In the tumor microenvironment (TME) of breast cancer, tumor-associated macrophages (TAMs) predominantly exhibit a pro-tumor M2 phenotype. These M2 TAMs significantly exacerbate breast cancer malignant progression through multiple mechanisms: they secrete growth factors and cytokines to promote the proliferation, invasion and migration of tumor cells; they facilitate tumor metastasis by inducing angiogenesis and remodeling the extracellular matrix; and they mediate the resistance of tumor cells to chemotherapy, targeted therapy and immunotherapy by providing survival signals, etc., leading to drug resistance. Consequently, TAMs are pivotal drivers of breast cancer initiation, progression, metastasis, and therapy resistance. With its excellent targeting, drug-carrying diversity and microenvironmental response properties, the nano-delivery system provides a new strategy for targeting and regulating the phenotypic polarization of TAMs by remodeling the inflammatory environment, modulating oxidative stress and immune signaling networks, and regulating the metabolic reprogramming of glucose, lipids, and amino acids, making it a key research direction for reversing TME, which has an important potential for clinical translation. This review systematically summarizes the critical impact of TAM phenotypic polarization on breast cancer pathogenesis, metastasis, and drug resistance, alongside nano delivery-based strategies for TAM reprogramming and the underlying molecular network mechanisms they regulate, aiming to provide new insights for the precision treatment of breast cancer.

The transdermal delivery system of traditional Chinese medicine (TCM) has emerged as a vital alternative to conventional administration routes, particularly for chronic disease management, owing to its advantages in avoiding hepatic first-pass effects, maintaining stable blood drug concentrations, improving patient compliance, and enabling sustained release. However, the efficiency of TCM transdermal delivery is significantly constrained by the "brick-and-mortar structure" barrier of the stratum corneum and the inherent complexity of TCM components, which also complicates quality control and mechanistic studies. To address these challenges, innovative strategies have been developed in recent years, including microneedles, nanocarriers (liposomes, nanoemulsions, polymeric nanoparticles, nanocrystals and self-assembled nanomicelles), permeation enhancers, iontophoresis, and sonophoresis. Synergistic permeation-enhancing strategies further overcome limitations of single-technique approaches. These technologies demonstrate substantial clinical value in dermatological therapy, pain management, wound healing, and related fields.

The elusive in vivo fate of nanomedicines represents a critical barrier to their clinical translation. Recent rapid advancements in imaging technologies, such as fluorescence imaging (FLI), photoacoustic imaging (PAI), radionuclide imaging (RI), magnetic resonance imaging (MRI), and multimodal imaging (MI) have provided powerful tools for real-time and in situ analysis of nanomedicine behavior in vivo, encompassing morphological evolution, drug release kinetics, distribution, metabolic and so on. However, significant challenges persist, particularly in continuously tracking dynamic morphological changes throughout their entire lifecycle and achieving accurate quantitative analysis within the physiological microenvironment. This review focuses on recent progress in understanding the in vivo fate of nanomedicines, systematically summarizing the fundamental principles, applications, advantages and limitations of these imaging technologies. It also highlights recent breakthroughs in utilizing these technologies to decipher the in vivo fate of nanomedicines and explores future perspectives, such as the development of innovative probes and the integration of multimodal imaging platforms. The objective is to offer robust theoretical and technical foundations for optimizing the design of nanodrug delivery systems and promoting their clinical translation.

Oral mucositis (OM) is a common complication of radiotherapy and chemotherapy in cancer patients. The severe pain and ulcer caused by OM not only significantly impair patients' quality of life but may also lead to the interruption of antitumor therapy. Currently, topical drug administration remains the preferred strategy for the prevention and treatment of OM. However, conventional dosage forms (e.g., mouthwash, gel) are susceptible to salivary clearance, exhibiting pharmacokinetic limitations such as short mucosal retention time and rapid drug clearance. In recent years, novel drug delivery systems, including nanocarrier, microneedle and hydrogel, have demonstrated significant advantages in enhancing mucosal drug targeting and prolonging therapeutic duration due to their excellent biocompatibility and controlled release properties. This review summarizes the recent research progress of the above three drug delivery systems in the prevention and treatment of OM, discusses current challenges faced by advanced delivery technologies, and outlines future research directions, aiming to provide insights for the development of more effective therapeutic strategies for OM.

