Acta Pharmaceutica Sinica B

Editor Profiles: Guest Editors of Special Column on Hot Topic Reviews in Drug (II)

Acta Pharmaceutica Sinica B. 2026, 16(4): 1801-1801.

In situ rewiring TAMs as annihilators by “Spark-relay” nanoinitiator with flexible reactant ratio for amplifying solid tumor immunotherapy

Acta Pharmaceutica Sinica B. 2026, 16(4): 2513-2526.

Tailoring tumor-associated macrophages (TAMs) into the tumoricidal phenotype represents a high-profile strategy for tumor immunotherapy. However, the existing TAMs repolarization strategies are restricted by hostile microenvironmental stress and metabolic compensation, leading to limited anti-tumor phenotype sustainability. Herein, a “Spark-Relay” nanoinitiator (SRN) with flexible S/R reactant ratio was meticulously designed for rewiring TAMs as tumoricidal bioreactor and precisely overcome metabolic compensation. Briefly, SRN reshaped TAMs in situ relying on tissue tropism of macrophage membrane, firstly upregulating their reactive oxygen species (ROS) production via burst release of Spark element and initially shifting the TAMs into the anti-tumoral phenotype, subsequently elevating NO production by releasing Relay element, which is converted to NO via reaction with ROS and iNOS, leading to the generation of additional ROS and creating a positive feedback loop, thereby strengthening the metabolic rewiring of TAMs from passively defensive oxidative phosphorylation to positively offensive glycolysis, which significantly enhanced the antitumoral activity of TAMs and shrunk tumor immunosuppressive microenvironment, emerging as 5.5-fold increase of tumor-suppressive/supportive ratio (TSSR) of TAMs, 4.0-fold elevation of CD8⁺ T cell infiltration, contributing to a satisfactory tumoricidal efficacy and providing a cascade amplification mode for TAMs-based cancer therapeutics.

Microneedle-based delivery for autoimmune diseases: Emerging opportunities and unresolved questions

Acta Pharmaceutica Sinica B. 2026, 16(4): 2593-2594.

A spatiotemporal selective bioinspired hybrid system engineered for preventing post-thrombolysis recurrence by inhibiting the ferroptosis pathway and reprogramming macrophages

Tianjiao Hao, Bin Gao, Yuanyuan Zhou, Chang Liu, Chuanjiang Ran, Binghua Chang, Wei You, Qiyue Wang, Jun Ye, Yan Shen

Acta Pharmaceutica Sinica B. 2026, 16(4): 2570-2586.

Cardiovascular diseases induced by arterial thrombosis, such as myocardial infarction and ischemic stroke, have gradually emerged as critical threats to human life and health. Sequentially targeted delivery systems are highly desired to be developed to improve the delivery of thrombolytics and anti-inflammatory medications to the site of the thrombus, respectively, to pursue a maximized combinational effect. Herein, we developed a probiotic-platelet hybrid vesicle-targeted drug delivery system (Fer-1@PLevs-C&U) to achieve sequential anti-thrombolytic delivery against thrombus and prevent its recurrence. The hybrid vesicles (PLevs) were prepared by mixing platelet membrane with Lactobacillus plantarum-derived bacterial extracellular vesicles (Levs) and further decorated with DSPE-PEG₂₀₀₀-CREKA, achieving “point-to-point” multi-covalent targeting of thrombus components. After targeted localization to the arterial thrombotic site, Fer-1@PLevs-C&U gradually releases the thrombolytic drug urokinase-type plasminogen activator (UPA) and Ferroptosis inhibitor (Fer-1) to facilitate thrombus dissolution and regulate the inflammatory microenvironment. By enhancing the eNOS expression and reducing the secretion of inflammatory factors TNF-α and IL-6, Fer-1@PLevs-C&U significantly reduced the inflammatory microenvironment and inhibited recurrent thrombus. Therefore, Fer-1@PLevs-C&U constitutes a novel biomimetic drug delivery platform with promising therapeutic potential and practical applicability.

From target specificity to metabolic efficiency: Design and optimization of etomidate analogues for potential improvement in postoperative outcomes

Acta Pharmaceutica Sinica B. 2026, 16(4): 2420-2443.

While transient perioperative side effects of intravenous anesthetics are often tolerated, the persistent postoperative sequelae resulting from drug accumulation pose a critical threat to patient safety. Etomidate, introduced in the 1970s, remains favored for its minimal hemodynamic impact but is severely limited by sustained adrenal suppression, leading to higher mortality and poorer outcomes in critically ill patients. To address these challenges, we reframed our strategy from solely optimizing receptor specificity to enhancing metabolic efficiency, thereby reducing prolonged postoperative exposure and mitigating sustained adverse effects. Using a deep-learning based molecule optimization algorithm, we identified metabolically favorable lead compounds and synthesized 31 novel imidazole-based etomidate derivatives. Among these, ETO-4 emerged as the most promising candidate, retaining potent anesthetic activity while accelerating metabolic clearance and significantly diminishing adrenal suppression. Plasma cortisol assays confirmed the effect of ETO-4 on adrenal function is greatly reduced. These findings underscore a paradigm shift in anesthetic drug design, demonstrating that prioritizing enhanced metabolic profiles can yield safer, more effective agents that improve postoperative outcomes.

