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Inflammatory bowel disease (IBD) is a chronic inflammatory disease with limited therapeutic outcomes. Macrophages are the key gatekeepers of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages are recognized as attractive targets to develop new therapeutic. However, the therapy development has proven challenging due to the malignant biological chain between macrophage immune hyperresponsiveness and dysbiosis of intestinal microflora. Herein, a carrier‐free nano‐drug, PCNPs@PEG‐Man, with dual‐targeting function, is produced due to IBD lesion‐specific positive charge and high expression of mannose receptor. With super resistance against extreme intraluminal conditions, PCNPs@PEG‐Man showes stable ROS‐scavenging properties thereby. Notably, the dual‐targeting strategy enhances the endocytosis efficiency and intestinal retention time of the drug, which is conducive to the downregulation of pro‐inflammatory factors, upregulation of anti‐inflammatory factors, and repair of the intestinal barrier. Additionally, it reshaped the dysbiosis of intestinal bacteria, revealing an optimized gut flora composition of probiotics. The mechanism of the carrier‐free nano‐drug mainly involves the elimination of oxidative stress, promoting macrophage M2 polarization, and restoring gut homeostasis. The synergistic effect inherent in this dual‐targeting system presents an effective and safe approach to managing IBD, providing new insights into the treatment of intestinal ROS‐mediated diseases associated with microbiota dysbiosis. This manuscript presents a carrier‐free nanomedicine PCNPs@PEG‐Man with dual‐targeting for IBD. It resists harsh intestinal conditions, reduces oxidative stress, enhances drug uptake and retention, modulates inflammation, and reshapes gut microbiota, offering a safe and effective IBD therapy.

Despite the many advancements in the pharmaceutical and medical fields and the development of numerous antimicrobial drugs aimed to suppress and destroy pathogenic microorganisms, infectious diseases still represent a major health threat affecting millions of lives daily. In addition to the limitations of antimicrobial drugs associated with low transportation rate, water solubility, oral bioavailability and stability, inefficient drug targeting, considerable toxicity, and limited patient compliance, the major cause for their inefficiency is the antimicrobial resistance of microorganisms. In this context, the risk of a pre-antibiotic era is a real possibility. For this reason, the research focus has shifted toward the discovery and development of novel and alternative antimicrobial agents that could overcome the challenges associated with conventional drugs. Nanotechnology is a possible alternative, as there is significant evidence of the broad-spectrum antimicrobial activity of nanomaterials and nanoparticles in particular. Moreover, owing to their considerable advantages regarding their efficient cargo dissolving, entrapment, encapsulation, or surface attachment, the possibility of forming antimicrobial groups for specific targeting and destruction, biocompatibility and biodegradability, low toxicity, and synergistic therapy, polymeric nanoparticles have received considerable attention as potential antimicrobial drug delivery agents. In this context, the aim of this paper is to provide an up-to-date overview of the most recent studies investigating polymeric nanoparticles designed for antimicrobial therapies, describing both their targeting strategies and their effects.

RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases. The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted the medical value of RNA drugs. However, one of the major challenges in realizing the full potential of RNA drugs is to deliver RNA into specific organs and tissues in a targeted manner, which is crucial for achieving therapeutic efficacy, reducing side effects, and enhancing overall treatment efficacy. Numerous attempts have been made to pursue targeting, nonetheless, the lack of clear guideline and commonality elucidation has hindered the clinical translation of RNA drugs. In this review, we outline the mechanisms of action for targeted RNA delivery systems and summarize four key factors that influence the targeting delivery of RNA drugs. These factors include the category of vector materials, chemical structures of vectors, administration routes, and physicochemical properties of RNA vectors, and they all notably contribute to specific organ/tissue tropism. Furthermore, we provide an overview of the main RNA-based drugs that are currently in clinical trials, highlighting their design strategies and tissue tropism applications. This review will aid to understand the principles and mechanisms of targeted delivery systems, accelerating the development of future RNA drugs for different diseases.RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases. The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted the medical value of RNA drugs. However, one of the major challenges in realizing the full potential of RNA drugs is to deliver RNA into specific organs and tissues in a targeted manner, which is crucial for achieving therapeutic efficacy, reducing side effects, and enhancing overall treatment efficacy. Numerous attempts have been made to pursue targeting, nonetheless, the lack of clear guideline and commonality elucidation has hindered the clinical translation of RNA drugs. In this review, we outline the mechanisms of action for targeted RNA delivery systems and summarize four key factors that influence the targeting delivery of RNA drugs. These factors include the category of vector materials, chemical structures of vectors, administration routes, and physicochemical properties of RNA vectors, and they all notably contribute to specific organ/tissue tropism. Furthermore, we provide an overview of the main RNA-based drugs that are currently in clinical trials, highlighting their design strategies and tissue tropism applications. This review will aid to understand the principles and mechanisms of targeted delivery systems, accelerating the development of future RNA drugs for different diseases.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

The tumor microenvironment (TME) is being increasingly recognized as a key factor in multiple stages of disease progression, particularly local resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. An appropriate understanding of the TME promotes evaluation and selection of candidate agents to control malignancies at both the primary sites as well as the metastatic settings. This review presents a timely outline of research advances in TME biology and highlights the prospect of targeting the TME as a critical strategy to overcome acquired resistance, prevent metastasis, and improve therapeutic efficacy. As benign cells in TME niches actively modulate response of cancer cells to a broad range of standard chemotherapies and targeted agents, cancer-oriented therapeutics should be combined with TME-targeting treatments to achieve optimal clinical outcomes. Overall, a body of updated information is delivered to summarize recently emerging and rapidly progressing aspects of TME studies, and to provide a significant guideline for prospective development of personalized medicine, with the long term aim of providing a cure for cancer patients.

