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a–e) SEM and f–j) STEM/EDX images of synthesized MSNs: a,f) unfunctionalized MSNs (un‐MSNs), b,g) R1‐SCH3‐A, c,h) R2‐SCH3‐A, d,i) R3‐SCH3‐A, and e,j) R4‐SCH3‐A.
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Mesoporous silica nanoparticles (MSNs) with reactive oxygen species (ROS)‐responsive “nanogate” as drug delivery platforms are extensively investigated for biomedical applications. However, the physical blockages used to control the cargo release are often limited by their poor sealing ability and low biocompatibility. Herein, a design of free‐bloc...
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... Cerium oxide nanoparticles (ceria) have a long history of being tested for the potential clinical efficacy of both wet and dry forms of AMD because they have the inherent ability to auto-renew and target oxidative stress [11][12][13][14][15]. However, the antioxidative activity of ceria has been greatly hampered by its poor water colloidal stability, which may not be enough to prevent oxidative damage, given the potential clinical implementation in diseases. ...
Excessive production of reactive oxygen and nitrogen species (RONS) leads to nonspecific inflammation and is a major cause of the pathogenesis of exudative and nonexudative forms of age-related macular degeneration (AMD). As a result, antioxidant therapy has been emerging as a promising means for the treatment and prevention of AMD. Nevertheless, antioxidant strategies have largely been unsuccessful for AMD treatment. Developing a more potent antioxidant that reaches its target, remains stable with specific RONS level regulation, and reduces treatment burdens would provide a foundation for the care and scientific understanding of using antioxidant therapies in AMD. To overcome these limitations, we developed a novel robust nanotechnology-mediated antioxidant strategy based on ceria-coated melanin-PEG nanoparticles (CMNPs) by taking advantage of their inherent antioxidant ability to autorenew cerium oxide nanoparticles (ceria) and their photoprotective role through scavenging a broad range of RONS of melanin. Our experiments demonstrate that CMNPs could relieve AMD-like pathology with long-term improvement and exhibited a significant synergistic effect in scavenging against multiple RONS compared to single-nanoantioxidant delivery. More importantly, CMNPs ensured autoregenerative properties, outperformed aflibercept, and relieved pathological damage in an AMD-like mouse model through a single-dose administration for up to three months. This study highlights a novel treatment targeted to preserve the RPE and photoreceptors in AMD as a monotherapy.
... This observed change can be due to the formation of hydrogen bonds between the silanol and carboxyl groups of IND. It has been reported that the silanol groups present on the surface of the MSNs provide an active site for molecular drug interactions [55][56][57]. ...
Mesoporous silica nanoparticles (MSNs) have shown incredible potential for drug delivery owing to their orderly mesoporous structure, high surface area, pore volume, and biocompatibility. pH-responsive MSN-based drug delivery systems may be used to deliver anticancer agents. This manuscript reports MSNs exclusively for pH-based drug delivery for controlled delivery applications. This study reports the development of positively charged MSNs under acidic conditions using a “modified sol–gel method.” The developed MSNs were loaded with doxorubicin, a positively charged anticancer drug, lidocaine, a neutral topical anesthetic, and indomethacin, a negatively charged anti-inflammatory drug, by adsorption method. ATR-FT-IR spectra and XRD patterns of the neat MSNs and drug-loaded MSNs were obtained to study their physicochemical nature. SEM and TEM images showed the hexagonal arrangement of the neat MSNs and the changes observed after drug loading. The pH-responsive behavior of the MSNs loaded with the drugs was also characterized. From the results, we observed that the MSNs could be triggered to release the drugs by the pH of the solution and, therefore, could be a potential candidate for pH-based drug delivery systems. In vitro cytotoxicity assays were performed to study the anticancer activity of DOX-loaded MSNs. These in vitro studies were performed using three cancer cell lines, viz., MG-63 osteosarcoma cells, MCF-7 breast cancer cells, and MDA-MB-231 breast cancer cells. These assays showed effective inhibitory activity of the DOX-loaded MSNs. Furthermore, we have applied mathematical modeling to investigate the release of DOX from the pH-responsive MSNs in different pH environments. From the obtained modeling results, the sustained release of DOX from the non-functionalized MSNs fits well with the saturation kinetics model. Therefore, these positively charged MSNs synthesized by the modified sol–gel method can be potentially used for cancer therapy.Graphical Abstract
... For example, metformin (MET) was loaded on MSN, which provided the possibility for long-term ROS-scavenging activity to achieve the antioxidative effect [12]. Methylthio-functional MSN was prepared to regulate amounts of ROS by the oxidation of methylthiopropyl groups to sulfoxides in response to the presence of H 2 O 2 [13]. Two antioxidant enzymes were simultaneously delivered by functional MSNs, which revealed synergistic efficiency of ROS scavenging [14]. ...
