Journal of Materials Chemistry B最新文献

Targeted and efficient gene delivery systems hold tremendous potential for the improvement of cancer therapy by enabling appropriate modification of biological processes. Herein, we report the design and synthesis of a novel cationic di-block copolypeptide, incorporating homoarginine (HAG) and shikimoyl (LSA) functionalities (HDA-b-PHAG_m-b-PLSA_n), tailored for enhanced gene transfection specifically in cancer cells. The di-block copolypeptide was synthesized via sequential N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques and its physicochemical properties were characterized, including molecular weight, dispersity, secondary conformation, size, morphology, and surface charge. In contrast to the cationic poly-L-homoarginine, we observed a significantly reduced cytotoxic effect of this di-block copolypeptide due to the inclusion of the shikimoyl glyco-polypeptide block, which also added selectivity in internalizing particular cells. This di-block copolypeptide was internalized via mannose-receptor-mediated endocytosis, which was investigated by competitive receptor blocking with mannan. We evaluated the transfection efficiency of the copolypeptide in HEK 293T (noncancerous cells), MDA-MB-231 (breast cancer cells), and RAW 264.7 (dendritic cells) and compared it with commonly employed transfection agents (Lipofectamine). Our findings demonstrate that the homoarginine and shikimoyl-functionalized cationic di-block copolypeptide exhibits potent gene transfection capabilities with minimal cytotoxic effects, particularly in cancer cells, while it is ineffective for normal cells, indicative of its potential as a promising platform for cancer cell-specific gene delivery systems. To evaluate this, we delivered an artificially designed miRNA-plasmid against Hsp90 (amiR-Hsp90) which upon successful transfection depleted the Hsp90 (a chaperone protein responsible for tumour growth) level specifically in cancerous cells and enforced apoptosis. This innovative approach offers a new avenue for the development of targeted therapeutics with an improved efficacy and safety profile in cancer treatment.

As a gasotransmitter, endogenous sulfur dioxide (SO₂) plays an important role in cardiovascular regulation. In addition, excessive SO₂ can react with overexpressed hydrogen peroxide (H₂O₂) in tumor cells to generate toxic radicals, which can induce severe oxidative damage to tumor cells and result in cell apoptosis. This highlights the potential of SO₂ in oncotherapy. However, the limited availability of endogenous H₂O₂ and uncontrolled release of SO₂ gas significantly impede the effectiveness of SO₂ gas therapy. To address this challenge, a biodegradable calcium sulfite (CS) nanocarrier loaded with 10-hydroxycamptothecin (HCPT) was developed for tumor pH-triggered SO₂ gas therapy in combination with chemotherapy. This nanoreactor could be degraded in an acidic tumor microenvironment to release SO₂ gas and the HCPT drug. The released SO₂ gas induced serious oxidative damage to tumor cells by depleting glutathione (GSH) and generating toxic radicals through a reaction with intracellular H₂O₂. Simultaneously, the HCPT drug promoted tumor cell apoptosis through chemotherapy and boosted SO₂ gas therapy by elevating the H₂O₂ level within the tumor cells. Consequently, the combination of SO₂ gas therapy and chemotherapy provided a promising approach for effective tumor treatment.

Membrane-targeting compounds are of immense interest to counter complicated multi-drug resistant infections. However, the broad-spectrum effect of such compounds is often unmet due to the surges of antibiotic resistance among majority of Gram-negative bacteria compared to Gram-positive species. Though amphiphiles, synthetic mimics of antimicrobial peptides etc, have been extensively explored for their potential to perturb bacterial membranes, small molecule-based supramolecular hydrogels have remained unexplored. The design of supramolecular hydrogels can be tuned on-demand, catering to desired applications, including facile bacterial membrane perturbation. Considering the strong biocidal properties of Ag-based systems and the bacterial membrane-targeting potential of appended primary amine groups, we designed self-assembled multicomponent supramolecular Ag(I)-hydrogels with urea and DATr (3,5-diamino-1,2,4-triazole) as ligands, which are predisposed for hydrogen bonding and interacting with negatively charged bacterial membranes at physiological pH. The synthesized supramolecular Ag(I)-hydrogels exhibited almost similar antibacterial activity against both Gram-negative (Campylobacter jejuni; C. jejuni) and Gram-positive (Staphylococcus aureus; S. aureus) bacteria, with minimal inhibitory concentration (MIC) of ∼60 μg mL⁻¹. Ag(I)-hydrogels facilitated the disruption of the negatively charged bacterial membrane due to electrostatic interaction and complementary hydrogen bonding facilitated by DATr and urea. Sustained intracellular ROS generation in the presence of Ag(I)-hydrogel further expedited cell lysis. We envisage that the multicomponent supramolecular Ag(I)-hydrogels studied herein can be employed in designing effective antibacterial coatings on a range of medical devices, including surgical instruments. Moreover, the present form of the hydrogels has the potential to improve the antibacterial functionality of conventional antimicrobials, thus revitalizing the effective targeting of hard-to-treat multi-drug-resistant (MDR) bacterial infections in a clinical set up.

