COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Weinan Sun,Qin Wang,Dehui Zhang,Lu Yin,Yuwei Chen,Xinzhou Zhang,Hao Liu,Liping Sun
A folate-targeted Mn 3 O 4 nanoplatform was developed for cisplatin-induced AKI. • The platform combined ROS scavenging with localized rapamycin delivery. • FA modification enhanced tubular cell uptake via an FR-associated mechanism. • RAP@Mn 3 O 4 -FA promoted AMPK/mTOR-associated autophagic flux. • Treatment improved renal function and showed progressive clearance within 120 h. Acute kidney injury (AKI) is a critical clinical syndrome characterized by an abrupt decline in renal function and is associated with substantial morbidity and mortality. Current therapeutic options remain predominantly supportive. Cisplatin-induced AKI, a clinically relevant subtype of AKI, is driven by oxidative stress, mitochondrial dysfunction, inflammatory activation, and tubular epithelial cell injury. Rapamycin, a potent mechanistic target of rapamycin (mTOR) inhibitor, has shown renoprotective potential in preclinical AKI models; however, its therapeutic application is limited by poor renal accumulation, low aqueous solubility, a narrow therapeutic window, and potential systemic toxicity. To address these limitations, a kidney-targeted nanotherapeutic was engineered by loading rapamycin onto ultrasmall manganese oxide (Mn 3 O 4 ) nanoparticles surface-functionalized with folic acid (RAP@Mn 3 O 4 -FA). This nanoplatform integrates the intrinsic ROS-scavenging activity of Mn 3 O 4 with folate receptor (FR)-mediated renal targeting, thereby enhancing intrarenal drug delivery while reducing off-target exposure. In a cisplatin-induced AKI mouse model, RAP@Mn 3 O 4 -FA improved renal function, attenuated histological injury, activated AMPK/mTOR-associated autophagy, and showed a favorable preliminary biosafety profile. These findings suggest that RAP@Mn 3 O 4 -FA is a promising kidney-targeted nanotherapeutic candidate for cisplatin-induced AKI treatment.
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Advanced Science
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2026
·
IF 14.1
Wanbing Qin,Jiaqi Huang,Manting Zhang,Wanchun Yang,Mingwei Xu,Chi Jiang,Jiekai Li,Jinjuan Wen,Qibin Huang,Shiqi Wen,Weidong Wang,Junbing He,Qinghua Liu
Cisplatin‐induced acute kidney injury (CI‐AKI) is a frequent, dose‐dependent complication in patients receiving cisplatin chemotherapy, and effective targeted treatments remain unavailable. The development of targeted therapies for CI‐AKI may improve the efficacy of chemotherapy while mitigating renal toxicity. Given that ferroptosis is a key pathological mechanism in CI‐AKI, targeted drug delivery systems against this process represent a promising therapeutic strategy. Dipeptidase 1 (DPEP1) is highly expressed in renal proximal tubular brush borders and has been associated with ferroptosis regulation and tubular injury. In this study, mesoporous polydopamine nanoparticles (MPDA NPs) were engineered for renal‐targeted delivery of cilastatin sodium (CTT), a specific DPEP1 inhibitor, through L‐serine (L‐Ser) surface modification (CTT/MPDA@L‐Ser NPs). In vitro experiments demonstrated that CTT/MPDA@L‐Ser NPs inhibited the expression of DPEP1 to upregulate the expression of the ferroptosis‐suppressing protein glutathione peroxidase 4 (GPX4), thereby suppressing ferroptosis pathways. In AKI mice, CTT/MPDA@L‐Ser NPs exhibited selective renal accumulation, significantly ameliorating serum creatinine and blood urea nitrogen levels. Collectively, CTT/MPDA@L‐Ser NPs exhibited potent therapeutic efficacy against AKI, presenting a promising strategy for targeted AKI management. In this study, MPDA NPs were engineered to encapsulate CTT. To further increase renal accumulation of CTT, L‐serine was conjugated to the surface of the MPDA nanoparticles (CTT/MPDA@L‐Ser NPs). CTT/MPDA@L‐Ser NPs inhibit DPEP1 activity, thereby restoring ferroptosis defense mechanisms through upregulation of GPX4 and SLC7A11 expression, ultimately mitigating cisplatin‐induced AKI pathology.
