Acta Pharmaceutica Sinica B

Phosphatases: An undervalued class of antitumor drug targets

Mei Wang, Peng Zhan, Yuning Song

Acta Pharmaceutica Sinica B. 2026, 16(3): 1786-1789.

Targeting MEK2 by paeoniflorin: Mechanism underlying its protection against hypobaric hypoxia-induced lung injury

Acta Pharmaceutica Sinica B. 2026, 16(3): 1790-1792.

Tuning mechanical softness as a design principle in drug delivery: A biomechanical perspective

Acta Pharmaceutica Sinica B. 2026, 16(3): 1336-1367.

The in vivo performance of drug delivery systems (DDS) is profoundly dictated by their interactions with the biomechanical environment. Consequently, actively tuning the mechanical properties of DDS, such as softness and deformability, has emerged as an important design principle for enhancing their therapeutic efficacy. By intelligently adapting to the body's complex biomechanical system, these engineered DDS can orchestrate specific biological responses, such as enhanced tissue penetration, prolonged systemic circulation, and even regulated cellular signaling pathways through mechanotransduction. This review systematically explores, from a biomechanical perspective, how to optimize the behavior of DDS in the complex biological environments by actively designing their mechanical properties. We discuss how this principle was applied across diverse platforms, including coacervates, hydrogels, Pickering emulsions, extracellular vesicles, and liposomes, to achieve enhanced therapeutic behavior for treating challenging diseases like cancer, chronic wounds, and neurological disorders. By focusing on these tunable mechanical properties, this review aims to provide a theoretical framework and insights for the future development of DDS with improved adaptability and therapeutic efficacy in clinical settings.

Aptamers targeting respiratory syncytial virus showed high inhibitory activity by blocking the G protein

Acta Pharmaceutica Sinica B. 2026, 16(3): 1762-1768.

Respiratory syncytial virus (RSV) is a major global health threat, causing severe respiratory disease in infants, the elderly, and immunocompromised individuals—often surpassing the impact of influenza. Yet, effective RSV therapies remain limited. We describe anti-RSV ssDNA aptamers, selected via Systematic Evolution of Ligands by Exponential Enrichment (SELEX), that bind the RSV glycoprotein (G) with nanomolar affinity. These aptamer-based therapeutics demonstrated potent antiviral activity against RSV. We further established that the binding domains of these aptamers are critical for their antiviral function. Our findings highlight highly active aptamers as a promising strategy to combat RSV infections.

Extracellular vesicles-derived hybrid biomimetic nanoplatforms camouflaged Golgi apparatus-targeted aggregation induced emission photosensitizer to elicit pyroptosis and immunogenic cell death for efficient antitumor photoimmunotherapy

Acta Pharmaceutica Sinica B. 2026, 16(3): 1696-1716.

Pyroptosis is a unique programmed cell death pattern, and targeting it is an effective strategy against cancer therapy by overcoming apoptosis resistance. However, Golgi apparatus-targeted aggregation induced emission (AIE) photosensitizer as pyroptosis inducer for efficient antitumor treatment has not been reported. In this study, we successfully synthesized three new AIEgens, including TMN, TBN and TCN, by changing functional groups through a reasonable molecular design strategy, which targeted mitochondria, lysosome and Golgi apparatus (GA), respectively. In vitro experiments demonstrated that TCN exhibited the strongest reactive oxygen species (ROS) production ability and significant phototoxicity. Therefore, TCN as the GA-targeted AIE photosensitizer wore biomimetic hybrid extracellular vehicles (EVs) and M1-type macrophage membranes (denoted as EM@TCN) as pyroptosis inducer were rationally designed and engineered to trigger the production of GA cytotoxic ROS in situ. EM@TCN plus white light irradiation caused GA oxidative stress and induced pyroptosis synergistic photoimmunotherapeutic, which could rebuild tumor microenvironment and improve tumor immunogenicity. Combined with αPD-L1 (anti-mouse PD-L1 antibody), the biomimetic hybrid delivery system EM@TCN significantly inhibit the both primary and distant tumors, and effectively suppress the orthotopic breast tumor. This is the first report on a hybrid nanovesicle coated GA-targeted AIE photosensitizer to induce pyroptosis for combination with αPD-L1 to enhance antitumor photoimmunotherapy.

Heterocyclic modified paclitaxel prodrug nanoassemblies for stimuli-responsive delivery via lysosomal escape

Mingyang Han, Hezhen Xu, Jun Yuan, Wenxiao Li, Hao Zhang, Hongkai Fang, Zhiyu Kuang, Yuanhao Yu, Danping Wang, Zhenzhen Zhao, Cong Luo, Bingjun Sun, Jin Sun

Acta Pharmaceutica Sinica B. 2026, 16(3): 1662-1675.