Stem cell-like memory T cells (T_SCM), a subpopulation of T cells that combines features of both memory cells and stem cells, are capable of rapidly secreting immune cytokines and differentiating into effector T cells with tumor-killing ability after antigenic stimulation, thereby providing a lasting impetus for the anti-tumor immune response. Therefore, inducing T_SCM generation to bolster T cells' resistance to exhaustion, thereby improving tumor immunotherapy efficacy, has emerged as a major research focus. Nano-based drug delivery system (NDDS) possesses the qualities of in vivo targeted delivery and facilitated drug penetration, which provides the potential feasibility of inducing T_SCM strategy for clinical application. Based on this, this paper systematically describes the characteristics of T_SCM, reviews the current regulatory methods to induce and maintain T_SCM function, and summarizes the research progress of nano-based drug delivery system in regulating T_SCM for anti-tumor therapy, to provide reference and ideas for the application of induced T_SCM generation strategies in the clinic.

The gastrointestinal tract harbors the largest mucosal immune system, and tumor vaccines can leverage this advantage through oral administration to achieve enhanced immune responses. However, vaccines administered orally may encounter multiple physiological barriers that hinder their full efficacy. Nanocarriers can overcome these barriers. This paper discusses the physiological barriers currently faced by oral vaccines and the efforts made by nanotechnology to overcome these barriers. It also reviews the latest research progress and clinical translation status of nanoparticle-based delivery systems for oral tumor vaccines, aiming to provide research insights for the development of oral nanovaccines for the treatment of tumor-related diseases.

Gastrointestinal mucus constitutes a critical physiological barrier in the gastrointestinal tract. Its highly glycosylated mucin network effectively hinders the transport of particles and drug molecules toward the intestinal epithelium. In oral drug delivery, effectively overcoming this gastrointestinal mucus barrier is essential for achieving efficient drug absorption. On one hand, the continuously secreted mucus layer rapidly clears ineffectively penetrating particles due to its shear-thinning rheological property. On the other hand, macromolecular drugs face significant challenges in cross-mucus diffusion when their molecular size exceeds the mucus mesh pore size. Furthermore, certain small-molecule drugs can also be retained within the mucus layer through physicochemical interactions with its components, or rapidly eliminated by the dynamic turnover of the continuously secreted mucus, consequently leading to reduced drug delivery efficiency. Therefore, enhancing the mucus-penetrating capability of drug molecules is crucial for improving their oral bioavailability. This article systematically reviews the composition, structure, physicochemical properties, and barrier characteristics of gastrointestinal mucus, along with its barrier mechanisms affecting oral drug absorption. Additionally, it discusses nanotechnology-based drug delivery strategies designed to overcome the mucus barrier. The review aims to provide a theoretical basis and design principles for enhancing mucus permeability, improving oral bioavailability, and developing highly efficient mucus-penetrating nano-formulations.

Conventional antibody discovery paradigms mainly rely on animal immunization and hybridoma screening, which results in long development lead times, high costs, and a low success rate for antibody therapeutics. Recently, artificial intelligence (AI) is constantly driving the progress of antibody drug research and development technology with advantages in large-scale proteomic data processing. It plays a great important role in the prediction of antibody structure and de novo generation of target-specific sequences, which also substantially enhances the hit rate of drug candidates. Therefore, this article aims to summarize recent developments and challenges in the application of AI technology to antibody discovery and design, while also considering the limitations to traditional methodologies. Hope to provide practical guidance for AI-driven antibody drug development.

