Small Science最新文献

Piezoelectric nanomaterials are highly promising for remote cell stimulation due to their ability to convert mechanical energy, such as ultrasound (US), into electrical cues that modulate cellular behavior. In the context of cancer treatment, piezoelectric stimulation has recently shown antiproliferative, chemosensitizing, antiangiogenic, and immunomodulatory effects. Despite growing interest in organic alternatives, no biodegradable or bioabsorbable nanoparticles with clinically approved components have yet been developed with piezoelectric properties for cell stimulation, limiting the translational potential of this approach. Here, chitosan nanoparticles (ChNPs) have been engineered to exhibit intrinsic piezoelectric properties, enabling US-mediated activation. Their structural, mechanical, and piezoelectric characteristics have been investigated using advanced physicochemical and electromechanical techniques. Biological evaluation of US-driven ChNPs-assisted piezostimulation has been tested on patient-derived glioblastoma cells. When stimulated with US, ChNPs demonstrate not only excellent antiproliferative activity, but also proapoptotic efficacy, even in the absence of any chemotherapeutic agent. This drug-free anticancer stimulation approach is attributed to reactive oxygen species generation triggered by the ChNP piezocatalytic properties. The antitumor activity is further validated in more complex ex ovo models. The combination of piezoelectric responsiveness, biodegradability, and preclinical feasibility highlights the potential of ChNPs as a safe, noninvasive therapeutic platform for next-generation cancer treatments.

With the ageing of the global population, cartilage-related diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IVDD), have increasingly become significant social problems threatening human health. Therefore, targeted therapy for cartilage is becoming more and more promising. Exosomes, natural cellular derivatives, have emerged as promising therapeutic vectors owing to their inherent biocompatibility, superior biomatrix penetration capabilities, and therapeutic efficacy in cartilage regeneration. Precise targeting of cartilage tissues can be achieved through specific construction strategies, showing potential for treating cartilage-related diseases. However, a review of cartilage-targeted exosomes is still lacking. Previous studies have merely categorized chondrocytes under the broader group of osteocytes, regarding them only as a supplementary component of bone-targeted therapy, or have been limited to a single modification technique. This review specifically focus on cartilage-targeted exosomes, systematically integrating two modification methods-direct surface modification and parental cell engineering-and highlights translational applications in disease contexts. This article elaborates in detail on the construction strategies of cartilage-targeted exosomes and explores their application progress in related diseases such as OA and IVDD, aiming to provide a reference for further research and clinical translation in this field.

The uncontrolled pharmacokinetics of anticancer drugs after systemic administration can cause off-target accumulation in healthy tissues, compromising the antitumor efficacy and posing serious safety issues. To address these limitations, the spatiotemporally controlled inverse electron demand Diels-Alder reaction (SC-IEDDA) strategy is developed, which controls bioorthogonal IEDDA reactions within tumor tissues for in situ prodrug activation and precise chemotherapy. The strategy employs two nanoplatforms: 1) pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles encapsulating trans-cyclooctene-caged doxorubicin (TCO-DOX, the prodrug) and 2) indocyanine green (ICG)-loaded near-infrared (NIR) light-responsive nanomicelles constructed from an amphiphilic molecule comprising the tetrazine (Tz) moiety conjugated to polyethylene glycol via a thioketal (TK) linker. During systemic circulation, both nanoplatforms remain intact to prevent premature prodrug activation. Following tumor accumulation via the enhanced permeability and retention effect, the acidic environment triggers ZIF-8 degradation, locally releasing TCO-DOX. Simultaneously, NIR laser irradiation induces ICG's production of reactive oxygen species, cleaving the TK linker to liberate the Tz activator. This enables the precise triggering of bioorthogonal IEDDA reaction between TCO-DOX and Tz at the tumor site, ensuring the uncaging of doxorubicin to exert efficient antitumor efficacy. This strategy represents a critical advancement in the safe and effective application in precision oncology.

