Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases. 

Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment

Nanozymes refer to nanomaterials that catalyze enzyme substrates into products under relevant physiological conditions following enzyme kinetics. Compared to natural enzymes, nanozymes possess the characteristics of higher stability, easier preparation, and lower cost. Importantly, nanozymes possess the magnetic, fluorescent, and electrical properties of nanomaterials, making them promising replacements for natural enzymes in industrial, biological, and medical fields. On account of the rapid development of nanozymes recently, their application potentials in regeneration medicine are gradually being explored. To highlight the achievements in the regeneration medicine field, this review summarizes the catalytic mechanism of four types of representative nanozymes. Then, the strategies to improve the biocompatibility of nanozymes are discussed. Importantly, this review covers the recent advances in nanozymes in tissue regeneration medicine including wound healing, nerve defect repair, bone regeneration, and cardiovascular disease treatment. In addition, challenges and prospects of nanozyme researches in regeneration medicine are summarized.

Nanozymes for Regenerative Medicine

Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness-controlled ceria nanocages (SRCNs) and poly(l-histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on-demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly(l-histidine) coating amount can endow the SRCNs with an ≈24-fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single-dose nanoformulation can efficaciously reduce corneal wound areas (19-fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post-administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.

Poly(l-Histidine)-Mediated On-Demand Therapeutic Delivery of Roughened Ceria Nanocages for Treatment of Chemical Eye Injury.

The growing interest in nanomedicine over the last 20 years has carved out a research field called "nanocatalytic therapy", where catalytic reactions mediated by nanomaterials are employed to intervene in disease-critical biomolecular processes. Among many kinds of catalytic/enzyme-mimetic nanomaterials investigated thus far, ceria nanoparticles stand out from others owing to their unique scavenging properties against biologically noxious free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), by exerting enzyme mimicry and non-enzymatic activities. Many efforts have been made to utilize ceria nanoparticles as self-regenerating anti-oxidative and anti-inflammatory agents for various kinds of diseases, given the detrimental effects of ROS and RNS therein that need alleviation. In this context, this review is intended to provide an overview as to what makes ceria nanoparticles merit attention in disease therapy. The introductory part describes the characteristics of ceria nanoparticles as an oxygen-deficient metal oxide. The pathophysiological roles of ROS and RNS are then presented, as well as their scavenging mechanisms by ceria nanoparticles. Representative examples of recent ceria nanoparticle-based therapeutics are summarized by categorization into organ and disease types, followed by the discussion on the remaining challenges and future research directions. This article is protected by copyright. All rights reserved.

Ceria-Based Therapeutic Antioxidants for Biomedical Applications.

Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an “independent module/cascading function” is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with “one by one” mode through a “differentiated” modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of “cascading function” in the process of disease treatment. The above engineered exosomes are used in the treatment of Parkinson's disease (PD). Moreover, the multistep targeting strategy of “disease microenvironment‐damaged cells‐diseased mitochondria” and the multistage intervention concept of “inhibiting deterioration and promoting repair” are proposed, so as to break through the bottleneck of the existing treatment of PD.

Engineered Exosomes with Independent Module/Cascading Function for Therapy of Parkinson's Disease by Multistep Targeting and Multistage Intervention Method

Gene therapy has shown great potential for neurodegenerative diseases with complex pathology. However, its therapeutic effect is limited due to the delivery barriers and its own single function. Herein, self-catalytic small interfering RNA (siRNA) nanocarriers (S/Ce-PABMS) are developed to catalyze delivery process and treatment process for synergistic treatment of neurodegenerative diseases. On the one hand, the rough surface of the S/Ce-PABMS mediated by ceria (CeO2 ) nanozymes can catalyze cellular uptake in the delivery process, so that S/Ce-PABMS with acetylcholine analogs penetrate the blood-brain barrier and enter neurons more effectively. On the other hand, the CeO2 nanozymes can catalyze the treatment process by scavenging excess reactive oxygen species, and cooperate with siRNA-targeting SNCA to decrease the α-synuclein (α-syn) aggregation and alleviate the Parkinsonian pathology. Moreover, the S/Ce-PABMS treatment reduces the number of activated microglia and regulates the release of inflammatory cytokine, thereby relieving neuroinflammation. After treatment with S/Ce-PABMS, dyskinesia in Parkinson's disease model mice is significantly alleviated. The finding shows that the self-catalytic nanocarriers, S/Ce-PABMS, have great potential in the treatment of neurodegenerative diseases.

Self-Catalytic Small Interfering RNA Nanocarriers for Synergistic Treatment of Neurodegenerative Diseases.

Nature-inspired dynamic gene-loaded nanoassemblies for the treatment of brain diseases.

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Self-Catalytic Small Interfering RNA Nanocarriers for Synergistic Treatment of Neurodegenerative Diseases.

Nature-inspired dynamic gene-loaded nanoassemblies for the treatment of brain diseases.