Large-scale synthesis of monodisperse ultrasmall metal ferrite nanoparticles as well as understanding the correlations between chemical composition and MR signal enhancement is critical for developing next-generation, ultrasensitive T magnetic resonance imaging (MRI) nanoprobes. Herein, taking ultrasmall MnFeO nanoparticles (UMFNPs) as a model system, we report a general dynamic simultaneous thermal decomposition (DSTD) strategy for controllable synthesis of monodisperse ultrasmall metal ferrite nanoparticles with sizes smaller than 4 nm. The comparison study revealed that the DSTD using the iron-eruciate paired with a metal-oleate precursor enabled a nucleation-doping process, which is crucial for particle size and distribution control of ultrasmall metal ferrite nanoparticles. The principle of DSTD synthesis has been further confirmed by synthesizing NiFeO and CoFeO nanoparticles with well-controlled sizes of ∼3 nm. More significantly, the success in DSTD synthesis allows us to tune both MR and biochemical properties of magnetic iron oxide nanoprobes by adjusting their chemical composition. Beneficial from the Mn dopant, the synthesized UMFNPs exhibited the highest r relaxivity (up to 8.43 mM s) among the ferrite nanoparticles with similar sizes reported so far and demonstrated a multifunctional T MR nanoprobe for in vivo high-resolution blood pool and liver-specific MRI simultaneously. Our study provides a general strategy to synthesize ultrasmall multicomponent magnetic nanoparticles, which offers possibilities for the chemical design of a highly sensitive ultrasmall magnetic nanoparticle based T MRI probe for various clinical diagnosis applications.

Recently, Gd3+-based NIR persistent luminescence nanoparticles have been proposed as highly promising multimodal nanoprobes for full-scale visualization medical techniques in early diagnosis of cancer. However, they still face with some problems, such as hampering further functionalization for the loss of available surface, shortening plasma half-life of the probe caused by inevitable size increase, and reducing SNR because of significant persistent intensity loss. In this study, a novel core–shell structure Gd3+-based NIR persistent luminescence multimodal probe ZGOCS@MSNs@Gd2O3 for T1-weighted MR imaging and NIR persistent luminescence imaging was successfully synthesized using MSNs as the reaction vessels for ZGOCS nanoparticles and the core for Gd2O3 shell. Compared with previously reported Gd3+-based NIR persistent luminescence-based multimodal nanoprobes, the as-prepared nanoparticles enable surface available, no persistent intensity loss and only a slight size increase. Moreover, this multifunctional nanoprobe not only retains excellent NIR persistent luminescence properties with rechargeable ability, but also possesses high longitudinal relaxivity via the Gd2O3 shell, positioning ZGOCS@MSNs@Gd2O3 as highly promising nanoprobe for future multimodal bioimaging.

Lead halide perovskite nanocrystals (NCs) have been widely investigated owing to their potential applications as optoelectronic devices. However, these materials suffer from poor water stability, which make them impossible to be applied in biomedicine. Here, insoluble CsPbBr3/CsPb2Br5 composite NCs were successfully synthesized via simple water-assisted chemical transformation of perovskite NCs. Water plays two key roles in this synthesis: (i) stripping CsBr from CsPbBr3/Cs4PbBr6 and (ii) modifying the coordination number of Pb2+ (six in CsPbBr3 and Cs4PbBr6 vs eight in CsPb2Br5). The as-prepared CsPbBr3/CsPb2Br5 composite NCs not only retain the photoluminescence quantum yield (up to 80%) and a narrow full width to half-maximum of 16 nm, but also present excellent water stability and low cytotoxicity. With these properties, the CsPbBr3/CsPb2Br5 composite NCs were demonstrated as efficient fluorescent probes in live HeLa cells. We believe that our finding not only provides a new method to prepare insoluble, narrow-band, and brightly luminescent CsPbBr3/CsPb2Br5 composite NCs, but also extend the potential applications of lead halides in biomedicine.

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.

The development of a highly efficient, low-toxicity, ultrasmall ferrite nanoparticle-based T 1 contrast agent for high-resolution magnetic resonance imaging (MRI) is highly desirable. However, the correlations between the chemical compositions, in vitro T 1 relaxivities, in vivo nano-bio interactions and toxicities remain unclear, which has been a challenge in optimizing the in vivo T 1 contrast efficacy. Methods : Ultrasmall (3 nm) manganese ferrite nanoparticles (Mn x Fe 3-x O 4 ) with different doping concentrations of the manganese ions (x = 0.32, 0.37, 0.75, 1, 1.23 and 1.57) were used as a model system to investigate the composition-dependence of the in vivo T 1 contrast efficacy. The efficacy of liver-specific contrast-enhanced MRI was assessed through systematic multiple factor analysis, which included the in vitro T 1 relaxivity, in vivo MRI contrast enhancement, pharmacokinetic profiles (blood half-life time, biodistribution) and biosafety evaluations ( in vitro cytotoxicity testing, in vivo blood routine examination, in vivo blood biochemistry testing and H&E staining to examine the liver). Results : With increasing Mn doping, the T 1 relaxivities initially increased to their highest value of 10.35 mM -1 s -1 , which was obtained for Mn 0.75 Fe 2.25 O 4 , and then the values decreased to 7.64 m M -1 s -1 , which was obtained for the Mn 1.57 Fe 1.43 O 4 nanoparticles. Nearly linear increases in the in vivo MRI signals (ΔSNR) and biodistributions (accumulation in the liver) of the Mn x Fe 3-x O 4 nanoparticles were observed for increasing levels of Mn doping. However, both the in vitro and in vivo biosafety evaluations suggested that Mn x Fe 3-x O 4 nanoparticles with high Mn-doping levels (x > 1) can induce significant toxicity. Conclusion : The systematic multiple factor assessment indicated that the Mn x Fe 3-x O 4 (x = 0.75-1) nanoparticles were the optimal T 1 contrast agents with higher in vivo efficacies for liver-specific MRI than those of the other compositions of the Mn ...