Regulatory T cells (Tregs) orchestrate immune tolerance, protecting against autoimmunity and promoting transplant tolerance, yet they can also facilitate tumor immune evasion. Advances in nanotechnology now permit high-precision manipulation of Treg biology. Tailored polymeric, lipid-based, inorganic, and biomimetic nanoparticles can be engineered to deliver antigens, cytokines, small-molecule drugs, antibodies, or nucleic acids that selectively expand or stabilize Tregs for tolerogenic therapy; the same design principles can be inverted to inhibit or deplete intratumoral Tregs, thereby restoring effective antitumor immunity. Beyond intentional therapies, the review also explores unintended immunological consequences of nanoparticles, such as inadvertent induction of Tregs or broader immunosuppressive responses, and how Tregs can conversely limit the efficacy of nanoparticle-based vaccines or cancer nanotherapies. Outstanding challenges related to targeting efficiency, safety, manufacturability, and combinatorial therapeutic strategies are outlined, and prospective avenues for future investigation are highlighted. Collectively, emerging data position Treg-focused nanomedicine as a versatile and clinically relevant toolkit for restoring or unleashing immunity across autoimmunity, transplantation, and oncology.

Diabetic skin lesions, as one of the most common complications of diabetes, present chronic nonhealing wounds that face dual challenges of antibiotic-resistant bacteria threat and insufficient microenvironment regulation due to hyperglycemic conditions, bacterial infections, and multiple pathological factors (e.g., hypoxia and reactive oxygen species (ROS) accumulation and growth factor deficiency). This study develops a microneedle (MN) system integrated with copper nanocluster-decorated magnesium silicate nanoparticles (denoted as MS@Cu MNs), which enables efficient diabetic wound healing via a synergistic multimechanism strategy. Leveraging the unique enzyme-mimetic activity of copper nanoclusters (CuNCs) and the angiogenic properties of magnesium silicate nanoparticles (MS NPs), the engineered MS@Cu nanocomposites demonstrate: 1) broad-spectrum antibacterial efficacy (sterilization rate >99.9%), 2) microenvironment regulation via simultaneous hypoxia mitigation, ROS scavenging, and angiogenesis promotion, and 3) enhanced fibroblast proliferation and migration through PI3K-AKT signaling pathway activation. The MN system using γ-polyglutamic acid (γPGA) as a matrix exhibits both superior mechanical strength and excellent biodegradability. In vivo studies demonstrated accelerated closure of infected diabetic wounds in animal models, with histological analysis revealing robust mature collagen deposition and tissue regeneration. This study develops an integrated strategy for chronic diabetic wound management, combining potentiated antibacterial activity with targeted microenvironment remodeling.

Lithium-sulfur batteries (LSBs) is fundamentally limited by the "shuttle effect" and poor kinetics. To address these challenges, this study proposes an approach through developing a novel organic polysulfide composite cathode with high sulfur loading. By implementing a radical reaction between elemental sulfur and a disulfide of tetramethylthiuram disulfide (TMTD), linear organic polysulfides (TMTD-S) containing over 70 wt% sulfur are successfully synthesized. This kind of material features a covalently bonded R-Sn-R (R=C₂H₆N(S)) backbone. Further compounding with the conductive carbon (ECP600JD) and integrating into a paper-based electrode help to improve the electrode's conductivity and optimized ion transport pathways. The obtained TMTD-24S@ECP600JD cathode demonstrates a capacity retention rate of 79.1% after 250 cycles at 0.2C, far superior to traditional S@ECP600JD materials (14.1%). By increasing the sulfur content in TMTD, higher sulfur-content linear organic polysulfides are also obtained. Among them, the TMTD-54S@ECP600JD with 88 wt% sulfur content exhibits the best electrochemical performance and the highest lithium-ion diffusion coefficient, delivering an initial discharge capacity of 941 mAh g^-1 at 0.2C, with a capacity retention rate of 82.1% after 200 cycles. Even at a high rate of 2C, it still maintained a high specific capacity of 638.3 mAh g^-1, making it a potential material for high-performance Li-S batteries.