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JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Dongjing Wang,Xiaonan Li,Kunpeng Wei,Suyan Wang,Wen Zuo,Ze Xu,Chen Li,Hui Wang,Xueyan Zhou,Yanzhuo Zhang
Acute kidney injury (AKI) is a prevalent clinical syndrome associated with high morbidity, mortality, and a heavy medical burden. Oxidative stress, inflammation, and ferroptosis are key drivers of AKI, yet current pharmacotherapies are limited by suboptimal efficacy and systemic side effects. An efficient and precise kidney-targeted delivery system that co-delivers complementary therapeutics could overcome these challenges. Herein, we report a platelet membrane–coated, reactive oxygen species (ROS)-responsive nanozyme (BAPCs@PM) for synergistic AKI therapy. Ultrasmall CeO 2 nanodots (∼3 nm) were in situ mineralized on the outer layer of polydopamine cores, and hydrophobic baicalein was loaded into the mesoporous interior, yielding a stable and well-dispersed multifunctional composite nanozyme. Platelet membrane cloaking conferred renal targeting, immune evasion, and prolonged circulation. BAPCs@PM enabled ROS-triggered release of CeO 2 nanodots and sustained baicalein delivery at injured sites, amplifying local antioxidant, anti-inflammatory, and anti-ferroptotic activity. In a cisplatin-induced AKI model, BAPCs@PM markedly suppressed kidney injury molecule-1 upregulation, inhibited cleaved caspase-3 activation and apoptosis, enhanced mitochondrial protection, modulated macrophage polarization, reduced proinflammatory cytokine production, regulated iron homeostasis, restored glutathione peroxidase 4 expression, attenuated ferroptosis and lipid peroxidation, and ultimately improved renal function. Owing to their ultrasmall size, the ceria nanodots achieved efficient renal accumulation and rapid clearance with minimal systemic toxicity. This study provides an innovative biomimetic and responsive therapeutic strategy for AKI by combining ultrasmall nanozymes, natural bioactive molecules, and biomimetic membrane engineering.
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Nature Communications
·
2026
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IF 18.1
Peng Haibao,Zeng Youming,Huang Yang,Lin Chenyu,Lei Zeyu,Sun Peixin,Yang Jiahui,Sheng Shaoqi,Huang Yuxin,Li Xiaohui,Zhao Jiaxu,Zeng Rui,Li Cheng,Yang Wanqi,Di Xiangjie,He Sisi,Wang Yongsheng,Yang Hanting,Yang Wuli,Chi Yudan
The central nervous system is a critical reservoir for cancer metastasis, underscoring the urgent need for effective strategies for targeted drug delivery that minimize systemic side effects. Here, we present a zwitterionic polycarboxybetaine (PCB) designed to achieve selective accumulation within the tumor vasculature of brain metastases, thereby facilitating the rapid release of therapeutics without relying on external stimuli in preclinical models. PCB selectively targets the betaine-γ-aminobutyric acid transporter 1 (BGT1) at the blood-brain-tumor barrier (BBTB), enabling localized enrichment of nanoparticles within the tumor vasculature. The intrinsic mechanical flexibility of PCB activates the Piezo1 ion channel in endothelial cells, resulting in calcium ion influx and enhanced calpain activity, which together facilitate the degradation of VE-cadherin. The burst-release mechanism improves vascular permeability and compromises the integrity of the tumor vascular barrier, allowing for the swift release of encapsulated therapeutics and promoting extensive drug distribution within the tumor microenvironment. Notably, PCB encapsulating either osimertinib or cisplatin demonstrates therapeutic efficacy, intratumoral targeting, and favorable biological safety in disease models. These findings indicate that this zwitterion-functionalized platform effectively surmounts the challenges posed by the BBTB, supporting improved drug delivery and therapeutic efficacy in brain metastases.
