Journal of Materials Chemistry B最新文献

Cascading enzymatic therapy is a promising approach in cancer treatment. However, its effectiveness is often hindered by enzyme inactivation, limited exposure of active sites, cancer cell self-protection mechanisms such as autophagy, and non-specific toxicity, which can lead to treatment failure. To address these challenges, we used a low-temperature aqueous-phase synthesis method to create semi-crystalline, water-dispersible fluorescent COF nanospheres. These nanospheres can stably load glucose oxidase (GOx) and ultrafine Fe₂O₃ nanozymes, allowing for convenient coating with tumor cell membranes to form a uniform tumor-targeted cascading enzymatic nanosystem (CFGM). This system promotes a cycle of tumor glucose depletion, reactive oxygen species (ROS) generation, and oxygen production, facilitating tumor-targeted starvation therapy (ST) and chemodynamic therapy (CDT). Notably, the semi-crystalline COF carrier within this system can degrade slowly under mildly acidic conditions, forming large aggregates that damage lysosomes and disrupt lysosomal autophagy, thereby eliminating the autophagy protection of cancer cells activated by the combined ST. This synergistic approach enhances the catalytic inhibition of tumors. Our research thus provides an alternative COF-based platform and strategy for effective cancer treatment.

We report a facile technique for 3D structuring of living cells by forming capillary cell suspensions based on an aqueous two-phase system (ATPS) of polyethylene glycol (PEG) and dextran (DEX) solutions. We demonstrate the formation of water-in-water (DEX-in-PEG) capillary bridges using concentrated suspensions of yeast cells which show enhanced rheological properties and distinctive 3D patterns. Capillary structured cell suspensions can potentially find applications in novel ways of 3D cell culturing, instant tissue engineering and many biomedical investigations.

Quantification of hydroxyl radicals (˙OH), one form of reactive oxygen species (ROS), plays critical roles in early diagnosis and treatment monitoring of various diseases. In this work, we report the development of a responsive nanoprobe for ratiometric fluorescence detection and imaging of ˙OH in macrophage polarization. The nanoprobe, BSA-CCA@LDH-SRB, was designed and prepared using coumarin 3-carboxylic acid (CCA) as the sensing unit for ˙OH, and sulforhodamine B (SRB) loaded on layered double hydroxide (LDH) served as the fluorescent reference component. The coupling of CCA to bovine serum albumin (BSA) and the loading of BSA–CCA on the surface of LDH enabled the nanoprobe for fluorescence detection of ˙OH with high sensitivity and minimal interference from other biomolecules, ions, and ROS. The emission of the prepared BSA-CCA@LDH-SRB at 444 nm emerged and the intensity was increased according to the concentration of ˙OH, while the emission at 580 nm was maintained, allowing the nanoprobe for ratiometric fluorescence (F_444/580) detection of ˙OH. Loading of the BSA protein on the LDH surface and the biocompatibility and colloidal stability of the LDH-based fluorescent nanoprobe were further improved, facilitating the detection of ˙OH generation in macrophage polarization stimulated by both biomolecules and physical ultrasound irradiation. This study thus offers a new nanoprobe as the tool for investigating ˙OH evolutions, advancing the biomedical investigations of macrophage polarization associated inflammation.

The abnormal aggregation of Aβ proteins, inflammatory responses, and mitochondrial dysfunction have been reported as major targets in Alzheimer's disease (AD). Photooxygenation of the amyloid-β peptide (Aβ) is viewed as a promising therapeutic intervention for AD treatment. However, the limitations of the depth of the external light source passing through the brain and the toxic side effects on healthy tissues are two significant challenges in the photooxidation of Aβ aggregates. We proposed a method to initiate the chemical stimulation of Aβ_1–42 aggregate oxidation through H₂O₂ and correct the abnormal microenvironment of the lesions by eliminating the cascading reactions of oxidative stress. The degradable G-poly(thioacetal) undergoes cascade release of cinnamaldehyde (CA) and thioacetal triggered by endogenous H₂O₂, with CA in turn amplifying degradation by generating more H₂O₂ through mitochondrial dysfunction. A series of novel photosensitizers have been prepared and synthesized for use in the photodynamic oxidation of Aβ_1–42 aggregates under white light activation. The nanoparticles (BD-6-QM/NPs) self-assembled from BD-6-QM, bis[2,4,5-trichloro-6-(pentoxycarbonyl) phenyl] ester (CPPO), and G-poly(thioacetal) not only exhibit H₂O₂-stimulated controlled release but also can be chemically triggered by H₂O₂ to generate singlet oxygen to inhibit Aβ_1–42 aggregates, reducing the Aβ_1–42-induced neurotoxicity.

The repair of bone defects caused by osteosarcoma is still a significant clinical issue, and new scaffolds need to be developed to solve this problem. The ocean is a treasure trove for developing new biomedical materials, and coral is widely thought to be suitable as a scaffold for bone implant materials due to its porous structure and mechanical properties. Selenium is known for its antioxidant and antitumor effects, inducing tumor cell cycle arrest. In this study, we hydrothermally transformed corals to grow a hydroxyapatite layer on the scaffold surface (CHAp) and combined it with selenium to obtain selenium-doped scaffolds (Se-CHAp) without affecting the porous structure of the coral. The research successfully validates their biocompatibility and the antitumor efficacy against 143B osteosarcoma cells. The results indicate that the Se-CHAp scaffolds yielded an obvious inhibitory effect on the proliferation of osteosarcoma cells, highlighting that they have huge prospects for application in biomedical technology.