This study aims to investigate the inhibitory effects of cryptotanshinone (CPT) on colorectal cancer (CRC) both in vitro and in vivo, and to explore its potential mechanism of action based on ferroptosis. CRC HCT116 and HCT8 cells were treated with different concentrations of CPT. Cell counting, colony formation assays, and Annexin V/PI staining revealed that CPT significantly inhibited CRC cell viability and proliferation and promoted apoptosis. A CRC patient-derived organoid (PDO) (in accordance with the regulations of the Nankai University Biomedical Ethics Committee approval number NKUIRB2025036) model was established, and cell counting, hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC) detection of the tumor marker Ki67 confirmed that CPT suppressed PDO growth and malignant proliferation. A mouse xenograft tumor model was established (in compliance with the regulations of the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine, approval number: TCM-LAEC2025259K2011). Measurements of tumor volume and weight, HE staining, and Ki67 IHC demonstrated that CPT significantly inhibited tumor growth in vivo. Further studies found that a ferroptosis inhibitor could reverse the inhibitory effect of CPT on CRC cell proliferation, and CPT showed synergistic effects with ferroptosis inducers. Western blot and other detection results showed that CPT reduced the ratio of intracellular reduced glutathione (GSH) to oxidized glutathione (GSSG), and increased the levels of 4-hydroxynonenal (4-HNE) and the lipid peroxidation product malondialdehyde (MDA). Mechanistic studies indicated that CPT decreased glutathione peroxidase 4 (GPX4) mRNA levels and protein expression in a concentration-dependent manner. In conclusion, CPT can induce ferroptosis in CRC cells through GPX4, thereby inhibiting CRC cell proliferation and exerting anti-colorectal cancer effects.

In this study, the formation mechanism of the nanophase of "Rhizoma Anemarrhenae-Gypsum" was investigated, and its compatibility, antipyretic efficacy, and underlying mechanisms were systematically evaluated via network pharmacology. Three groups, namely the Rhizoma Anemarrhenae group, the Gypsum group, and the Rhizoma Anemarrhenae-Gypsum group, were set, with all groups including both nanophase preparations and traditional decoctions. The particle size, salinity, electrical conductivity and surface tension of the solutions were determined, and these combined with transmission electron microscope (TEM) and fingerprint analysis. Targets were screened using the GeneCards and DisGeNet, an active component-target network was constructed, a PPI network was built with the help of the STRING database and Cytoscape, and GO and KEGG enrichment analysis was performed using Metascape. The antipyretic effect of the nanophase solution was verified by hematoxylin-eosin (HE) staining, Western blot and real-time PCR. The results indicated that salinity and electrical conductivity promoted the stable formation of the nanophase; and TEM revealed that timosaponin coated the Gypsum crystal structure, leading to nanoparticle formation. Fingerprint analysis identified eight common peaks (neomangiferin and mangiferin as the main components), and the chemical components of the nanophase were consistent with those of the decoction. Through network pharmacology, 31 active components of Rhizoma Anemarrhenae and Gypsum were obtained, corresponding to 138 potential targets; the number of fever-related targets was of 1 093 fever-related targets were retrieved, among which 188 overlapping targets were screened. The main KEGG enrichment pathways included epidermal growth factor receptor, interleukin-17, hypoxia-inducible factor 1 and other signaling pathways. Experimental results showed that the nanophase group of Rhizoma Anemarrhenae-Gypsum decoction significantly reduced the body temperature in febrile rats, inhibited the expression of inflammatory factors, down-regulated fever medium, up-regulated cytoprotective proteins, and suppressed the expression of related mRNA. These findings were consistent with the predictions of network pharmacology. All animal experiments in this study were approved by the Animal Experimental Ethics Committee of Harbin University of Commerce (HSDYXY-2024022). This study found that Rhizoma Anemarrhenae-Gypsum enhances its therapeutic efficacy through the nanophase, and its antipyretic mechanism involves the multi-target regulation of inflammatory pathways and central signaling molecules thereby providing both theoretical and experimental support for the modernization of traditional Chinese medicine compound prescriptions.