RSC Advances
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2016
·Vol. 6
·期 80
·76905-76914
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IF 3.289
Liujie Zhang,Ying Kuang,Jia Liu,Zhilan Liu,Shiwen Huang,Renxi Zhuo
In this paper, a receptor-mediated liposomal drug delivery system (DDS) was developed aiming to deliver cisplatin (cis-diaminedichloroplatinum(II); CDDP) targeting the liver. Acetyl glycyrrhetinic acid (AGA) was chosen as the hepatic targeting ligand and acetyl glycyrrhetinic acid-poly(ethylene glycol)-stearate (AGA-PEG-ST) was synthesized. Anionic 5-cholestene-3-beta-ol-3-hemisuccinate (CHO-HS) was also synthesized. The liposomal CDDPs were prepared by employing these functional moieties with phosphatidylcholine (PC) at various ratios. Meanwhile, methoxypolyethylene glycol-stearate (MPEG-ST) with an analogous structure but without AGA was also prepared as a control. The particle sizes of AGA modified liposomes ranged from 120 nm to 180 nm and the zeta potentials were located between −39.7 mV and −3.18 mV. The liposomes had encapsulation percentages of 51.5–61.7% and a loading capacity of 23.2–26.7% for CDDP. The transmission electron microscopy (TEM) observations showed that the liposomes had spherical morphologies with homogeneous distribution. In vitro cytotoxicity of CDDP-loaded liposomes against HepG2 human liver cancer cells and A549 human lung epithelial carcinoma cells were evaluated by MTT assays. The results demonstrated that the introduction of AGA could enhance the cytotoxicity of liposomal CDDP against HepG2 cells but showed less significant impact on A549 cells. CLSM observation and FCM measurement further confirmed that AGA modified liposomes had a stronger affinity to HepG2 cells than that of liposomes without AGA. The tissue distribution of calcein in mice indicated that AGA modified liposomes resulted in higher accumulation in the liver than that of liposomes without the AGA ligand. These results demonstrated the promise of AGA decorated anionic liposomes for hepatic targeted delivery of cisplatin.
研究领域:
药剂学
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肿瘤学
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纳米医学
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药物递送系统
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肝病学
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高影响因子
Small Structures
·
2026
·Vol. 7
·期 7
·e70552
·
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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JOURNAL OF CONTROLLED RELEASE
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2026
·
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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高影响因子
Nature Communications
·
2026
·
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
·
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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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
·
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
·
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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PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2026
·
IF 4.9
Haibo Wang,Yongbing Gu,Huifen Zhu,Xianlang Chen,Yanling He,Rongrong Li,Ansheng Yu,Chenli Xu,Xiaohe Zheng,Lei Shi
Inspired by the structural motifs of Selinexor, a series of novel pyrazole-hydrazine hybrids were rationally designed and synthesized as potential reversible Exportin-1 (XPO1) inhibitors for the treatment of leukemia. The design strategy deliberately excluded the covalent warhead of Selinexor, aiming to achieve potent anti-leukemic activity through high-affinity, non-covalent interactions. Among the synthesized compounds, 5–33 was identified as the most potent candidate, demonstrating superior in vitro anti-leukemic activity against Jurkat, K562, and CMK cell lines (IC₅₀ values of 0.41, 1.01, and 0.88 μM, respectively), outperforming the positive controls Selinexor and cisplatin. Crucially, all hybrids exhibited significantly lower hepatotoxicity than cisplatin. Structure-activity relationship (SAR) studies revealed that strong electron-withdrawing trifluoromethyl groups on the pyridine ring and an electron-donating para -methoxyl group on the benzene ring were critical for potency. This was further rationalized by conceptual DFT calculations, where 5–33 displayed the most reactive electronic profile, characterized by the narrowest HOMO-LUMO gap and highest electrophilicity index. Molecular docking confirmed that 5–33 binds strongly to the XPO1 active site (-4.61 kcal/mol) via superior shape complementarity and an extensive non-covalent interaction network, aligning with the design of a reversible inhibitor. Molecular dynamics simulations further substantiated the stability of this non-covalent complex, demonstrating sustained key interactions and a high binding free energy (-33.90 kcal/mol). This study identifies 5–33 as a promising, safe, and potent lead compound for developing next-generation anti-leukemia therapeutics.
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ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Ke Li,Zhengxiang Wang,Zaigang Zhou,Huan Ding,Sheng Wu,Yuan Li,Jianliang Shen
Cuproptosis, an emerging form of mitochondrial cell death triggered by copper overload, has attracted increasing attention in tumor therapy. However, clinically available copper delivery agents lack tumor mitochondrial targeting specificity, which markedly restricts their clinical application due to their possible hepatotoxicity and nephrotoxicity. Here, we design a stepwise-targeted nanocuproptosis (MTPY-Cu@Alb), capable of sequentially targeting both tumor mitochondria to selectively induce cuproptosis. Strikingly, MTPY-Cu@Alb triggers nanocuproptosis at only 1/1000 the dosage of free copper ions, which then simultaneously reverses tumor immune tolerance mediated by copper homeostasis. Mechanistically, MTPY-Cu@Alb precisely induces cuproptosis and downregulates the immune checkpoints Cluster of Differentiation 276 (CD276) and Cluster of Differentiation 47 (CD47). By reducing these immune checkpoints, MTPY-Cu@Alb effectively reverses adaptive (CD276-associated) and innate (CD47-associated) immune resistance, thereby promoting T-cell infiltration, enhancing cytotoxic activity, and increasing macrophage phagocytosis of tumor cells. Functionally, MTPY-Cu@Alb-induced nanocuproptosis not only exhibits potent antitumor efficacy but also overcomes the chemotherapy-induced upregulation of immune checkpoints and disrupts chemotherapy-mediated resistance to cuproptosis, thereby achieving synergistic antitumor activity with chemotherapy. Collectively, this work highlights the potent ability of using MTPY-Cu@Alb as a promising mitochondria-targeted nanocuproptosis to reverse tumor immune resistance by inhibiting CD276 and CD47 expression and enhancing responsiveness to chemotherapy.
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NATURAL PRODUCT RESEARCH
·
2026
·
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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高影响因子
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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