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Inorganics
·
2026
·Vol. 14
·期 7
·183
·
IF 3.4
Xianguang Bai,Huiping Wang,Zebao Lu,Bin Li
A novel carbohydrazide-based ligand (L) and its binuclear Cu(II) complex were successfully synthesized and characterized. Structural analysis confirmed that the Cu(II) complex adopted a monoclinic crystal system with a distorted coordination configuration, in which the multidentate Schiff base ligand chelated and bridged two Cu(II) centers. The in vitro anti-tumor results revealed that the Cu(II) complex exhibited prominent cytotoxicity against five human cancer cell lines with much lower IC50values than the free ligand, copper chloride and cisplatin. Mechanistic studies demonstrated that the Cu(II) complex significantly increased intracellular ROS and MDA levels, decreased the GSH/GSSG ratio, and reduced ATP content, thereby disrupting cellular redox balance and bioenergetic metabolism. In addition, flow cytometry analysis verified that the complex effectively triggered tumor cell apoptosis. In contrast, free CuCl2showed almost no anticancer activity, indicating that the synergistic effect between the Schiff base ligand and copper ions contributed to the excellent anti-tumor performance. This work suggests that the prepared binuclear Cu(II) complex can serve as a promising candidate for developing metal-based anticancer agents.
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CHEMICAL RESEARCH IN TOXICOLOGY
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2026
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IF 4.1
Wanting Chen,Xian Zhao,Jiaxin Zheng,Zhiru Zheng,Fengxia Qin,Zunjian Zhang,Fengguo Xu,Pei Zhang
Cisplatin (DDP) is a widely used chemotherapeutic agent, but its clinical application is limited by dose-dependent nephrotoxicity. Although metabolic dysregulation is a hallmark of DDP-induced acute kidney injury (AKI), the specific changes in fatty acid oxidation (FAO)-associated metabolic programs and the enzymes linking metabolic disturbances to cell death remain incompletely defined. In this study, targeted metabolomic profiling of the kidney revealed a marked blockade of FAO, evidenced by the accumulation of fatty acids and a decrease in downstream acylcarnitines. Among FAO-related enzymes, acyl-CoA synthetase short-chain family member 2 (ACSS2) emerged as the most significantly downregulated enzyme, which was further confirmed in an ischemia/reperfusion AKI model. ACSS2 overexpression in HK-2 cells aggravated DDP-induced inflammation and apoptosis, whereas ACSS2 knockdown significantly reduced cytotoxicity and pro-inflammatory cytokine production. Furthermore, pharmacological inhibition of ACSS2 in vivo alleviated DDP-induced AKI characterized by reduced oxidative stress and improved renal function. Together, these findings indicate that targeting ACSS2 may represent a promising therapeutic strategy to mitigate DDP-induced renal injury.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Shuting Han,Jiaru Wang,Jiao Xue,Junjie Miao,Xingyu Liu,Shuhui Yin,Qian Wang,Jing Jin
Chemoresistance is a significant factor in the failure of cancer treatment. Although some chemotherapeutic combination regimens are linked to DNA damage repair processes, the therapeutic potential of TCM-derived small molecules that target these mechanisms is still underexplored. Alloimperatorin (Alloi) has demonstrated the ability to inhibit tumor growth; however, the efficacy and molecular mechanisms of its combination with chemotherapeutic agents are not yet fully understood. Here, we demonstrate that Alloi sensitizes multiple tumor cell lines to gemcitabine (GEM) both in vitro and in vivo. Using functional assays, we confirmed a potent synergistic inhibitory effect of the Alloi-GEM combination, which markedly suppressed pancreatic cancer progression in vivo with minimal adverse effects. By integrating transcriptome sequencing with network pharmacology, we identified downregulation of c-MYC and Nijmegen Breakage Syndrome 1 gene (NBS1) as a key mechanistic event, a finding subsequently validated through multiple assays. Mechanistically, the Alloi-GEM regimen induces sustained DNA damage via disruption of the c-MYC-NBS1 axis, thereby impairing the DNA damage response pathway. Collectively, our findings establish that Alloi enhances tumor sensitivity to GEM through modulation of the c-MYC/NBS1 axis and identify this combinatorial strategy as a promising approach for cancer treatment. Alloi enhances the antitumor effect of GEM by suppressing the c-MYC/NBS1 axis. Downregulation of c-MYC reduces NBS1 expression and impairs MRN complex-mediated DNA damage response signaling, including ATM/CHK2 activation and DNA repair. As a result, GEM-induced DNA damage is sustained, ultimately promoting tumor cell death. Download: Download high-res image (238KB) Download: Download full-size image
