Acta Pharmaceutica Sinica B

Home Latest Articles

Latest Articles

Antibody-drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies

Acta Pharmaceutica Sinica B. 2026, 16(2): 1046-1058.

Despite remarkable achievements in antibody-drug conjugates (ADCs), payloads remain limited. The identification of ADC payloads with novel mechanisms will increase therapeutic options and expand indications. Herein, we describe the use of dihydroorotate dehydrogenase inhibitors (DHODHi) as a novel payload class that provides highly potent ADCs for antitumor and antiviral therapies. Technical innovations include the development of stability-controllable linkers to meet the distinct requirements of acute viral infections and chronic tumor conditions. The antitumor ADC TH-C8H exhibited significant efficacy against gastric cancer in vivo as monotherapy and enhanced efficacy when combined with the ferroptosis inducer RSL3. The antiviral ADC HG-C3 showed broad-spectrum anti-SARS-CoV-2 activity in vitro and in vivo. Our study expands the types of ADC payloads and provides novel insights into the development of innovative broad-spectrum ADCs.
An immunostimulant nanomedicine enhances radioimmunotherapy by remodeling the tumor immunosuppressive landscape after radiotherapy

Mengwan Jiang, Mingyue Chen, Wen Zou, Yingxin Xie, Jinjin Shi, Junjie Liu, Aibing Chen, Xiu Zhao

Acta Pharmaceutica Sinica B. 2026, 16(2): 1059-1073.

Studies have shown that radiotherapy (RT) has powerful immune-stimulating effects. However, RT-mediated distal tumor regression is rare in clinical practice. Here, with an animal experimental model, we found that RT shaped an immunosuppressive landscape characterized by a high-influx of myeloid-derived suppressor cells (MDSCs), and the induction of immunologically silent tumor apoptosis, hindering the efficacy of radioimmunotherapy. To address this issue, we developed a spatiotemporally controlled nanomedicine for remodeling the immunosuppressive tumor microenvironment (TME) post-RT. Decitabine (DAC)-loaded ferritin (Ft) were crosslinked via an azobenzene linker, and meanwhile encapsulated with all-trans retinoic acid (ATRA) to construct a Ft@DAC@ATRA nanoassembly (denoted as FD@ATRA), which dissociated into monodispersive Ft@DAC units in hypoxia TME. The released ATRA could eliminate immunosuppressive MDSCs, and meanwhile Ft@DAC selectively induced immunogenic pyroptosis of the tumor by targeting the transferrin receptor 1 overexpressed on the tumor to effectively activate CD8⁺ T cells. FD@ATRA treatment reshaped the tumor immune landscape post-RT with an increase of 16.8% in tumor-infiltrating IFN-γ⁺CD8⁺ T cells. Moreover, FD@ATRA-enhanced RT remained effective in large, treatment-resistant tumors, and the inhibition rate of FD@ATRA-enhanced RT on distant tumors improved by 47% compared to the RT group alone, providing an effective therapeutic approach to improve the clinical outcomes of radioimmunotherapy.
Biomimetic nitric oxide nanogenerators for synergistic gas-mild photothermal therapy of large solid tumor

Acta Pharmaceutica Sinica B. 2026, 16(2): 1074-1089.

The mild photothermal therapy of solid tumors was still bottlenecked by the uneven temperature distribution in tumor tissue and the autophagy-mediated resistance. Here, we leveraged the ultra-small size (approximately 0.32 nm) and autophagy inhibitory property of nitric oxide (NO) to overcome these limitations for enhanced gas-photothermal therapy of large tumors. An NO donor was loaded into mesoporous polydopamine and coated with tumor cell membranes for tumor-targeting delivery. The acid-triggered release of NO potently inhibited autophagy to block the pro-survival pathway of tumor cells. Besides, as a small-molecule gas, it diffused freely into deep regions and precisely eliminated the deep-seated tumor cells, resulting in approximately 90% tumor inhibition in the late-stage breast tumor model (>500 mm³). The NO gas therapy shows great potential for complementing other therapeutics for the synergistic therapy of large solid tumors.
Intratumoral immune-microbial crosstalk shaped by tumor cell-derived extracellular vesicles encapsulating berberine boosts lung cancer immunotherapy

Acta Pharmaceutica Sinica B. 2026, 16(2): 1090-1115.

The intratumoral microbiome plays a crucial role in cancer progression, prompting the development of therapies targeting it. However, due to the heterogeneous effects of intratumoral microbes, designing treatments tailored to the unique microecological characteristics of individual tumors poses a significant challenge. Here, we found significant variations in the abundance of five bacterial genera—Lysinibacillus, Stenotrophomonas, Weissella, Comamonas, and Aeromonas—between lung adenocarcinoma (LUAD) and normal tissues by analyzing single-cell transcriptomic datasets. These specific bacterial clusters were significantly associated with immune infiltrates in the tumor microenvironment (TME). After confirming their effects in mouse models, these bacterial taxa were identified as potential therapeutic targets. Through in vitro drug screening assays, berberine was identified as a promising agent that selectively inhibits harmful bacteria while sparing beneficial ones. To address berberine’s low solubility and tumor targeting issues, it was encapsulated into tumor cell-derived extracellular vesicles (EV-ber). Feature analysis demonstrated that EV-ber shifted the intratumoral microbiome profile toward an anti-tumor phenotype and enhanced anti-tumor immunity in the TME. Furthermore, EV-ber administration inhibited LUAD growth, impaired LUAD metastatic ability, and boosted the effectiveness of anti-PD-L1 immunotherapy in mouse models. In conclusion, this work demonstrates the potential of personalized intratumoral microbial re-education strategies in LUAD therapy.
A systemic immunogenic reactor leveraging modified γ-cyclodextrins for photo-controlled cancer Ca²⁺ interference via modulating MICU1

Qian Jing, Mengnan Zhao, Yan Tang, Tao Chen, Mingyan Sun, Dandan Mi, Lan Zou, Rujing Wang, Jun Lu, Sanjun Shi

Acta Pharmaceutica Sinica B. 2026, 16(2): 1116-1139.