Identification of HMGB1 as a target of 3-O-benzoyl-20-deoxyingenol in NSCLC therapy using integrated ABPP and SIP

Acta Pharmaceutica Sinica B. 2026, 16(4): 2587-2592.

Astrocytes in predictive processing of emotion: Kir4.1 as precision modulator of social interaction

Acta Pharmaceutica Sinica B. 2026, 16(4): 2595-2597.

From conceptual design to translational progress: Emerging advances in intelligent microneedles for biomedical applications

Acta Pharmaceutica Sinica B. 2026, 16(4): 1804-1847.

Microneedles (MNs), as innovative biomedical devices, are undergoing a transformation from basic transdermal devices to intelligent and multifunctional systems. The advancement of intelligent MNs enhances tissue penetration and adhesion, triggers timely, on-demand and precise spatiotemporal controlled release, achieves sequential drug delivery and in situ monitoring, and enables close-loop theranostics via the integration of flexible electronics, wireless communication, and artificial intelligence. This review not only systematically highlights these cutting-edge breakthroughs, focusing on five major innovative advancements of conceptual design, including mimicking strategies, stimuli-responsive systems, innovative structural designs, living payload, and wearable integration, but also delineates the principal obstacles obstructing the advancement of intelligent MNs. We also emphasize that MN technology is fueling the evolution of next-generation medical paradigms based on its personalized, minimally invasive, and intelligent features through interdisciplinary integration, which is crucial for reshaping the future landscape of disease diagnosis and treatment.

Novel liquid-based approaches for transmucosal drug delivery

Acta Pharmaceutica Sinica B. 2026, 16(4): 2119-2152.

Advancements in drug discovery, such as artificial intelligence, computational technology, and combinatorial chemistry, have led to numerous new promising drug candidates. However, most still fail to reach the market due to poor physicochemical properties, resulting in off-target or toxic effects. As a potential solution, non-invasive and targeted drug delivery at mucosal surfaces can deliver drugs directly to therapeutic sites to avoid off-target effects, decrease required drug doses, bypass hepatic first-pass metabolism, and circumvent uncontrolled drug release. Liquid-based drug delivery systems have advanced tremendously over recent years, with novel dosage forms such as ionic liquids, liquid crystals, stimuli-responsive phase transforming liquid systems, nanoemulsions, double-emulsions, self-emulsifying delivery systems, and eutectic systems being developed. These systems hold vast promise for transmucosal drug delivery as liquids generally provide superior spreadability compared to solid dosage forms, and some liquid systems provide prolonged mucosal retention times compared to conventional solutions. However, liquid dosage forms present regulatory challenges such as preservation, sterility, and stability requirements. This review discusses novel liquid-based formulation approaches to cross the ocular-, nasal-, oromucosal-, and vaginal mucosal barriers emphasizing advanced liquid drug delivery systems and the progress made toward clinical translation as a platform for future transmucosal liquid-based dosage form development.

FTO-mediated m⁶A depletion drives prenatal prednisone exposure-induced cortical neurogenesis deficits and long-term anxiety-depression-like behaviors in offspring

Acta Pharmaceutica Sinica B. 2026, 16(4): 2375-2395.

Prednisone is widely used to treat pregnancy-complicated autoimmune diseases, but the impact of prenatal prednisone exposure (PPE) on offspring neurodevelopment is unclear. Clinical follow-up using the Ages and Stages Questionnaires (ASQ:SE-2 and ASQ-3) revealed a strong association between PPE and neurodevelopmental abnormalities. In a rat model, PPE significantly inhibited the proliferation and differentiation of cortical radial glial cells (RGCs), impairing cortical neurogenesis and leading to anxiety- and depression-like behaviors. Mechanistically, PPE upregulated fat mass and obesity-associated protein (FTO) nuclear recruitment in RGCs, depleting N⁶-methyladenosine (m⁶A) modifications and stabilizing Crebbp/Ep300 mRNA, which activated genes related to cell cycle arrest and neuronal differentiation via histone 3 at lysine 27 acetylation (H3K27ac) modifications. The key role of FTO in PPE-induced neurodevelopmental impairments was confirmed using Ep300 shRNA, Fto overexpression lentivirus, and a conditional Fto knockout mouse model (Ftofl/fl; Nestin-Cre). Notably, early postnatal neuregulin-1 supplementation promoted RGCs proliferation and alleviated behavioral abnormalities.