More importantly, this magnetothermally triggered free-radical generator exhibits significant therapeutic efficacy for orthotopic liver tumors in a rat model. This magnetothermodynamic therapy strategy with the advantages of oxygen independence and no limitation of penetration depth holds great promise in deep-seated solid tumor treatment.

Persistent luminescence nanoparticles (PLNPs) have great potential for bioimaging because they can eliminate the tissue autofluorescence and improve the signal-to-noise ratio significantly. High-temperature calcination is a necessary process for the PLNPs to achieve high luminescence intensity and long afterglow time. However, high-temperature calcination usually results in uncontrollable morphology and poor homogeneity of PLNPs, which greatly limit their applications. Therefore, there is still a high demand to find a suitable method for synthesizing PLNPs with high luminescence intensity and long afterglow time while maintaining their monodispersed morphology. Herein, we report a facile silica template method to synthesize PLNPs with a kiwifruit-like structure that can tolerate high-temperature calcination. The as-prepared kiwifruit-like SiO 2 @ZnGa 2 O 4 :Cr 3+ @SiO 2 PLNPs have enhanced near-infrared persistent luminescence, uniform morphology and size, and good biocompatibility. Moreover, the SiO 2 @ZnGa 2 O 4 :Cr 3+ @SiO 2 PLNPs can be repeatedly activated by soft X-rays in situ and emit near-infrared persistent luminescence with long decay time, holding great potential for deep-tissue and long-term in vivo bioimaging. We believe that this study will open new perspectives for synthesizing high-performance PLNPs for optical imaging and diversified applications.

Hydrophobic nanoparticles have shown substantial potential for bioanalysis and biomedical applications. However, their use is hindered by complex phase transfer and inefficient surface modification. This paper reports a facile and universal strategy for phase transfer and surface biofunctionalization of hydrophobic nanomaterials using aptamer-pendant DNA tetrahedron nanostructures (Apt-tet). The Janus DNA tetrahedron nanostructures are constructed by three carboxyl group modified DNA strands and one aptamer sequence. The pendant linear sequence is an aptamer, in this case AS1411, known to specifically bind nucleolin, typically overexpressed on the plasma membranes of tumor cells. The incorporation of the aptamers adds targeting ability and also enhances intracellular uptake. Phase-transfer efficiency using Apt-tet is much higher than that achieved using single-stranded DNA. In addition, the DNA tetrahedron nanostructures can be programmed to permit the incorporation of other functional nucleic acids, such as DNAzymes, siRNA, or antisense DNA, allowing, in turn, the construction of promising theranostic nanoagents for bioanalysis and biomedical applications. Given these unique features, we believe that our strategy of surface modification and functionalization may become a new paradigm in phase-transfer-agent design and further expand biomedical applications of hydrophobic nanomaterials.

This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM(-1) S(-1), which is about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM(-1) S(-1)). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications.

Abstract: A three-dimensional (3D) Fe3O4/carbon material functionalized with amino and hydroxyl groups was synthesized by decomposing 2,4,5-trichlorophenol/ferrocene mixture in the presence of ammonia and polyethylene glycol in solvothermal conditions at 250°C for 30h by a one-step process. The 3D Fe3O4/carbon materials can be loaded with Pt nanoparticles without adding any reducing agent; Pt-loaded 3D Fe3O4/carbon hybrid materials have superior electrochemical catalytic activity toward methanol oxidation and the oxidation current density on them is nearly triple that on a commercial Pt/C catalyst. [Copyright &y& Elsevier]

Abstract: Homogeneous and monodisperse hollow carbon microspheres (HCMS) functionalized with amino and hydroxyl groups are synthesized by decomposing 2,4,6-tribromophenol/ferrocene mixture in the presence of ammonia via a one-step solvothermal process at 250°C for 24h. The effect of experimental conditions on the morphology of carbon microspheres has been investigated systematically. The surface of the HCMS is modified with amino and hydroxyl groups through the synthesis process as confirmed by infra-red spectroscopy and X-ray photoelectron spectroscopy. The pore-size distribution and the specific area of macropores are measured by nitrogen adsorption–desorption and mercury intrusion porosimetry. The as-synthesized HCMS has the high Brunauer–Emmett–Teller surface area of 289m2/g and macropores whose diameter is mostly larger than 100nm. To investigate the chemical reactivity of functionalized groups on the surface of HCMS, Au and Ag nanoparticles are successfully loaded onto HCMS by direct reduction of HAuCl4 or AgNO3 without adding any reducing agent. [Copyright &y& Elsevier]