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Materials Today Bio
·
2026
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IF 11
Huaze Ding,Xinhui Huang,Peng Hu,Xiaoyan Zhang,Yulin Wang,Baiwei Mao,Jianxin Ye,Dianwen Song,Chong Zhang,Changping Wang
Acute kidney injury (AKI) represents a critical medical condition with high mortality and no effective pharmacotherapy. Mitochondrial dysfunction in proximal tubular epithelial cells (PTECs), characterized by NAD + depletion, CoQ oxidation, and reactive oxygen species (ROS) overproduction, is a central driver of tubular damage and maladaptive repair. As central metabolic molecules, NAD + and CoQ can effectively ameliorate acute kidney injury by alleviating mitochondrial oxidative stress. However, the bioavailability of NAD + is limited by its short half-life, instability, and poor membrane permeability, whereas CoQ, despite being lipophilic, lacks specific mitochondrial targeting, preventing maximal therapeutic efficacy. Here, we report carrier-free NAD + /MitoQH 2 nanoparticles (NM NPs) with ultrasmall size and ROS-responsive properties. NM NPs are designed to pass through the glomerular filtration barrier and preferentially accumulate in injured renal tubules, where they may replenish the NAD + pool and provide a pre-reduced, mitochondria-targeted ubiquinol to support the CoQ axis under oxidative stress. Through renal accumulation and ROS-responsive release, NM NPs showed therapeutic efficacy in hypoxia/reoxygenation- and cisplatin-induced AKI models, as evidenced by reduced ROS accumulation, improved mitochondrial oxidative phosphorylation, enhanced autophagy, and attenuated ferroptosis. This work presents a metabolic nanomedicine strategy based on the co-assembly of bioactive molecules to modulate the mitochondrial NAD + –CoQ axis, providing a promising platform for AKI therapy and potentially other mitochondria-associated diseases.
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Small Structures
·
2026
·Vol. 7
·期 7
·e70552
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IF 8.9
Dan Ding,Lizhi Zhou,Xinjian Lu,Ziqi Fang,Yiqun Wan,Wenbin Zhong,Hao Wan
Acute kidney injury (AKI) is associated with high mortality and remains difficult to detect at an early-stage due to the absence of distinct symptoms. Conventional clinical biomarkers, such as blood urea nitrogen and creatinine, lack sensitivity to subtle pathological changes. While histopathological examinations are sensitive, they are invasive, tedious, and risk secondary injury. These limitations highlight the urgent need for noninvasive, sensitive, rapid, and effective diagnostic strategies for AKI. To address this, we develop a dual-modality diagnostic platform (termed PKAC) that combines second near-infrared (NIR-II) fluorescence imaging with simple colorimetric urinalysis. Specifically, PKAC is a size-transformable nanoprobe comprising cyclodextrin-capped gold nanoclusters (CD-AuNCs) for signaling, an 8-arm polyethylene glycol component for size regulation, and a KTP5 peptide for renal targeting. In healthy mice, its hydrodynamic size exceeds the glomerular filtration threshold, favoring hepatic metabolism. In AKI mice, elevated reactive oxygen species (ROS) in the injured kidneys cleave PKAC, releasing CD-AuNCs for renal excretion. The in vivo NIR-II fluorescence from liberated CD-AuNCs together with the urine colorimetric readout arising from the peroxidase-like activity provides complementary and mutually reinforcing diagnostic information. Importantly, PKAC achieves a rapid early-stage AKI diagnosis, much earlier than conventional serum markers, underscoring its translational promise.