Skin aging is influenced by both external environmental factors and intrinsic biological mechanisms. Traditional microsphere implants aim to rejuvenate aging skin through collagen regeneration, yet their non-biodegradability and risk of granuloma formation often limit their effectiveness. In this study, we developed novel, injectable, highly bioactive, and degradable collagen–chitosan double-crosslinked composite microspheres for skin rejuvenation. The microspheres demonstrated excellent injectability, requiring an injection force of only 0.9 N, and significant biodegradability, effectively degraded in solutions containing phosphate buffer, type I collagenase, and pepsin. In addition, the microspheres exhibited excellent biocompatibility and bioactivity, significantly promoting the proliferation, adhesion, and migration of human foreskin fibroblast-1 (HFF-1) cells. In a photoaged mouse skin model, the implantation of microspheres significantly enhanced dermal density and skin elasticity while reducing transepidermal water loss. Importantly, the implant promoted the regeneration of collagen fibers. This study suggests that collagen–chitosan double-crosslinked composite microspheres hold significant potential for skin rejuvenation treatments.

Graphene oxide (GO) is a two-dimensional metastable nanomaterial. Interestingly, GO formed oxygen clusterings in addition to oxidized and graphitic phases during the low-temperature thermal annealing process, which could be further used for biomolecule bonding. By harnessing this property of GO, we created a bio-interface with patterned structures with a common laboratory hot plate that could tune cellular behavior by physical contact. Due to the regional distribution of oxygen clustering at the interface, we refer to it as patterned annealed graphene oxide (paGO). In addition, since the paGO was a heterogeneous interface and bonded biomolecules to varying degrees, arginine–glycine–aspartic acid (RGD) was modified on it and successfully regulated cellular-directed growth and migration. Finally, we investigated the FRET phenomenon of this heterogeneous interface and found that it has potential as a biosensor. The paGO interface has the advantages of easy regulation and fabrication, and the one-step thermal reduction method is suitable for biological applications. We believe that this low-temperature thermal annealing method would make GO interfaces more accessible, especially for the development of nano-interfacial modifications for biological applications, revealing its potential for biomedical applications.

Low molecular weight gels are formed via the self-assembly of small molecules into fibrous structures. In the case of hydrogels, these networks entrap large volumes of water, yielding soft materials. Such gels tend to have weak mechanical properties and a high permeability for cells, making them particularly appealing for regenerative medicine applications. Ureido-pyrimidinone (UPy) supramolecular gelators are self-assembling systems that have demonstrated excellent capabilities as biomaterials. Here, we combine UPy-gelators with another low molecular weight gelator, the functionalized dipeptide 2NapFF. We have successfully characterized these multicomponent systems on a molecular and bulk scale. The addition of 2NapFF to a crosslinked UPy hydrogel significantly increased hydrogel stiffness from 30 Pa to 1300 Pa. Small-angle X-ray scattering was used to probe the underlying structures of the systems and showed that the mixed UPy and 2NapFF systems resemble the scattering data produced by the pristine UPy systems. However, when a bifunctional UPy-crosslinker was added, the scattering was close to that of the 2NapFF only samples. The results suggest that the crosslinker significantly influences the assembly of the low molecular weight gelators. Finally, we analysed the biocompatibility of the systems using fibroblast cells and found that the cells tended to spread more effectively when the crosslinking species was incorporated. Our results emphasise the need for thorough characterisation at multiple length scales to finely control material properties, which is particularly important for developing novel biomaterials.