Prodrug nanoassemblies offer an innovative approach to drug delivery, but their lysosomal entrapment often impairs drug release. Notably, tertiary amine structures can undergo protonation reactions, thereby facilitating lysosomal escape through the proton sponge effect. In this study, we developed three novel paclitaxel prodrug nanoassemblies (PTX-SS-NO NPs, PTX-SS-CC NPs and PTX-SS-NC NPs) featuring distinct heterocyclic tertiary amine structures to investigate structure-activity relationships in lysosomal escape and drug delivery. Among them, PTX-SS-NC NPs demonstrated excellent lysosomal escape capability, enabling rapid drug release into the cytosol. Systematic evaluation revealed that the PTX-SS-NC NPs exhibited optimized pharmacokinetics and significant tumor accumulation, further contributing to their strong antitumor efficacy. Our findings establish heterocyclic tertiary amines as crucial design elements for overcoming lysosomal entrapment and optimizing chemotherapeutic prodrug nanoassemblies.

Distinctive molecular architectures of Gq- and Gi-coupled GLP-1 receptors

Qingtong Zhou, Jie Li, Yao Zhang, Xiaoqing Cai, Wei Han, Dehua Yang, Ming-Wei Wang

Acta Pharmaceutica Sinica B. 2026, 16(3): 1779-1785.

Exploiting eNOS activation to achieve tumor vascular normalization via endothelial transcytosis of lipid nanoparticles

Huisong Hao, Yunfei Yi, Yanan Fu, Shengjie Sun, Zhangwen Peng, Jia Tang, Yixuan Fang, Shihao Zhuang, Yaqi Ouyang, Tianqi Wang, Meiying Wu

Acta Pharmaceutica Sinica B. 2026, 16(3): 1717-1732.

Abnormal tumor vasculature greatly accelerates tumor progression and diminishes antitumor treatments. Restoring perivascular NO gradients is available to maintain tumor vessel homeostasis and promote tumor vascular normalization. However, exogenously delivering NO strategies lacks the durability to maintain precise NO localization around tumor vessels. Herein, we design a lipid nano delivery system (MC@L) and exploit endothelial transcytosis to deliver metformin (Met) and CaO₂ into tumor vascular endothelial cells (ECs) and tumor cells for achieving tumor vascular normalization-boosted antitumor immunotherapies. The Ca²⁺ and Met released in ECs could restore perivascular localization of NO by activating endothelial NOS (eNOS). Additionally, MC@L internalized by tumor cells could cause CaO₂-induced immunogenic cell death (ICD), together with hypoxia relief and acid neutralization mediated by O₂ generation and H⁺ consumption during CaO₂ degradation, thus further improving the immune effector cell functions under the accompaniment of Met-mediated inhibition of tryptophane uptake in tumor cells. Such a lipid nano delivery system greatly increases the susceptibility of 4T1 tumor-bearing mice to PD-L1 blockade efficacy.

PhenoModel: A multimodal phenotypic drug design foundation model for discovering novel potential inhibitors of multiple cancer cells

Acta Pharmaceutica Sinica B. 2026, 16(3): 1219-1232.

Phenotypic drug discovery (PDD) focuses on the observable traits or phenotype of cells or organisms in response to drug treatment, rather than relying primarily on specific molecular targets. Drugs discovered through this approach may have better therapeutic relevance, as they are tested in conditions that closely mimic human disease. In this study, we present PhenoModel, a multimodal molecular foundation model developed using our unique dual-space contrastive learning framework. This model effectively connects molecular structures with phenotypic information. PhenoModel is applicable to a range of downstream drug discovery tasks, including molecular property prediction and active molecule screening based on targets, phenotypes, and ligands. Our results demonstrate that PhenoModel outperforms baseline methods in these areas. Building from this model, PhenoScreen is developed to successfully identify several phenotypically bioactive compounds against osteosarcoma and rhabdomyosarcoma cell lines. These findings highlight the versatility of PhenoModel and its potential to accelerate drug discovery by uncovering novel therapeutic pathways and expanding the diversity of viable drug candidates.

Multivalent sulphur-modified biosilica nanostructures for bacterial enteritis therapy

Acta Pharmaceutica Sinica B. 2026, 16(3): 1643-1661.

Bacterial enteritis is a specific gastrointestinal tract disorder caused by pathogenic bacterial infection, which not only disrupts the commensal microbiota but also contributes to cascaded complications. Here, we prepared polyethyleneimine (PEI)-based mesoporous silica nanostructures, co-modified with -SH and -S-S- groups, to simultaneously eradicate the pathogenic bacteria, regulate the immune response, and reprogram the inflammatory microenvironment in the infected intestine. Referring to the multivalent sulfur modification, the -S-S- group, with its oxidizability, perturbs the glutathione balance within bacteria, while the combined reductive capacity of -SH and -S-S- scavenges excessive reactive oxygen species and mitigates inflammation-induced damage. Additionally, the well-developed nanopores with a positively charged PEI network facilitate the absorption of bacterial lipopolysaccharide, lipopeptides, flagella and cell-free DNA through hydrogen bonding and electrostatic interactions. Furthermore, the biosilica nanostructures enable the efficient encapsulation of conventional antibacterial agents, such as berberine chloride and norfloxacin, thereby achieving targeted delivery and reducing side effects, which represents a promising strategy for next-generation antimicrobial therapies.