Journal of materials chemistry. B最新文献

This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), i.e., (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment. The physicochemical characterization revealed that 5-FU-iRGD-FA-pSL possesses optimal size, low polydispersity index, and favorable zeta potential, enhancing its stability and targeting capabilities. In vitro studies demonstrated significantly enhanced cellular uptake, cytotoxicity, and inhibition of cell migration in MCF-7 BC cells compared to free 5-FU and non-targeted liposomal formulations. DAPI staining revealed significant apoptotic features, including chromatin condensation (CC) and nuclear fragmentation (NF), with 5-FU-iRGD-FA-pSL inducing more pronounced apoptosis compared to 5-FU-pSL. Furthermore, in vivo analysis in a BC rat model showed superior anti-tumor efficacy, reduced systemic toxicity, and improved safety profile of the 5-FU-iRGD-FA-pSL formulation. This dual-targeting pSL system presents a promising approach for enhancing the therapeutic index of 5-FU, offering a potential strategy for more effective BC treatment.

Giant unilamellar vesicles (GUVs) are ideal for studying cellular mechanisms due to their cell-mimicking morphology and size. The formation, stability, and immobilization of these vesicles are crucial for drug delivery and bioimaging studies. Separately, metal-organic frameworks (MOFs) are actively researched owing to their unique and varied properties, yet little is known about the interaction between MOFs and phospholipids. This study investigates the influence of the metal-phosphate interface on the formation, size distribution, and stability of GUVs with different lipid compositions. GUVs were electroformed in the presence of a series of MOFs. The results show Al, Zn, Cu, Fe, Zr, and Ca metal centers of MOFs can coordinate to phospholipids on the surface of GUVs, leading to the formation of functional GUV@MOF constructs, with stablilities over 12 hours. Macroscopically, society has seen biology (people, plants, microbes) interacting with inorganic materials regularly. We now explore how microscopic biological models behave in the presence of inorganic constructs. This research opens new avenues for advanced biomedical applications interacting tailored frameworks with liposomes.

Development of novel Gd-based contrast agents for targeted magnetic resonance imaging (MRI) of liver cancer remains a great challenge. Herein we reported a novel Gd-based MRI contrast agent with improved relaxivity for specifically diagnosing liver cancer. This GSH-responsive macromolecular contrast agent (mCA), POLDGd, was prepared by RAFT polymerization, and its lactic acid moiety could precisely target the ASGP-R surface protein on liver cancer cells, whereas PODGd without the lactic acid moiety was prepared as a control. POLDGd had a high molecular weight of 45 kDa and a particle size of 103 nm. Its longitudinal relaxivity (11.39 mM^-1 s^-1) measured via a 3.0 T MR scanner was three times that of the clinically used contrast agent DTPA-Gd. In comparison with the PODGd-treated group, the signal enhancement at the tumor site was significantly prolonged, with a maximum enhancement peak of about 190% after intravenous injection of POLDGd into tumor-bearing mice. A high accumulation level of POLDGd in the liver tumors observed via MRI was also confirmed by fluorescence imaging. POLDGd showed minimal side effects, which may be ascribed to its metabolism through the kidneys. Therefore, POLDGd may be used as a highly effective biosafe nanoscale contrast agent for targeted MRI of liver cancer.

Piezocatalytic therapy is an emerging therapeutic strategy for eradicating drug-resistant bacteria, but suffers from insufficient piezoelectricity and catalytic active site availability. Herein, Bi-vacancies (BiV) and corona polarization were introduced to BiOBr nanosheets to create a BiOBr-BiVP nanoplatform for piezocatalytic antibacterial therapy. This meticulously tailored strategy strengthens the built-in electric field of nanosheets, enhancing piezoelectric potential and charge density and boosting charge separation and migration efficiency. Meanwhile, BiV adeptly adjust the band structure and increase reaction sites. Ultrasonication of nanosheets continuously enables the generation of reactive oxygen species (ROS) and CO, facilitating almost 100% broad-spectrum antibacterial efficacy. BiOBr-BiVP nanosheets demonstrate full bacterial eradication and accelerate wound healing through simultaneous regulation of inflammatory factors, facilitation of collagen deposition, and promotion of angiogenesis. Overall, this ultrasonic-triggered piezocatalytic nanoplatform combines BiV and the corona polarization strategy, providing a robust strategy for amplifying piezocatalytic mediated ROS/CO generation for drug-resistant bacterial eradication.

Magnesium oxide (MgO) is known for its bioactivity and osteoconductivity when incorporated into biodegradable poly(lactic acid) (PLA), whereas the weak interfacial bonding between MgO microspheres (mMPs) and PLA often leads to suboptimal composite properties with uncontrollable functionality. Conjugation of mMPs with PLA may offer a good way to enhance their compatibility. In this study, we systematically investigated two grafting techniques, solution grafting (Sol) and melt grafting (Mel), to decorate poly (D-lactic acid) (PDLA) on mMPs pre-treated by prioritized hydration to obtain Sol MPs and Mel MPs, in order to optimize the grafting efficiency and improve their controllability in the properties including the crystal structure and surface morphology. Meanwhile, the Sol method showed an improved grafting ratio (2.9 times higher) compared to the Mel method. The conjugation of mMPs with PDLA effectively neutralized the rapid pH increase during the degradation of pure mMPs, which could be used for sustainable delivery of the Mg²⁺ ions. Moreover, the Sol MPs exhibited the lowest degradation rate constant, which could be well fitted by the first-order dynamic model, suggesting a transformation of the mMP degradation mode from bulk degradation to surface degradation. This change in the biodegradation mode was beneficial for decreasing the over-basic effect caused by the quick degradation of pure mMPs, thus extending their application in the development of PDLA/MgO composites towards tissue engineering or regenerative medicine.