... One organic silicon source of organosilica precursor Trp-Met-Si was first designed and synthesized by using Trp-Met dipeptide as the main reactant via a multiple-step method, as shown in Scheme 1I. The molecule Trp-Met-Si was confirmed by 1 H NMR, 13 The wide-angle X-ray diffraction (XRD) patterns of mesoporous organosilica Trp-Met-x-PMO are shown in Figure 2. All the materials exhibited a high intensity peak from the (100) plane in the range of 2θ from 1 • to 7 • . Moreover, the intensity of the diffraction peak varied with the changing amounts of dipeptide Trp-Met in the skeleton of the mesoporous organosilica material. ...
... The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ma16020638/s1, Figure S1: 1 H NMR of organosilica precursor Trp-Met-Si; Figure S2: 13 ...
A nanoantioxidant of mesoporous organosilica (Trp-Met-PMO) based on the framework of tryptophan–methionine dipeptide was first designed and constructed by condensation between self-created dipeptide organosilica precursor (Trp-Met-Si) and tetraethyl orthosilicate (TEOS) in alkaline conditions under the template hexadecyl trimethyl ammonium bromide (CTAB). Trp-Met-Si was prepared by the reaction between dipeptide Trp-Met and conventional organosilicon coupling agent isocyanatopropyltriethoxysilane (IPTES) via a multiple-step reaction method. The material Trp-Met-PMO was confirmed by XRD, FT-IR and N2 adsorption–desorption analysis. The material Trp-Met-5-PMO with low amounts of organosilica precursor remained a mesoporous material with well-ordered 2D hexagonal (P6mm) structure. With increasing amounts of organosilica precursor, a mesoporous structure was still formed, as shown in the material Trp-Met-100-PMO with the highest amounts of organosilica precursor. Moreover, pore size distribution, surface area and porosity of Trp-Met-PMO are regulated with different amounts of organosilica precursor Trp-Met-Si. The antioxidant activity of Trp-Met-PMO was evaluated by ABTS free radical-scavenging assay. The results showed that antioxidant activity was largely enhanced with increasing contents of organosilica precusor Trp-Met-Si in the skeleton. The material Trp-Met-40-PMO exhibited maximum scavenging capacity of ABTS free radicals, the inhibition percent was 5.88%. This study provides a design strategy for nanoantioxidant by immobilizing short peptides within the porous framework of mesoporous material.
Significant health risks are posed by meningitis due to its rapid progression, and challenges are encountered in intravenous antibiotic administration, especially in crossing the blood‐brain barrier. To address this, an inflammation‐activated, endogenous macrophage (MΦ)‐mediated oral prodrug delivery system is developed for targeted therapeutic interventions in bacterial meningitis treatment. This system is guided by inflammation‐derived chemoattractants and triggers drug release through inflammation‐induced reactive oxygen species (ROS). Comprised of naturally derived β‐glucans conjugated with the antibiotic cefotaxime (CTX) using a ROS‐responsive linker, nanoparticles (βGlus–CTX NPs) are formed in aqueous solutions. In a mouse model of Klebsiella pneumoniae‐induced meningitis, orally administered βGlus–CTX NPs are traversed by intestinal microfold cells, surpassing the intestine‐epithelial barrier, and are absorbed by resident endogenous MΦ. These MΦ‐mediated drug delivery vehicles are then traveled through the lymphatic and circulatory systems, crossing the compromised blood‐brain barrier, ultimately reaching inflamed brain tissues, guided by their derived chemoattractants. In ROS‐rich inflamed tissue environments, the linkers in the βGlus–CTX NPs are cleaved, releasing therapeutic CTX for localized treatment. Targeted antibiotic treatment for bacterial meningitis is offered by this oral, endogenous MΦ‐mediated prodrug delivery system, overcoming the robust gut‐to‐brain biological barriers and potentially enhancing effectiveness for comfortable home‐based treatment.