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PHYTOMEDICINE
·
2025
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IF 8.3
Jiaao Shen,Zijia Man,Weiwei Li,Mengqi Guo,Zefeng Xiang,Long Ma,Xianjiang Kang,Shuai Guo
Background The incidence and mortality rates of lung cancer have consistently ranked highest among all cancers for an extended period. Identifying specific targets and developing effective drugs is crucial. In this study, we discovered that the natural compound sophoricoside, derived from Sophora japonica, targets the TMEM16A ion channel for lung cancer treatment. Methods Whole-cell patch clamp experiments were conducted to evaluate the inhibitory efficacy of sophoricoside on TMEM16A. Molecular dynamics simulations were performed to predict the affinity and the gating-related conformational changes of sophoricoside within TMEM16A. Cell proliferation, migration, and apoptosis experiments were employed to detect the regulation of sophoricoside on lung cancer cell growth. Western blot analyses were carried out to investigate the signaling mechanisms underlying the regulation of lung cancer growth by sophoricoside. In vivo xenograft tumor models were utilized to evaluate the anticancer efficacy and biosafety profile of sophoricoside. Results Sophoricoside inhibited the TMEM16A whole-cell current in a concentration-dependent manner, with an IC 50 of 14.8 ± 1.2 μM. Molecular dynamics simulations confirmed that sophoricoside bond to the extracellular vestibular region of TMEM16A, blocking chloride ion transport by inducing constriction of the hydrophobic pore regions. Subsequently, we investigated the regulatory effects of varying concentrations of sophoricoside on the growth of LA795 cells. Knocking down TMEM16A in LA795 cells and overexpressing TMEM16A in 16HBE cells established that TMEM16A was a critical target of sophoricoside. Western blot experiments demonstrated that sophoricoside inhibited the growth of LA795 cells via the several signal transduction pathways. In vivo results revealed that sophoricoside exhibits both potent anticancer effects and satisfactory biosafety. Conclusion This study identifies the natural product sophoricoside as a potential agent targeting TMEM16A to inhibit lung cancer growth, presenting a promising candidate for lung cancer treatment drugs.
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NATURAL PRODUCT RESEARCH
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2026
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IF 1.8
Jun-Hong Liu,Qian-Lian Yin,Xue Li,Mei Qing Zhang,Lin Guo Zou,Xin Jian Song,Li Jiang,Chun Hua Liu,Yong Jun Li
A previously undescribed steroidal compound (1), together with seven known metabolites (2–8), were isolated from the 70% ethanol extract of Sagina japonica (Sw. ex Steud.) Ohwi. Structural characterisation of all compounds was achieved through spectroscopic methods, including HR-ESI-MS, UV, IR, and NMR. Notably, compounds 1–2 and 4–8 are newly recorded in the genus Sagina. Biological activity evaluation revealed that compounds 5 and 8 inhibited α-glucosidase, with acarbose as the positive control. Compounds 4 and 8 demonstrated anti-inflammatory effects relative to dexamethasone (DEX). Additionally, using cisplatin (DDP) as the reference compound 6 showed inhibitory activity against both HepG2 and Hs 683 cell lines, while 4–5 and 7 displayed anti-proliferative effects in HCT-15 cells.
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Journal of Translational Medicine
·
2026
·
IF 9.7
Gao Hengyuan,Lin Junqing,Chen Xiaobing,Su Yingshi,Huang Yibin,Zhang Yubo,Zhang Junchang,Xu Nan,Dai Xiaoyong
Background Inter-tumor heterogeneity poses significant challenges for precision therapy in thyroid cancer (TC). The conventional organoid models are limited by inefficiency and poor physiological relevance. Methods We developed droplet-engineered organoids (DEOs) using microfluidic 3D bioprinting to rapidly generate patient-derived TC models. These DEOs were characterized via histology, whole-exome and RNA sequencing, and utilized for drug sensitivity testing and metastasis modeling. Results DEOs were generated within 10 days, exhibiting superior uniformity (CV: 2.54%) and a high success rate (76%). They faithfully recapitulated the histopathological architecture, genomic landscape (92% driver gene concordance), and native immune microenvironment (CD3+/CD56+/CD68+/α-SMA+) of parental tumors. Drug screening revealed patient-specific heterogeneity, accurately mirroring clinical responses, including cisplatin sensitivity and anti-PD-1 resistance. We established a novel TC and lung organoids co-culture model, which could be used to study the TC lung metastasis. Crucially, transcriptomics identified stage-specific maturation driven by NF-κB signaling. Pharmacological inhibition of NF-κB synergistically enhanced the efficacy of dasatinib, anti-PD-1, and paclitaxel, with combination index (CI) values of 0.58, 0.45, and 0.80, respectively. Conclusions Our microfluidic platform enables rapid, high-fidelity modeling of TC, offering a scalable and physiologically relevant tool for mechanistic studies, drug screening, and personalized therapy prediction, with highly promising translational potential.
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