Total joint replacement is a successful procedure for restoring the patient's musculoskeletal mobility and quality of life, but it carries the risk of severe peri-prosthetic joint infections (PJI) and is accompanied by post-operative pain. Cocktails of multiple drugs are often used for prevention/treatment of PJI and for addressing pain. Local drug delivery systems are promising for improving the outcome of the treatment and decreasing the side effects of systemic drugs. To this end, the ultra-high molecular weight polyethylene (UHMWPE) bearing surface of the joint implant is here proposed as a platform for simultaneous release of multiple therapeutics. The combined use of non-antibiotic drugs and antibiotics, and their incorporation into UHMWPE allows to obtain novel antibacterial implant materials. The combined elution of analgesics and antibiotics from UHMWPE is found to be synergistically effective in eradicating Staphylococcus aureus, as the non-antibiotic compound significantly enhances the antibacterial activity of the antibiotic. The drug properties and the employed method for their incorporation into UHMWPE are found to dictate the morphology, thus the mechanical properties of the resulting material. By adopting various fabrication methods, novel formulations showing an enhanced antibacterial activity and outstanding mechanical properties are here proposed to amplify the functionality of polymeric implant materials.

Branched peptide-based materials draw inspiration from dendritic structures to emulate the complex architecture of native tissues, aiming to enhance the performance of biomaterials in medical applications. These innovative materials benefit from several key features: they exhibit slower degradation rates, greater stiffness, and the ability to self-assemble. These properties are crucial for maintaining the structural integrity and functionality of the materials over time. By integrating bioactive peptides and natural polymers within their branched frameworks, these materials offer modularity and tunability and can accommodate a range of mechanical properties, degradation rates, and biological functions making them suitable for biomedical applications, including drug delivery systems, wound healing scaffolds, and tissue engineering constructs. In drug delivery, these materials can be engineered to release therapeutic agents in a controlled manner, enhancing the efficacy and safety of treatments. In wound healing, they provide a supportive environment which promotes rapid and efficient tissue repair. The combination of biomimetic design and functional adaptability makes branched peptide-based materials a promising candidate for the development of next-generation biomaterials, paving the way for significant advancements in healthcare.

Combination of immunotherapy and photothermal therapy (PTT) provides a promising therapeutic performance for tumors. However, it still faces negative feedback from suppressive factors such as adenosine. Herein, we developed a new nanodrug that can combine adenosine blockade and ferroptosis to promote the photoimmunotherapy of triple negative breast cancer (TNBC). The nanodrug, named CuS-PEG@Apt, was constructed via the modification of copper sulfide (CuS) nanoparticles with adenosine aptamer and PEG. CuS-PEG@Apt could be effectively enriched in the tumor site and locally generate a strong photothermal effect, directly ablating tumors and inducing immunogenic death (ICD). On the other hand, the aptamers could block the adenosine pathway to inhibit the immune suppression by adenosine, which further promoted the anti-tumor immunity. Moreover, the CuS nanoparticles could consume GSH and inhibit GPX4 to cause the ferroptosis of tumor cells. Collectively, CuS-PEG@Apt achieved potent efficacy of tumor suppression via the combination of PTT, immune activation and ferroptosis, representing an appealing platform for TNBC treatment.

Inspired from heat shock proteins (HSPs), a thermo-sensitive coacervate-forming polycaprolactone (CPCL) was designed as a natural chaperone mimic to protect proteins from thermal stress. Unlike the coil-globule polymers of poly(N-isopropyl acrylamide) (PNIPAM), the as-designed CPCL underwent a partial dehydration during heating, characterizing it as a coacervate-forming polymer. With its ability to transform between the coil and coacervate states in response to temperature, theCPCL spontaneously captured and released targeted proteins, thereby behaving like a natural chaperone of HSPs. Remarkably, compared with the PNIPAM homopolymer, the CPCL provided more efficient protection for proteins by inhibiting heat-induced aggregation above the melting temperature (T_m). Taken together, we envision that the CPCL with excellent biodegradability and biocompatibility could be a safe excipient for protein protection against thermal damage without separation.

Supramolecular fluorescent materials with switchable behavior and induced luminescence enhancement are a new class of special materials for constructing fluorescence anti-counterfeiting materials. Since these materials are constructed by self-assembly through supramolecular host-guest interactions of non-covalent bonds, such fluorescent materials can regulate their optical properties through a reversible assembly-disassembly process. Inspired by the role of the β-barrel scaffold in activating strong fluorescence of a green fluorescent protein (GFP) chromophore, we designed a supramolecular system based on a novel GFP analogue (CA) and cucurbit[7]uril (CB[7]). CA molecules are encapsulated by CB[7] to form a 1 : 2 host-guest assembly, thereby the fluorescence brightness of CA can be tuned. The reversible regulation of fluorescence intensity was additionally realized by controlling the dynamic assembly-disassembly process in the presence of a higher binding competitor, amantadine hydrochloride. The CA-CB[7] system was successfully used for information anti-counterfeiting through the reversible fluorescence readout on A4 paper, which enables the GFP chromophore analogue and cucurbituril system to become a potential candidate for constructing intelligent information encryption and anti-counterfeiting materials.