Journal of materials chemistry. B最新文献

Existing chemotherapeutic approaches against refractory cancers are ineffective due to off-target effects, inefficient delivery, and inadequate accumulation of anticancer drugs at the tumor site, which causes limited efficiency of drug treatment and toxicity to neighboring healthy cells. The development of nano-based drug delivery systems (DDSs) with the goal of delivering desired therapeutic doses to the diseased cells and has already proven to be a promising strategy to address these challenges. Our study focuses on achieving an efficient tumor-targeted delivery of a combination of drugs for therapeutic benefits by developing a versatile DDS by following a simple one-step chemical approach. We used low-molecular-weight chitosan and modified its primary amine groups with reactive forms of cholesterol and folic acid by simple chemical tools and thus prepared folic acid-chitosan-cholesterol graft copolymer. The polymer contains numerous residual primary amine groups, which offer enough water solubility and positive charge to its polymeric backbone to foster the interaction of negatively charged and/or hydrophobic drugs to load and encapsulate a wide variety of drugs within it via various non-bonding interactions. We used curcumin and doxorubicin as the combination of drugs and thus finally prepared targeted nanoconjugates (targeted NCs). In vitro cellular experiments show that our developed targeted NCs demonstrate 3-5 times higher cellular uptake than non-targeted NCs at various incubation times (2 h, 8 h, and 12 h) in KB cells where folate receptors are overexpressed. This enhanced cellular uptake of targeted NCs and the following delivery of drugs in the cytosol and its disposition to the nucleus exhibit a substantial amount of toxicity to KB cells towards an effective therapeutic strategy for treatment.

DNA nanostructures (DNs) have gained popularity in various biomedical applications due to their unique properties, including structural programmability, ease of synthesis and functionalization, and low cytotoxicity. Effective utilization of DNs in biomedical applications requires a fundamental understanding of their interactions with living cells and the mechanics of cellular uptake. Current knowledge primarily focuses on how the physicochemical properties of DNs, such as mass, shape, size, and surface functionalization, affect uptake efficacy. However, the role of cellular mechanics and morphology in DN uptake remains largely unexplored. In this work, we show that cells subjected to geometric constraints remodel their actin cytoskeleton, resulting in differential mechanical force generation that facilitates DN uptake. The length, number, and orientation of F-actin fibers are influenced by these constraints, leading to distinct mechanophenotypes. Overall, DN uptake is governed by F-actin forces arising from filament reorganisation under geometric constraints. These results underscore the importance of actin dynamics in the cellular uptake of DNs and suggest that leveraging geometric constraints to induce specific cell morphology adaptations could enhance the uptake of therapeutically designed DNs.

Traditional natural polysaccharide-based hydrogels, when used as drug carriers, often struggle to maintain long-term stability in the extremely harsh gastric environment. This results in unstable drug release and significant challenges in bioavailability. To address this issue, this study utilized inexpensive and safe natural polysaccharides-chitosan (CS) and high methoxyl pectin (HM)-as raw materials. Dynamic chemical bonds and anion-cation electrostatic interactions were employed to successfully prepare a super absorbent gel bead substrate (CS-HM), which serves as the "core" structure. Subsequently, another low-density hydrophilic polysaccharide, sodium carboxymethyl cellulose (CMCNa), was used to coat and crosslink the outer layer of the core, increasing the number of ionic groups. This enhancement raises the osmotic pressure inside the gel network, improving its absorption capacity. At the same time, the core-shell structure provides an energy dissipation mechanism, allowing the material to remain more stable in a strong acid environment. Due to its super absorption, high modulus, and continuous floating release properties, CS-HM@CMCNa-as a new type of acid-resistant super absorbent core-shell material-possesses the key characteristics required for gastric retention sustained-release systems. It is expected to become an ideal drug carrier for the treatment of clinical chronic diseases.