This study presents a comprehensive investigation on the relationship between structure, synthesis parameters, and porous properties of sol-gel-derived polymer gels. The formation of the porous gels is monitored with in situ small-angle X-ray scattering, in situ nuclear magnetic resonance spectroscopy (NMR), and NMR cryoporometry. The transition of the reaction solution to a solid gel is governed by the consumption of the phenolic monomer. Primary particle growth and nanopore formation proceed during this short time period and are completed when all resorcinol is consumed. The kinetics of these processes are temperature-dependent and they are completed within 12 min at 120 °C and within 60 min at 80 °C. Extending the reaction time further results in enhanced cross-linking of the polymer, as observed by solid-state ¹³C NMR spectroscopy. Extended reaction time, i.e., higher degree of polymer cross-linking, enhances pore stability and reduces gel shrinkage during drying, resulting in xerogels with larger pore volume, larger external surface area, and larger average pore sizes. This work rationalizes molecular-scale transformation of polymers with macroscopic properties, thus providing a rational tool for tuning aerogel/xerogel performance through synthesis design.

With the advancement of hydrogel technology, increasing attention has been drawn to hydrogel microspheres (HMs) due to their versatile biomedical applications. HMs play pivotal roles in biomedical applications, such as drug delivery, cell culture, regenerative medicine, wound healing, and tumor immunity. Composed of diverse biobased materials and fabricated through various preparation methods, HMs offer unique structural and functional advantages. This review focuses on the latest findings to provide a more comprehensive understanding of HMs for biomedical applications. Their therapeutic potential across multiple disease contexts is highlighted, and emerging trends and challenges are discussed. By consolidating current knowledge, this work aims to inspire further research and accelerate the clinical translation of HMs.

Infected diabetic foot ulcer (DFU) endangers patients through complex complications, which seriously increase the risk of amputation, prolongation of disability time and mortality, as well as bring a heavy burden to the medical system. This review focuses on the emerging biomedical engineering therapy of DFU and deeply analyzes the multiple pathogenic factors driving these intractable DFU wounds, including impaired angiogenesis, inflammatory disorder, microbial biofilm formation, and impaired immune response. It also synthesizes current clinical treatments and elaborates on their limitations that underscore the need for innovative solutions. The core of the review delves into recent breakthroughs in responsive antimicrobial biomaterials, emphasizing their stimuli-triggered mechanisms that enable targeted drug release, enhanced bacterial eradication, and tissue regeneration promotion. Furthermore, it explores future trajectories for multifunctional biomaterials, envisioning integrated systems that combine antimicrobial, anti-inflammatory, and pro-healing properties to address the complex pathophysiology of infected DFU. By bridging current clinical challenges with biomaterial innovations, it can provide actionable insights for developing patient-centric therapeutic strategies in biomedical engineering.

A photomagnet, Co₈[W(CN)₈]₅Cl·(pyrazine)₁₁·21H₂O, exhibiting Class II mixed valency due to homometallic intervalence charge transfer (IVCT) between Co^II and Co^III centers, is synthesized. The compound features a 3D cyanido-bridged CoW coordination network composed of two crystallographically independent Co sites (Co1 and Co2) and one W site. Rectangular tubular structures formed by Co1-W bridges are further crosslinked by the Co2 sites. Defects in the [W(CN)₈] sites enable the formation of pyrazine bridges between the Co1 sites. Upon cooling, the compound undergoes a two-step thermal phase transition, attributed to heterometallic charge-transfer-induced spin transitions between high- and low-spin electronic states. The first-step charge transfer (CT) phase transition leads to the formation of homometallic [Co^II-pyrazine-Co^III] bridges, producing a near-infrared IVCT band at 2300 nm. Photoirradiation at 785 nm at 3 K induces a transition to a photoinduced (PI1) phase. The PI1 phase also shows a homometallic IVCT band due to the emergence of the [Co^II-pyrazine-Co^III] state. Subsequent photoirradiation at 532 nm to the PI1 phase induces a transition to the paramagnetic photoinduced (PI2) phase. This study demonstrates the modulation of electronic states in a phase transition material and a photomagnet, enabled by homo- and heterometallic CT processes.