Acta Pharmaceutica Sinica B

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A thermo-sensitive hydrogel targeting macrophage reprogramming for sustained osteoarthritis pain relief

Acta Pharmaceutica Sinica B. 2025, 15(11): 6034-6051.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.
Orally deliverable biomimetic nucleic acid therapies for targeted treatment of atherosclerosis

Acta Pharmaceutica Sinica B. 2025, 15(11): 6052-6069.

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE⁻/⁻ mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.
Tertiary lymphoid structures: The touchstone for tumor immunotherapy

Lisha Zhou, Shunji Liu, Yang Sun

Acta Pharmaceutica Sinica B. 2025, 15(11): 6070-6072.
Amino acid restriction in obesity management: Inducing energy discharge

Acta Pharmaceutica Sinica B. 2025, 15(11): 6073-6075.
Protein degradation-based anti-infective drug research

Acta Pharmaceutica Sinica B. 2025, 15(11): 6076-6081.
Unlocking the potential of targeted protein degradation via nanoparticle-based universal strategy

Acta Pharmaceutica Sinica B. 2025, 15(11): 6082-6086.
AT-17 redefines local anesthetics by targeting mitochondrial apoptosis

Acta Pharmaceutica Sinica B. 2025, 15(11): 6087-6088.
From single-thread delivery to cascading therapy: The promise of nanoCRISPR in solid tumors

Peng Mi, Horacio Cabral

Acta Pharmaceutica Sinica B. 2025, 15(11): 6089-6090.
Author correction to “Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors” [Acta Pharm Sin B 12 (2022) 952–966]

Acta Pharmaceutica Sinica B. 2025, 15(11): 6091-6092.
Self-illuminating liposome-derived in situ triggerable photodynamic therapy combining radionuclide therapy for synergistic treatment of lung cancer

Chunsen Yuan, Taotao Jin, Hangke Lei, Juanjuan Liu, Wendan Pu, Yang Zhang, Chenwen Li, Dingde Huang, Jianxiang Zhang, Jiawei Guo

Acta Pharmaceutica Sinica B. 2025, 15(10): 4973-4994.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

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