Achieving microecological balance is a complex environmental challenge. This is because the equilibrium of microecological systems necessitates both the eradication of harmful microorganisms and preservation of the beneficial ones. Conventional materials predominantly target the elimination of pathogenic microorganisms and often neglect the protection of advantageous microbial species. Metal-organic frameworks (MOFs) with excellent physicochemical properties (such as crystalline particles of various dimensions with highly porous network topology, variable local networking structures, diverse compositions with functional groups, high specific surface areas and pore volumes for surface and porous guest molecular adsorption/adhesion/affinity/binding and separation) have been extensively studied as a type of bactericidal material. However, only recently, studies on using MOFs to protect microorganisms have been reported. This review provides a comprehensive analysis of the mechanisms and applications of various MOFs (such as ZIF-8, ZIF-90, HKUST-1, MOF-5, and MIL-101) in both microbial eradication and protection. Insights into previous studies on MOF development, the material-bacteria interaction mechanisms, and potential clinical and environmental applications are also elucidated. MOFs with different framework structures/topologies (zeolite, sodalite, scaffolding, diamond, one-dimensional, and spherical/cylindrical cavities/pore networks), particle dimensions, polyhedral, cubic, rod and open/uncoordinated metal centers or fully coordinated metal centers, and ligand functional groups are discussed to understand the varying degrees of activation and interaction of microorganisms. This review holds potential in guiding future research on the design, synthesis, utilization, and integration of MOFs for the targeted eradication and protection of microorganisms and generating novel MOFs with selective antimicrobial and protective properties. Moreover, this review delivers a timely update and outlines future prospects for MOFs and their interaction with microorganisms, emphasizing their potential as a promising candidate among the next generation of smart materials in the field of ecosystem regulation.

Bioadhesive hydrogels show great promise in wound closure due to their minimally invasive nature and ease of use. However, they typically exhibit poor wet adhesion and mechanical properties on wet tissues. Herein, a ready-to-use bioadhesive hydrogel (denoted as PAA-NHS/C-CS) with rapidly robust adhesion and high mechanical strength is developed via a simple one-pot UV crosslinking polymerization of acrylic acid (AA), catechol-functionalized chitosan (C-CS), and acrylic acid N-hydroxysuccinimide ester (AA-NHS ester). Benefitting from the hydrogen bonds and electrostatic attractions formed between PAA-NHS and C-CS, the as-prepared hydrogel exhibits high tensile strength (∼630 kPa), fracture strain (∼1950%), and toughness (∼4250 kJ m^-3) in the fully swollen state. Besides, the noncovalent interactions and covalent crosslinking formed between the dual adhesive moieties (the NHS ester and catechol groups) and the tissue surface endow the hydrogel with high shear strength (∼160 kPa), interfacial toughness (∼630 J m^-2), and burst pressure (∼447 mmHg) on wet porcine skin. By integrating the high mechanical properties, rapid robust adhesion, and operational convenience, the as-prepared PAA-NHS/C-CS hydrogel shows great promise in wound closure.

While nanozymes are commonly employed in nanocatalytic therapy (NCT), the efficacy of NCT is hampered by the limited catalytic activity of nanozymes and the intricate tumor microenvironment (TME). In this work, we design a high-efficiency nanozyme with NIR-II photothermal property for the mild hyperthermia-augmented NCT. In order to endow a single-component nanomaterial the ability to simultaneously catalyze and exhibit NIR-II photothermal properties, a straightforward template method is utilized to fabricate sulfur vacancies (V_S)-doped Co₉S_8-x nanocages. Introducing V_S not only lowers the bandgap structure of Co₉S₈, enhancing its NIR-II photothermal properties, but also facilitates the control of the Co²⁺ and Co³⁺ ratio in Co₉S₈, leading to a boost in its catalytic activity. Furthermore, the catalytic efficiency of Co₉S_8-x nanocages was boosted by the mild hyperthermia. Moreover, the Co₉S_8-x nanocages exhibited high-efficiency GSH-px-mimic catalytic activity, facilitating the cascade amplification of ROS production. Through the integrated multifunctionality of Co₉S_8-x nanocages, we successfully enhanced the effectiveness of antitumor treatment with a single drug injection and a single 1064 nm laser irradiation for mild hyperthermia-augmented NCT. This work provides a distinct paradigm of endowing nanomaterials with catalytic activity and photothermal property for mild NIR-II PTT-amplified NCT through a vacancy engineering strategy.