Similar to clinically applied thermal ablation techniques, the cellular necrosis that occurs during photothermal tumor therapy (PTT) can induce inflammatory response, severely compromising the therapeutic efficacy and clinical translation of the PTT. Inspired by the remarkable ROS-scavenging activity and high photothermal efficiency of molybdenum-based polyoxometalate (POM) and the immunostimulatory effect of cyclic dinucleotides (CDNs), a NIR-responsive and injectable DNA-mediated hybrid hydrogel (CDN–POM) has been developed. The hydrogels have superior photothermal efficiency (43.41%) to POM, impressive anti-inflammatory capability and prolonged intratumoral CDN-releasing behavior, thus enabling synergistic anti-tumor therapeutic outcomes. Meanwhile, local treatment induced by CDN–POM hydrogels displays minimal side effects on normal tissue. Taking advantage of the high phototherapeutic effect, ROS-scavenging activity and sustained CDN release of CDN–POM hydrogels, a novel combined approach that integrates photothermal therapy and immunotherapy of breast tumor is successfully pioneered.

Bacterial infections pose an increasingly serious threat to global health due to the development of drug-resistant strains. Developing a method to efficiently kill bacteria and promote tissue repair is imperative to decrease the damage from bacterial infection, especially infected wounds. Herein, a biofriendly and light-controlled nitric oxide (NO) generator HFB with simultaneous bacterial killing and wound repair properties is reported based on a tailored light-responsive molecule F(EIBC)₂. HFB demonstrates an appropriate photothermal conversion efficiency of 33.4% and type I reactive oxygen species (˙OH and H₂O₂) generation capability to simultaneously trigger NO generation and potently kill bacteria. Furthermore, HFB can effectively eradicate mature bacterial biofilms with the aid of favorable permeability of NO. Additionally, HFB effectively eradicates Staphylococcus aureus in infected wounds of living mice and accelerates healing via NO-induced angiogenesis and collagen deposition. Owing to the encapsulated human serum albumin (HSA), heavy metal-free feature, and synergistic killing mechanism, HFB exhibits good biosafety to surrounding tissue and major organs. This work provides a novel dual-functional photo-responsive molecule and a potential light-controlled release platform for the treatment of bacterial infections.

Stem cell-based therapy implementation relies heavily on advancements in cell tracking. The present research has been designed to develop a gold nanorod (AuNR) labeling protocol applied to amniotic epithelial cells (AECs) leveraging the pro-regenerative properties of this placental stem cell source which is widely used for both human and veterinary biomedical regenerative applications, although not yet exploited with tracking technologies. Ovine AECs, in native or induced mesenchymal (mAECs) phenotypes via epithelial–mesenchymal transition (EMT), served as the model. Initially, various uptake methods validated on other sources of mesenchymal stromal cells (MSCs) were assessed on mAECs before optimization for AECs. Furthermore, the protocol was implemented by adopting the biological strategy of MitoCeption to improve endocytosis. The results indicate that the most efficient, affordable, and easy protocol leading to internalization of AuNRs in living mAECs recognized the combination of the one-step uptake condition (cell in suspension), centrifugation-mediated internalization method (G-force) and MitoCeption (mitochondrial isolated from mAECs). This protocol produced labeled vital mAECs within minutes, suitable for preclinical and clinical trials. The optimized protocol has the potential to yield feasible labeled amniotic-derived cells for biomedical purposes: up to 10 million starting from a single amniotic membrane. Similar and even higher efficiency was found when the protocol was applied to ovine and human AECs, thereby demonstrating the transferability of the method to cells of different phenotypes and species-specificity, hence validating its great potential for the development of improved biomedical applications in cell-based therapy and diagnostic imaging.

Management of diseases through medication accounts for the largest portion of treatment, with people worldwide relying on a variety of medicines to treat and prevent minor to severe diseases in modern society. However, the recent increased use of counterfeit medicines rather than certified medication has emerged as a serious social concern. This study introduces a new hybrid material, named SBBF-chitosan (SC), which integrates a single-benzene-based fluorophore (SBBF) and chitosan, serving as a fluorescence-based authentication barcode for certified medication. The synthesis and characterization of SC, along with an analysis of its photophysical properties, were systematically conducted. SC demonstrated bright emission with high stability under various environmental conditions. In vitro analyses and in vivo animal experiment results further indicated the safety of SC for oral intake, even when directly incorporated into medicines. We are confident that this newly developed formulation SC provides a fundamental solution to address the challenges posed by counterfeit medicines, thereby safeguarding medication authenticity.