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Milk‐derived extracellular vesicles (M‐EVs) are low‐cost, can be prepared in large quantities, and can cross the gastrointestinal barrier for oral administration. However, the composition of milk is complex, and M‐EVs obtained by different extraction methods may affect their oral delivery. Based on this, a new method for extracting M‐EVs based on cryogenic freezing treatment (Cryo‐M‐EVs) is proposed and compared with the previously reported acetic acid treatment (Acid‐M‐EVs) method and the conventional ultracentrifugation method (Ulltr‐M‐EVs). The new method simplifies the pretreatment step and achieves 25‐fold and twofold higher yields than Acid‐M‐EVs and Ulltr‐M‐EVs. And it is interesting to note that Cryo‐M‐EVs and Acid‐M‐EVs have higher cellular uptake efficiency, and Cryo‐M‐EVs present the best transepithelial transport effect. After oral administration of the three M‐EVs extracted by three methods in mice, Cryo‐M‐EVs effectively successfully cross the gastrointestinal barrier and achieve hepatic accumulation, whereas Acid‐M‐EVs and Ultr‐M‐EVs mostly reside in the intestine. The M‐EVs obtained by the three extraction methods show a favorable safety profile at the cellular as well as animal level. Therefore, when M‐EVs obtained by different extraction methods are used for oral drug delivery, their accumulation properties at different sites can be utilized to better deal with different diseases. Milk‐derived extracellular vesicles (M‐EVs) hold a very high potential for oral application. Different extraction methods will change the composition of M‐EVs and thus affect their oral properties. Here, the cryogenic freezing method is used to extract M‐EVs with high purity and highest yield. It can effectively cross the intestinal tract and accumulate in the liver after oral administration.

Metallic shape transformable materials hold big promise for improved intracellular therapy. However, until now, there have been rather limited biomedical practices for such materials, which is mainly attributed to their inherent uncontrolled morphological transformation, non-selective destruction, and difficult metabolization. Here, Ga-based liquid metal is found to exhibit remarkable transformation from sphere shape to cactus-like structure in micro-scale under freezing. Particularly, only cell membrane-encapsulated Ga particles (Ga/MPs) display dramatic shape variation in cooling under cryo-transmission electron microscopy (cryo-TEM). Following that, cryo-triggered Ga/MPs transformers are designed for effective endosomal escape via a physical mechanical strategy to disrupt the endosomal membrane, which leads to highly efficient cancer cell killing. Ga/MPs exhibit significant tumor growth inhibition and prolonged survival time according to the collaborative efficacy of cryoablation and endosomal escape mechanism, as well as high-resolution in vivocomputed tomography (CT) imaging. This study opens a versatile strategy based on Ga particle transformer to assist high-performance precise intracellular therapy in future tumor therapeutics.

•A hierarchical calcium carbonate-based nanodrug release system was fabricated.•The mechanism of nanomaterial reprogramming the immune microenvironment was revealed.•The therapeutic mechanisms and pathways of nanodrug release system was discovered.

Exosomes are nanosized extracellular vesicles (ranging from 30 to 120 nm) released from many cells that provide promising biomarkers for the noninvasive diagnosis of cancer. However, traditional exosome-isolation methods are tedious, nonstandardized, and require bulky instrumentation, thus limiting its clinical applications. In this paper, an anion-exchange (AE)-based isolation method was first proposed to isolate exosomes directly from plasma and cell-culture medium with AE magnetic beads within 30 min. Exosomes isolated with AE magnetic beads had higher recovery efficiency (>90%) and less protein impurities than those isolated by ultracentrifugation (UC). Prostate-cancer (PCa) exosomes in plasma were detected in a visual, label-free, and quantitative manner with aptamer-capped Fe3O4nanoparticles for the first time. The linear range of PCa exosomes was estimated from 0.4 × 108to 6.0 × 108particles/mL with a detection limit of 3.58 × 106particles/mL. The present study provides an efficient and practical approach for the rapid isolation and visible detection of exosomes, which is promising for the early diagnosis of PCa.

Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage structure. In addition, the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery system. Therefore, ferritin has shown a broad application prospect in the field of nanomedicine. In this perspective, we will describe ferritin‐based drug delivery system, ferritin‐based drug delivery system for tumor treatment, and future challenges in ferritin development. Hopefully, this perspective may inspire the future development of ferritin‐based drug delivery systems for tumor treatment. Ferritin has been widely used in drug delivery in recent years due to its unique spherical nanocage structure. In addition, the natural targeting and good biocompatibility of ferritin make it an excellent drug delivery system. Therefore, ferritin has shown a broad application prospect in the field of nanomedical medicine. In this perspective, we will describe ferritin‐based drug delivery system, ferritin‐based drug delivery system for tumor treatment, and future challenges in ferritin development. Hopefully, this perspective may inspire the future development of ferritin‐based drug delivery system for tumor treatment.

Liquid metals are increasingly applied in drug delivery, in vivoimaging, and biosensing. Herein, we describe a surface modification strategy, where cell membrane is introduced to encapsulate gallium (Ga) particles. We detail preparation steps of Ga microparticles by sonication, followed by Ga microparticles coating with purified tumor cell membranes and morphological assessment using TEM and cryo-TEM. We further describe cell uptake and establishment of tumor-bearing mouse models and steps to assess in vitrocytotoxicity and in vivoantitumor cryotherapy.