Interference with calcium homeostasis provokes tumor cell death and immune response, providing a novel direction for tumor immunotherapy as a promising cancer treatment strategy. Nevertheless, most reported Ca²⁺-overloaded nanoinducers encounter challenges such as intricate preparation procedures, safety concerns arising from inorganic material input, and limited anti-tumor efficiency. Herein, we synthesized a biocompatible and pH-sensitive Ca-doped cyclodextrin metal-organic framework (Ca/K-MOF) as a carrier, which was then loaded with photosensitizer hypericin (HY) via a simple one-pot synthesis to form HY@Ca/K-MOF. To enhance the stability both in vitro and in vivo, we coated HY@Ca/K-MOF with a hydrophilic layer of PEG (PEGHY@Ca/K-MOF). When exposed to 590 nm photoirradiation, PEGHY@Ca/K-MOF, with its pH-responsive dissociation, the Ca²⁺ and HY mediators released at the tumor site share the responsibility of triggering intracellular Ca²⁺ disturbances, which amplified the production of reactive oxygen species (ROS) and led to mitochondrial calcium overload through modulating mitochondrial MICU1 function. Under photocontrol, this interplay between ROS generation and mitochondrial calcium overload created a bidirectional amplification effect, where each process reinforced the other, subsequently eliciting a pyroptosis-evoked immune response. Significantly, this newly constructed delivery platform effectively suppressed both primary and distant tumors without the need for additional immunological interventions. In summary, this Ca²⁺-doped MOF-based nanomaterial provides a promising approach for efficient tumor photo-controlled mitochondrial Ca²⁺ overload-pyroptosis immunotherapy.
Skin-penetrating peptides derived from computational simulation improve transdermal absorption and facilitate topical treatment of melanoma

Acta Pharmaceutica Sinica B. 2026, 16(2): 1140-1154.

Transdermal drug delivery relies heavily on the skin permeability of therapeutic agents. In order to develop a peptide-based delivery strategy for promoting transdermal absorption, the key physicochemical factors influencing skin permeability are first identified through cell-penetrating peptides (CPPs) screening and computational simulation. Penetratin exhibits the most outstanding permeability and safety among CPPs from various origins, and positive surface patch area emerges as the key property correlated with skin permeability of the peptides. Based on these findings, a precise model to predict skin permeability of the peptides is established, leading to the computational redesign of penetratin’s amino acid sequence. The transdermal delivery efficiency of optimized penetratin derivative (589WP) is significantly improved in vitro compared with wild-type penetratin and visualized through in vivo imaging. Furthermore, the anti-metabolic drug floxuridine (FUdR) is covalently conjugated with 589WP via ester linkage, leading to accelerated FUdR release due to esterase degradation. Subsequently, this conjugate is formulated into an anhydrous gel, which significantly inhibits melanoma growth with topical application, outperforming a higher dose of free FUdR without observed skin irritancy or toxicity. The peptide prediction and design approaches established herein hold great potential for advancing transdermal drug delivery.
Rapid in vivo release of paclitaxel from polymeric micelles

Haisheng He, Jianping Qi, Yi Lu, Wei Wu

Acta Pharmaceutica Sinica B. 2026, 16(2): 1155-1165.

Profiling in vivo release kinetics of drug nanocarriers is of high translational significance. However, this has remained unrealized due to the lack of direct methodologies to quantify either the total released or residual drugs. This study employed an indirect strategy, comparing pharmacokinetics and particokinetics, to estimate the in vivo release kinetics of paclitaxel (PTX) from intravenously administered mPEG-PDLLA polymeric micelles (PMs). Blood pharmacokinetics were profiled by chromatographically quantifying PTX, while particokinetics were determined following labeling PM particles by near-infrared fluorophores with aggregation-caused quenching properties. By monitoring the dynamic change in the PTX-to-copolymer ratio, the in vivo release of PTX from the PMs was estimated. The results revealed surprisingly rapid release, with over 88.2% and 99.0% of PTX released by 15 s and 5 min post-administration, respectively. It is concluded that PTX is released rapidly from PMs in vivo, and PMs may merely work as “solvents” to solubilize PTX rather than as carriers for targeted delivery.
A highly promising new avenue for targeting K-RAS: The small-molecule degrader XMU-MP-9

Acta Pharmaceutica Sinica B. 2026, 16(2): 1166-1167.
A new paradigm for treating lung cancer by targeting the intratumoral microbiome

Wei Wei

Acta Pharmaceutica Sinica B. 2026, 16(2): 1168-1169.
Author correction to “A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers” [Acta Pharmaceutica Sinica B 15 (2025) 3767–3787]

Jialing Cheng, Zhiyang Chen, Demin Lin, Yanfang Yang, Yanjing Bai, Lingshuang Wang, Jie Li, Yuchen Wang, Hongliang Wang, Youbai Chen, Jun Ye, Yuling Liu

Acta Pharmaceutica Sinica B. 2026, 16(2): 1170-1172.

Previous 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 Next

Submission

Peer Review

Staff Login