Circulating histones have been identified as essential mediators that lead to hyperinflammation, platelet aggregation, coagulation cascade activation, endothelial cell injury, multiple organ dysfunction, and death in severe patients with sepsis, multiple trauma, COVID-19, acute liver failure, and pancreatitis. Clinical evidence suggests that plasma levels of circulating histones are positively associated with disease severity and survival in patients with such critical diseases. However, safe and efficient therapeutic strategies targeting circulating histones are lacking in current clinical practice. Extracorporeal blood purification, a widely used life support technique in intensive care units, is a promising therapeutic option for eliminating circulating histones. Inspired by electrostatic interactions between DNA chains and histones in natural nucleosomes, we propose a "one stone kills two birds" strategy to combat histone-related critical diseases by developing heparin-mimicking hydrogel microspheres (RCHMs). On one hand, the heparin-mimicking hydrogel structure inside RCHMs contains a large number of carboxyl and sulphonic acid groups by in situ cross-linking polymerization, which endows the RCHMs with excellent hemocompatibility. On the other hand, the RCHMs can adsorb circulating histones through electrostatic interactions. Our results demonstrate that the RCHMs do not cause significant hemolysis, blood cell activation and complement activation, with improved anti-protein contamination properties. The tailored RCHM microspheres (A₃M₁) can efficiently and selectively adsorb 91.16% of calf thymus histones with an adsorption capacity of 20.47 μg mg^-1 within 4 h. Moreover, the RCHMs significantly attenuate histone-mediated thrombocytopenia, platelet aggregation, and endothelial cell death. Therefore, the RCHMs are promising hemoperfusion adsorbents for extracorporeal removal of circulating histones from the blood of critically ill patients, providing a new insight into the management of multiple histone-related disorders.

Multi-organelle imaging allows the visualization of multiple organelles within a single cell, allowing monitoring of the cellular processes in real-time using various fluorescent probes that target specific organelles. However, the limited availability of fluorophores and potential spectral overlap present challenges, and many optimized designs are still in nascency. In this work, we synthesized various sulfonamide-based organic fluorophores that emit in the blue, green, and red regions to target different sub-cellular organelles. By utilizing binary mixtures, we successfully demonstrated multiple imaging of the sub-cellular organelles, such as the endoplasmic reticulum, plasma membrane, and mitochondria in HeLa cells, and dual imaging of the endoplasmic reticulum and mitochondria in A549 lung carcinoma cells with the help of blue and red-emitting fluorophores without any spectral spillover. Additionally, these photostable probes allowed precise cell staining and differentiation, structural features, and live cell dynamics. This approach of utilizing fluorescent mixtures can gain traction for various cellular studies and investigations.

This article reviews plant-derived exosome-like nanoparticles (ELNs), and highlights their potential in regenerative medicine. Various extraction techniques, including ultracentrifugation and ultrafiltration, and their impact on ELN purity and yield were discussed. Characterization methods such as microscopy and particle analysis are found to play crucial roles in defining ELN properties. This review is focused on exploring the therapeutic potential of ELNs in tissue repair, immune regulation, and antioxidant activities. Further research and optimization methods for extraction of ELNs to realize clinical potential applications are necessary.

Semiconducting polymer nanoparticles (SPNs) have been widely applied for phototheranostics. However, the disadvantage of in vivo long-term metabolism greatly suppresses the clinical application of SPNs. To improve the metabolic rate and minimize the long-term toxicity of SPNs, biodegradable semiconducting polymers (BSPs), whose backbones may be degraded under certain conditions, have been designed. This review summarizes recent advances in BSP-constructed nanoparticles (BSPNs) for phototheranostics. BSPs are divided into two categories: conjugated backbone degradable BSPs (CBD-BSPs) and non-conjugated backbone degradable BSPs (NCBD-BSPs), based on the feature of chemical structure. The biological applications, including cancer imaging and combination therapy, of these BSPNs are described. Finally, the conclusion and future perspectives of this field are discussed.