Targeted drug delivery system (DDS) holds exciting prospects in biomedical clinical research and drug development. However, it faces a significant challenge in achieving stable and safe targeted transportation without drug leakage while obtaining precise and controllable drug dosing with a high drug utilization rate and low side effects. Herein, an optical tweezers‐based light‐driven technique is proposed to transport and construct multi‐core/shell microdroplets enveloping drug carriers and target cells as a novel, safe, and efficient targeted DDS. Drug‐loaded microdroplets with core/shell structures are first fabricated by a new and simple injection extrusion method and then it is transported to a target cell by a dynamic optical trap with a low optical power, which ensures no drug leakage, exogenous materials, and biothermal damage are introduced during the drug delivery process. Next, precise drug dosing is realized by pushing the target cell into the drug‐loaded microdroplet under the actions of optical forces, which constructs a multi‐core/shell microdroplet structure with a pure drug environment to improve the drug action efficiency. Moreover, quantitative drug dosing with a high drug utilization rate can also achieved by controlling the sizes/number of drug droplets inside the microdroplets. This light‐driven DDS is of great interest to frontier medical research and disease treatment fields.
A novel ionized heavy-atom-free two-dimensional organic nanosheet was prepared and exhibited highly selective generation of singlet oxygen under both light and ultrasound excitation. These ionized nanosheets displayed excellent dispersibility in...
The invention of silica-based bioactive glass in the late 1960s has sparked significant interest in exploring a wide range of silicon-containing biomaterials from the macroscale to the nanoscale. Over the past few decades, these biomaterials have been extensively explored for their potential in diverse biomedical applications, considering their remarkable bioactivity, excellent biocompatibility, facile surface functionalization, controllable synthesis, etc. However, to expedite the clinical translation and the unexpected utilization of silicon-composed nanomedicine and biomaterials, it is highly desirable to achieve a thorough comprehension of their characteristics and biological effects from an overall perspective. In this review, we provide a comprehensive discussion on the state-of-the-art progress of silicon-composed biomaterials, including their classification, characteristics, fabrication methods, and versatile biomedical applications. Additionally, we highlight the multi-dimensional design of both pure and hybrid silicon-composed nanomedicine and biomaterials and their intrinsic biological effects and interactions with biological systems. Their extensive biomedical applications span from drug delivery and bioimaging to therapeutic interventions and regenerative medicine, showcasing the significance of their rational design and fabrication to meet specific requirements and optimize their theranostic performance. Additionally, we offer insights into the future prospects and potential challenges regarding silicon-composed nanomedicine and biomaterials. By shedding light on these exciting research advances, we aspire to foster further progress in the biomedical field and drive the development of innovative silicon-composed nanomedicine and biomaterials with transformative applications in biomedicine.
Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, and excellent biocompatibility. Over the past two decades, researchers have developed a wide variety of MSNs-based nanoplatforms through careful design and controlled preparation techniques, demonstrating their adaptability to various biomedical application scenarios. With the continuous breakthroughs of MSNs in the fields of biosensing, disease diagnosis and treatment, tissue engineering, etc., MSNs are gradually moving from basic research to clinical trials. In this review, we provide a detailed summary of MSNs in the biomedical field, beginning with a comprehensive overview of their development history. We then discuss the types of MSNs-based nanostructured architectures, as well as the classification of MSNs-based nanocomposites according to the elements existed in various inorganic functional components. Subsequently, we summarize the primary purposes of surface-functionalized modifications of MSNs. In the following, we discuss the biomedical applications of MSNs, and highlight the MSNs-based targeted therapeutic modalities currently developed. Given the importance of clinical translation, we also summarize the progress of MSNs in clinical trials. Finally, we take a perspective on the future direction and remaining challenges of MSNs in the biomedical field.
Using inefficient pesticides that target pests can elevate the risk of pesticide residues, which leads to significant threats to the safety both of human food and non-target organisms. Delivery systems...
