Teng Liu

The limited loading capacity and premature leakage of conventional nanocarriers remain persistent challenges, which can be elegantly circumvented by carrier‐free supramolecular self‐assembly. To provide precise stimulus-responsive delivery of paclitaxel (PTX), we rationally designed an enzyme-responsive amphiphilic prodrug (PTX-Azo-POMs). By covalently conjugating hydrophobic PTX to hydrophilic polyoxometalates (POMs) via an azo reductase-cleavable linker, this single-entity prodrug spontaneously self-assembles into highly stable nanovesicles with a remarkably low critical aggregation concentration. When exposed to the tumor microenvironment rich in nitroso reductase, specific breakage of nitroso bonds severely disrupts the original hydrophilic hydrophobic balance, thus triggering rapid structural collapse and on-demand release of paclitaxel. In vitro studies showed that these vesicles can successfully bypass the uptake of lysosomes, promote efficient intracellular uptake of HCT116 tumor cells, and significantly enrich in the cytoplasm. Consequently, the nanovesicles exhibited significant cytotoxicity towards tumor cells, while their toxicity was significantly reduced in normal HUVEC cells. This platform ingeniously combines self-assembly without carriers with tumor-specific dynamic degradation, laying a solid theoretical and practical foundation for the intelligent nanomedicines.

The controlled self-assembly of functional molecule into supramolecular architectures with tunable properties is pivotal for advancing biomaterials. Herein, an injectable and self-healing hydrogel was formed through the synergistic co-assembly of a molybdenum polyoxometalate (Mo-POM) and guanosine monophosphate (GMP). By systematically varying the Mo-POM/GMP ratio, we achieved precise control over the hydrogel's microstructure and rheological behavior, such as its shear-thinning property, thixotropic recovery, and mechanical strength. The resulting POM@GMP hydrogel confined Mo-POM within its fibrous, three-dimensional network, which not only enhanced the photothermal agent's stability but also enabled spatially precise thermal localization. Leveraging the deep-tissue penetration of the NIR-II, the hydrogel demonstrated superior photothermal performance, which was further amplified by the tumor microenvironment through glutathione-induced activation. Cell experiments confirmed the biocompatibility of the hydrogel and its efficient, selective cancer cell ablation upon NIR-II irradiation. This work established a tunable, self-assembled platform that integrated microenvironment-responsive regulation with precision delivery, offering a promising alternative strategy for photothermal therapy by addressing the limitations of traditional agents in penetration depth, spatial control and systemic biosafety.

1. With their low toxicity, excellent selectivity to biological targets, and low adverse responses, peptide drugs—biologically active compounds made of amino acids—show a lot of promise for use in ...

Although amphiphilic PEO‐PPO block copolymers are promising drug carriers, their aggregation stability and release controllability require further optimization. In this study, a novel hyperbranched copolymer, A4, featuring 18 branching points and three aromatic rings in its core, was designed and synthesized. Compared with the conventional star‐shaped copolymer T1304, A4 exhibited a lower cloud point and larger aggregate size, demonstrating superior drug carrier properties. Beyond molecular design, a surfactant‐mediated strategy was introduced to precisely modulate the self‐assembly behavior and drug delivery performance. By incorporating cationic dodecyl trimethyl ammonium bromide (DTAB), anionic sodium dodecyl sulfate (SDS), and nonionic Tween 20, it was demonstrated that the molecular interactions between surfactants and copolymers critically govern the thermodynamic and structural properties of aggregates. Specifically, ionic surfactants embedded their hydrophobic tails into the PPO core, reducing the critical aggregation concentration and promoting the formation of larger, more stable vesicles with high drug loading capacity and sustained release profiles. In contrast, Tween 20 enhanced the hydration shell, resulting in smaller aggregates and accelerated drug release. This work elucidates the pivotal role of surfactant type in regulating the self‐assembly and drug delivery performance of PEO‐PPO copolymers, providing valuable insights for developing efficient, tunable nanocarriers to advance block copolymer applications in pharmaceutical delivery.