Cancer is one of the most fatal diseases for decades. Aggregation‐induced emission luminogens (AIEgens) have been recently used as molecular imaging or therapeutic agents in cancers, due to the advantages of large Stokes shift, high quantum yield, great biocompatibility, and strong photostability. AIEgens can specifically target different types of cancer via diverse targeting strategies. AIEgen‐based fluorescence imaging, especially near‐infrared imaging, demonstrated deep penetration and suitable signal‐to‐noise ratio, which allows reliable in vivo cancer imaging. Combined with other imaging modalities, AIEgen‐based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives. In addition, AIEgen‐based phototherapy can be used for photodynamic therapy and photothermal therapy, which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo. AIEgens nanoparticles fabricated with some specific chemicals, drugs, or siRNA, could display synergistic therapeutic effects for cancers. This paper comprehensively describes the current status and future perspectives of AIEgens, which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.

At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.

Although important progress has been made, cancer still remains a complex disease to treat. Serious side effects, the insurgence of resistance and poor selectivity are some of the problems associated with the classical metal-based anti-cancer therapies currently in clinical use. New treatment approaches are still needed to increase cancer patient survival without cancer recurrence. Herein, we reviewed two promising—at least in our opinion—new strategies to increase the efficacy of transition metal-based complexes. First, we considered the possibility of assembling two biologically active fragments containing different metal centres into the same molecule, thus obtaining a heterobimetallic complex. A critical comparison with the monometallic counterparts was done. The reviewed literature has been divided into two groups: the case of platinum; the case of gold. Secondly, the conjugation of metal-based complexes to a targeting moiety was discussed. Particularly, we highlighted some interesting examples of compounds targeting cancer cell organelles according to a third-order targeting approach, and complexes targeting the whole cancer cell, according to a second-order targeting strategy.

mRNA therapeutics have significantly evolved within the life sciences, particularly in applications such as vaccines, tumor immunotherapy, protein replacement, gene editing, and monoclonal antibody therapy. To fully realize the potential of mRNA drugs and mitigate the adverse effects, substantial vector materials have been developed for delivery of these pharmaceutical agents. Lipid nanoparticles (LNPs) represent the most clinically advanced mRNA carriers, recognized by U.S. Food and Drug Administration approved mRNA vaccines and numerous clinical trials. Diverse therapeutic applications necessitate tailored design of LNPs. Herein, we outline the principles of LNP design for mRNA delivery, focusing specifically on their effectiveness, targeting capabilities, safety profiles, and nanoparticle stability. Additionally, we present the latest advancements in mRNA‐LNP technology. This review aims to elucidate the benefits and design principles of LNP delivery systems for mRNA therapeutics, providing insights into breakthroughs and innovative ideas for further enhancing these advantages. These summaries are dedicated to promoting the broader applications of LNP‐mRNA drugs, aiming to advance the treatment of serious diseases in an effective and safe manner. mRNA therapeutics have shown substantial potential in diverse medical applications, and lipid nanoparticle (LNP) represents a clinically advanced mRNA delivery system. In this review, the critical factors affecting the function of LNPs will be elaborately discussed from the aspects of mRNA delivery effectiveness, targeting capabilities, safety profiles, and nanoparticle stability.

Abstract African swine fever (ASF), caused by the highly contagious African swine fever virus (ASFV), poses a significant threat to domestic and wild pigs worldwide. Despite its limited host range and lack of zoonotic potential, ASF has severe socio-economic and environmental consequences. Current control strategies primarily rely on early detection and culling of infected animals, but these measures are insufficient given the rapid spread of the disease. Developing effective therapeutics against ASFV is crucial to prevent further spread and mitigate economic losses. Although vaccination remains critical, recent vaccine approvals in Vietnam have raised safety and efficacy concerns. Moreover, as challenges persist in vaccine development and deployment, particularly in complex field conditions, antiviral agents have emerged as a critical complementary approach. These agents have the potential to mitigate side effects and control viral spread when vaccines alone are insufficient or when animals face simultaneous exposure to vaccine strains and wild-type viruses. However, advancing them from proof-of-concept to widespread practical application entails a significant interdisciplinary effort, given the logistical and economic constraints of in vivo testing. In this review, we examine emerging antiviral approaches and highlight key ASFV replication mechanisms and therapeutic targets to guide rational drug design amidst an evolving viral landscape. This review provides an updated synthesis of recent advances in ASF antiviral strategies, identifying key viral replication mechanisms and therapeutic targets, and emphasizes the importance of coordinated efforts to overcome experimental constraints and translate these findings into effective means of disease control.