Inspired by highly efficient natural motors, synthetic micro/nanomotors are self-propelled machines capable of converting the supplied fuel into mechanical motion. A significant advance has been made ...in the construction of diverse motors over the last decade. These synthetic motor systems, with rapid transporting and efficient cargo towing abilities, are expected to open up new horizons for various applications. Utilizing emergent motor platforms for
in vivo
applications is one important aspect receiving growing interest as conventional therapeutic methodology still remains limited for cancer, heart, or vasculature diseases. In this review we will highlight the recent efforts towards realistic
in vivo
application of various motor systems. With ever booming research enthusiasm in this field and increasing multidisciplinary cooperation, micro/nanomotors with integrated multifunctionality and selectivity are on their way to revolutionize clinical practice.
This review summarizes recent progress in micro/nanomotors towards
in vivo
applications at cell, tissue and biofluid levels.
Inspired by the self‐migration of microorganisms in nature, artificial micro‐ and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. ...These self‐propelled micro‐ and nanomotors, designed either by top‐down or bottom‐up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro‐/nanosurgery. For these various applications, especially biomedical applications, regulating on‐demand the motion of micro‐ and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro‐ and nanomotors by different approaches.
On‐demand regulation of the motion of artificial micro‐ and nanomotors is essential for diverse applications. The recent progress made during the last decade to manipulate the motional behavior of micro‐ and nanomotors by various approaches (such as light, magnetic fields, ultrasound, electric fields, temperature, pH, chemotaxis, and the addition of chemicals) is discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Inspired by the highly versatile natural motors, artificial micro‐/nanomotors that can convert surrounding energies into mechanical motion and accomplish multiple tasks are devised. In the past few ...years, micro‐/nanomotors have demonstrated significant potential in biomedicine. However, the practical biomedical applications of these small‐scale devices are still at an infant stage. For successful bench‐to‐bed translation, biocompatibility of micro‐/nanomotor systems is the central issue to be considered. Herein, the recent progress in micro‐/nanomotors in biocompatibility is reviewed, with a special focus on their biomedical applications. Through close collaboration between researches in the nanoengineering, material chemistry, and biomedical fields, it is expected that a promising real‐world application platform based on micro‐/nanomotors will emerge in the near future.
The biocompatibility of artificial micro‐/nanomotors is essential for real‐world biomedical applications. Recent progress about biocompatible micro‐/nanomotor systems that are based on biocompatible framework materials, chemical fuels (e.g., water, glucose, urea, and acid), external fields (e.g., magnetic field, light, and ultrasound) and biohybrid, is discussed here.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Scope
Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The ...study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association.
Methods and results
This study includes 5405 participants with T2D who provided at least one 24‐h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio HR: 1.10; 95% confidence interval CI: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A, C‐reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD.
Conclusion
Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.
In this prospective cohort study of individuals with type 2 diabetes (T2D), higher ultraprocessed food (UPF) intakes are associated with increased risks of overall cardiovascular disease (CVD), coronary heart disease, and heart failure. The higher risk of overall CVD associated with higher UPF consumption possibly goes through pathways that include renal function, lipid metabolism, inflammation, and body weight. Our study supports the need to stress the importance of decreasing UPF intake in dietary guidelines for T2D patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Species of the genus of
Cistanche (Rou Cong Rong in Chinese) are perennial parasite herbs, and are mainly distributed in arid lands and warm deserts. As a superior tonic for the treatment of kidney ...deficiency, impotence, female infertility, morbid leucorrhea, profuse metrorrhagia and senile constipation,
Cistanche herbs earned the honor of “Ginseng of the desert”. Recently, there has been increasing scientific attention on Herba Cistanche for its remarkable bioactivities including antioxidation, neuroprotection, and anti-aging. The chemical constituents of
Cistanche plants mainly include volatile oils and non-volatile phenylethanoid glycosides (PhGs), iridoids, lignans, alditols, oligosaccharides and polysaccharides. Pharmacological studies show that PhGs are the main active components for curing kidney deficiency, antioxidation and neuroprotection; galactitol and oligosaccharides are the representatives for the treatment of senile constipation, while polysaccharides are responsible for improving body immunity. In this paper, the advances on the chemical constituents of
Cistanche plants and their corresponding analyses are reviewed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a ...diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Syndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which ...represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
The development of artificial nanomotor systems that are stimuli‐responsive is still posing many challenges. Herein, we demonstrate the self‐assembly of a redox‐responsive stomatocyte nanomotor ...system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli‐responsive nanomotors are cleaved. The specific bowl‐shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox‐responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.
Destruction on demand: A redox‐responsive stomatocyte nanomotor was developed by incorporating disulfide bridges between the hydrophilic PEG and hydrophobic PS moieties of the copolymer. When incubated in vitro with the endogenous reducing agent glutathione, the external PEG shells of the nanomotors are cleaved, which results in the loss of motion and can be used for drug release.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Understanding the direct interaction of nanostructures per se with biological systems is important for biomedical applications. However, whether nanostructures regulate biological systems by ...targeting specific cellular proteins remains largely unknown. In the present work, self‐assembling nanomicelles are constructed using small‐molecule oleanolic acid (OA) as a molecular template. Unexpectedly, without modifications by functional ligands, OA nanomicelles significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanism study reveals that OA nanomicelles interact with PSMA6 to dynamically modulate its N‐terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome. Subsequently, OA nanomicelles accelerate the degradation of several crucial proteins, thus potently driving cancer cell pyroptosis. For translational medicine, OA nanomicelles exhibit a significant anticancer potential in tumor‐bearing mouse models and stimulate immune cell infiltration. Collectively, this proof‐of‐concept study advances the mechanical understanding of nanostructure‐guided biological effects via their inherent capacity to activate proteasome.
Self‐assembling nanomicelles constructed by small‐molecule oleanolic acid (OA) significantly activate cellular proteasome function by directly binding to 20S proteasome subunit alpha 6 (PSMA6). Mechanistically, OA nanomicelles interact with PSMA6 to dynamically modulate its N‐terminal domain conformation change, thereby controlling the entry of proteins into 20S proteasome, thus accelerating the degradation of several crucial proteins and driving cancer cell pyroptosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Protopanaxadiol (PPD), a main ginseng metabolite, exerts powerful anticancer effects against multiple types of cancer; however, its cellular targets remain elusive. Here, we synthesized a ...cell‐permeable PPD probe via introducing a bifunctional alkyne‐containing diazirine photo‐crosslinker and performed a photoaffinity labeling‐based chemoproteomic study. We identified retinoblastoma binding protein 4 (RBBP4), a chromatin remodeling factor, as an essential cellular target of PPD in HCT116 colorectal cancer cells. PPD significantly decreased RBBP4‐dependent trimethylation at lysine 27 of histone H3 (H3K27me3), a crucial epigenetic marker that correlates with histologic signs of colorectal cancer aggressiveness, and PPD inhibition of proliferation and migration of HCT116 cells was antagonized by RBBP4 RNA silencing. Collectively, our study highlights a previously undisclosed anti‐colorectal cancer cellular target of the ginseng metabolite and advances the fundamental understanding of RBBP4 functions via a chemical biology strategy.
HCT116 cells were treated with the cell permeable probe AD‐PPD, and irradiated with UV in situ. Labelled proteomes were further conjugated to biotin‐PEG3‐azide via click chemistry, and the target of protopanaxadiol (PPD) was identified as RBBP4 by LC‐MS/MS analysis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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