The controlled self-assembly of functional molecule into supramolecular architectures with tunable properties is pivotal for advancing biomaterials. Herein, an injectable and self-healing hydrogel was formed through the synergistic co-assembly of a molybdenum polyoxometalate (Mo-POM) and guanosine monophosphate (GMP). By systematically varying the Mo-POM/GMP ratio, we achieved precise control over the hydrogel's microstructure and rheological behavior, such as its shear-thinning property, thixotropic recovery, and mechanical strength. The resulting POM@GMP hydrogel confined Mo-POM within its fibrous, three-dimensional network, which not only enhanced the photothermal agent's stability but also enabled spatially precise thermal localization. Leveraging the deep-tissue penetration of the NIR-II, the hydrogel demonstrated superior photothermal performance, which was further amplified by the tumor microenvironment through glutathione-induced activation. Cell experiments confirmed the biocompatibility of the hydrogel and its efficient, selective cancer cell ablation upon NIR-II irradiation. This work established a tunable, self-assembled platform that integrated microenvironment-responsive regulation with precision delivery, offering a new paradigm for photothermal therapy by addressing the limitations of traditional agents in penetration depth, spatial control and systemic biosafety.

Bacterial infections, as a global public health problem, are a serious threat to human life and health safety with the significant increase of antibiotic‐resistant bacteria. Polyoxometalates (POMs), with their unique structure, and high biocompatibility and designability, have received widespread attention in the field of antimicrobials, showing great potential, which has led to the design of various strategies to fabricate POM‐based composites with antimicrobial properties. In this paper, the preparation strategies based on the biological components of POMs and their organic derivatives are reviewed, and the latest progress in the design and preparation of various antimicrobial POM‐based materials and the practical application of POM antibacterial materials in some fields are introduced in detail from four aspects: pure inorganic POMs, POM‐based materials bound to organic small molecules, POM‐based materials bound to organic biomolecules, and POM‐based nanocomposites. In addition, the potential antimicrobial mechanisms of POMs are summarized, and the significant advantages of POMs in collaboration with antibiotics against drug‐resistant bacteria are demonstrated. The limitations and prospects of current research are also discussed. It is hoped that this review can help researchers to keep abreast of the development of POM‐based antimicrobial materials, thus promoting their development, application, and large‐scale production.

A wide variety of polyoxometalates (POMs) have been shown to have anti-tumor activity. The hydrophobic anticancer medicine podophyllotoxin (PPT) and the hydrophilic anticancer drug POMs are combined to create the amphiphilic drug PPT-POM-PPT. PPT-POM-PPT has the ability to self-assemble into hollow vesicles. Important properties of these vesicles, such as the critical aggregation concentration, have been identified. These vesicles have low hemolytic activity and high stability. The cytotoxicity test shows that PPT-POM-PPT vesicles have strong anti-tumor activity against lung and liver cancer cells and are safe for normal cells. Cell uptake experiments confirm that PPT-POM-PPT vesicles could effectively enter tumor cells and co-locate with lysosomes. PPT-POM-PPT vesicles exhibit synergistic effects of PPT and POMs, and the vesicles can easily penetrate cell membranes and be efficiently taken up by tumor cells, thus exerting antitumor effects. PPT-POM-PPT vesicles are both the carrier and the active drug ingredient, avoiding the potential risk of introducing additional carrier ingredients and allowing efficient drug delivery. The innovative use of the anti-cancer properties of POMs and PPT to construct amphiphilic self-assembly vesicles provides a theoretical basis and a new idea for the clinical application of POMs in cancer therapy.

Tumor microenvironment‐responsive drug self‐delivery systems utilize tumor microenvironment‐responsive chemical bonds to link anti‐tumor drugs, exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self‐assembly characteristics. Upon stimulation by specific factors in the tumor microenvironment, these amphiphilic prodrug molecules can release drugs at precise sites within the tumor. These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti‐cancer drugs to normal tissues. Owing to the advanced delivery strategies such as synergistic administration and controlled drug release, tumor microenvironment‐responsive drug self‐delivery systems hold great potential for treating malignant tumors with multidrug resistance (MDR). At the same time, the stimulus‐reactivity of metal complexes provides an important opportunity to design site‐specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs. This innovative drug design complements the tumor microenvironment‐responsive self‐delivery system, providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery. This work provides a comprehensive review of recent advancements in drug self‐delivery systems, offering insights into their potential applications in cancer therapy and MDR reversal.