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Real‐time tracking of drug release from nanomedicine in vivo is crucial for optimizing its therapeutic efficacy in clinical settings, particularly in dosage control and determining the optimal therapeutic window. However, most current real‐time tracking systems require a tedious synthesis and purification process. Herein, a supramolecular nano‐tracker (SNT) capable of real‐time tracking of drug release in vivo based on non‐covalent host‐guest interactions is presented. By integrating multiple cavities into a single nanoparticle, SNT achieves co‐loading of drugs and probes while efficiently quenching the photophysical properties of the probe through host‐guest complexation. Moreover, SNT is readily degraded under hypoxic tumor tissues, leading to the simultaneous release of drugs and probes and the fluorescence recovery of probes. With this spatial and temporal consistency in drug loading and fluorescence quenching, as well as drug release and fluorescence recovery, SNT successfully achieves real‐time tracking of drug release in vivo (Pearson r = 0.9166, R2 = 0.8247). Furthermore, the released drugs can synergize effectively with fluorescent probes upon light irradiation, achieving potent chemo‐photodynamic combination therapy in 4T1‐bearing mice with a significantly improved survival rate (33%), providing a potential platform to significantly advance the development of nanomedicine and achieve optimal therapeutic effects in the clinic. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of methicillin‐resistant Staphylococcus aureus (MRSA) raise a critical need for alternative therapeutic options. New antibacterial drugs and targets are required to combat MRSA‐associated infections. Based on this study, celastrol, a natural product from the roots of Tripterygium wilfordii Hook. f., effectively combats MRSA in vitro and in vivo. Multi‐omics analysis suggests that the molecular mechanism of action of celastrol may be related to Δ1‐pyrroline‐5‐carboxylate dehydrogenase (P5CDH). By comparing the properties of wild‐type and rocA‐deficient MRSA strains, it is demonstrated that P5CDH, the second enzyme of the proline catabolism pathway, is a tentative new target for antibacterial agents. Using molecular docking, bio‐layer interferometry, and enzyme activity assays, it is confirmed that celastrol can affect the function of P5CDH. Furthermore, it is found through site‐directed protein mutagenesis that the Lys205 and Glu208 residues are key for celastrol binding to P5CDH. Finally, mechanistic studies show that celastrol induces oxidative stress and inhibits DNA synthesis by binding to P5CDH. The findings of this study indicate that celastrol is a promising lead compound and validate P5CDH as a potential target for the development of novel drugs against MRSA. [ABSTRACT FROM AUTHOR]

Vigorous development of electric vehicles is one way to achieve global carbon reduction goals. However, fires caused by thermal runaway of the power battery has seriously hindered large‐scale development. Adding thermal runaway retardants (TRRs) to electrolytes is an effective way to improve battery safety, but it often reduces electrochemical performance. Therefore, it is difficult to apply in practice. TRR encapsulation is inspired by the core–shell structures such as cells, seeds, eggs, and fruits in nature. In these natural products, the shell isolates the core from the outside, and has to break as needed to expose the core, such as in seed germination, chicken hatching, etc. Similarly, TRR encapsulation avoids direct contact between the TRR and the electrolyte, so it does not affect the electrochemical performance of the battery during normal operation. When lithium‐ion battery (LIB) thermal runaway occurs, the capsules release TRRs to slow down and even prevent further thermal runaway. This review aims to summarize the fundamentals of bioinspired TRR capsules and highlight recent key progress in LIBs with TRR capsules to improve LIB safety. It is anticipated that this review will inspire further improvement in battery safety, especially for emerging LIBs with high‐electrochemical performance. [ABSTRACT FROM AUTHOR]

CRISPR/dCas9 systems can precisely control endogenous gene expression without interrupting host genomic sequence and have provided a novel and feasible strategy for the treatment of cancers at the transcriptional level. However, development of CRISPR/dCas9‐based anti‐cancer therapeutics remains challenging due to the conflicting requirements for the design of the delivery system: a cationic and membrane‐binding surface facilitates the tumor accumulation and cellular uptake of the CRISPR/dCas9 system, but hinders the circulating stability in vivo. Here, a multistage delivery nanoparticle (MDNP) that can achieve tumor‐targeted delivery of CRISPR/dCas9 systems and restore endogenous microRNA (miRNA) expression in vivo is described. MDNP is designed as a core‐shell structure in which the shell is made of a responsive polymer that endows MDNP with the capability to present different surface properties in response to its surrounding microenvironment, allowing the MNDP overcoming multiple physiological barriers and delivering the payload to tumor tissues with an optimal efficiency. Systemic administration of MDNP/dCas9‐miR‐524 to tumor‐bearing mice achieved effective upregulation of miR‐524 in tumors, leading to the simultaneous interferences of multiple signal pathways related to cancer cell proliferation and presenting remarkable tumor growth retardation, suggesting the feasibility of utilizing MDNP to achieve tumor‐targeting delivery of CRISPR/dCas9 with sufficient levels to realize its therapeutic effects. A nonviral clustered regularly interspaced short palindromic repeat (CRISPR)/nuclease‐inactivated CRISPR associated protein 9 (dCas9) delivery system based on multistage delivery nanoparticle (MDNP) is developed, with the capability to present different surface properties in response to its surrounding microenvironment, allowing the MNDP to overcome multiple physiological barriers and achieve tumor‐targeted delivery of CRISPR/dCas9 systems to suppress tumor growth in mice. [ABSTRACT FROM AUTHOR]