Collective behavior has become a recent topic of investigation in systems chemistry. In pursuing this phenomenon, we present polymersome stomatocytes loaded with the enzyme urease, which show basic stigmergy-based communication and are capable of signal production, reception, and response by clustering with surface complementary binding partners. The collective behavior is transient and based on the widely known pH-sensitive non-covalent interactions between nitrilotriacetic acid (NTA) and histidine (His) moieties attached to the surface of urease-loaded and empty stomacytes, respectively. Upon the addition of the substrate urea, the urease stomatocytes are able to increase the environmental pH, allowing the NTA units to interact with the surface histidines on the complementary species, triggering the formation of transient clusters. The stomatocytes display a maximum clustering interaction at a pH between 6.3 and 7.3, and interparticle repulsive behavior outside this range. This leads to oscillating behavior, as the aggregates disassemble when the pH increases due to high local urease activity. After bulk pH conditions are restored, clustering can take place again. Within the detectable region of dynamic light scattering, individual stomatocytes can aggregate to agglomerates with 10 times their volume. Understanding and designing population behavior of active colloids can facilitate the execution of cooperative tasks, which are not feasible for individual colloids.

Magnetic-fluorescent microbeads have been widely used in the multiplex detection of biological molecules. The traditional method relies on flow cytometry to decode and analyze the microbeads. Alternative strategies that employ immobilized microbeads on a plane and involve fluorescence imaging to analyze the microbeads have been proposed. Among these strategies, an integrated chip that controls magnetic field contribution using nickel powder pillars and captured microbeads has attracted great attention. Despite its unique advantages such as low manufacturing costs, reusability and high capture efficiency, existing research had been limited by the inability to precisely capture a single microbead, and the overlapping of microbeads has made multiplex immunoassays based on this strategy impossible. In this work, low-density microbeads were prepared in a microfluidic chip using IBOMA as the main monomer. The low density of the microbeads made the preparation of an aqueous suspension easier. An integration of nickel patterns, magnets and channels was carried out and demonstrated the capacity of capturing single microbeads precisely. Fluorescence coding further empowered this method with the ability of multiplex immunoassay, which was verified using three types of IgG, and a calibration curve for the detection of anti-human IgG was established using a sandwich immunoassay. These results show the promising potential of this strategy for biomedical detection.

Prophylactic human papillomavirus (HPV) vaccines against cervical cancer were successfully developed; however, challenges such as high cost and low compliance still remain to be overcome. In addition, because many HPV types can cause cervical cancer, antigens of multiple HPV types are needed to achieve broad protection. In this study, a bivalent single-injection HPV vaccine was designed in which virus-like particles (VLPs) of HPV 16 L1 and HPV 18 L1 were used as antigens. A recently developed drug carrier that uses tannic acid/polyethylene glycol films as the erodible layer was employed to accomplish multiple pulsatile releases of the antigens. Monovalent single-injection vaccines for HPV 16 and HPV 18 were first designed. A bivalent single-injection vaccine was then obtained by simply mixing the two monovalent vaccines. The bivalent vaccine provided protection against both HPV types. More importantly, it elicited both humoral and cellular immune responses as potent as those elicited by the corresponding multiple dose vaccine because of their similar release profile of antigens. Cross-reactivity was observed between HPV 16 and 18 in terms of cellular immune responses, while no cross-reactivity was found in terms of humoral immune responses. Note that other multivalent single-injection vaccines could be designed in the same way. These vaccines are expected to help prevent cervical cancer because of their broad protection, enhanced compliance and lowered vaccination cost.

A cation channel possessing cascaded hydrated acid groups has been successfully constructed using pillar[5]arene integrated with dual cyclodextrins. As a proof-of-concept, the secondary side of cyclodextrin substituted by 24 –CO₂H groups presents high coordination sites, which helps hydrated cations to quickly dehydrate and accelerates efficient cation transport (Rb⁺ > Cs⁺ > K⁺ > Na⁺ > Li⁺). Notably, benefitted by the protonation and deprotonation of –CO₂H groups, ion permeation activity of the channel molecules under acidic condition (pH = 6.0) is 2.8 times higher than that under alkaline conditions (pH = 8.0), exhibiting pH-modulated property and promising potential in building intelligent artificial ion channels with customized features.

In this work, a series of cationic luminogens (designated as PSMP isomers) were developed based on the cyano positional isomerism strategy. The isomerism of the cyano substituent on the molecular skeleton can finely regulate the optical behaviour, the type of photoinduced reactive oxygen species (ROS), and mitochondria-targeted capability of isomers. Interestingly, PSMP-4, with the cyano group installed at an appropriate location, exhibits a special aggregation-induced emission effect and potent O₂˙⁻ generation efficacy through the type I photochemistry pathway. Notably, PSMP-4 can accumulate in mitochondria with high specificity. Taking advantage of its excellent photostability, PSMP-4 realizes in situ mitochondria imaging in a washing-free manner and sensitive response to the change of mitochondrial membrane potential. The integration of comprehensive photophysical properties and mitochondrial specificity enable PSMP-4 to successfully trigger the death of cancer cells through an efficient type I photodynamic therapy process both in vitro and in multicellular tumor spheroid models.