JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Zihao Teng,Chen Liu,Xiangfu Du,Yuchen Guo,Zhenkun Huang,Jingya Gu,Xiaohui Chen,Menghan Xiao,Shipeng Chen,Xiao-Bin Hao,Jingbo Qin,Shuaidong Huo
The intracellular balance of reactive oxygen species (ROS) is crucial for cancer cell survival and tumor development, with mitochondria playing a key role in maintaining this balance through antioxidant defenses. Despite the efficacy of ROS-modulating strategies in many tumors, certain ROS-tolerant malignancies, such as HepG2 cells, pose significant therapeutic challenges due to their robust antioxidant systems and unique redox microenvironments. In this work, we have developed a self-amplifying nanoprodrug (nCACT) designed to target ROS-tolerant tumor cells. nCACT is constructed from a prodrug conjugate that combines a glutathione (GSH)-depleting chemotherapeutic agent, a mitochondria-targeting moiety, and a ROS-stimulated amplifying linker. The nCACT leverages the enhanced permeability and retention effect for tumor accumulation and cellular uptake, followed by acid-activated drug release and mitochondrial targeting. By disrupting ROS defense mechanisms and inducing mitochondrial dysfunction, nCACT effectively elevates ROS levels and depletes GSH, suppressing cancer cell growth. Our findings demonstrate that nCACT represents a novel and powerful strategy for overcoming ROS resistance in cancer therapy, offering a promising avenue for treating ROS-tolerant malignancies.
研究领域:
肿瘤学
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药理学
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生物化学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 4
·511
·
IF 5.5
Qiao Qiao,Xian Wan,Jie Li,Weijun Chen,Enxuan Li,Lipeng Qiu,Huiming Tu
Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application.Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated.Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine.Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug.
研究领域:
药剂学
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炎症性肠病治疗
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生物材料
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
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IF 15.304
Qin Zeng,Xipeng Li,Si Xie,Da Xing,Tao Zhang
Developing single molecule-assembled nanoprodrugs that can reverse the glutathione (GSH)–mediated drug resistance of tumors provides promising potentials for precision and effective cancer theranostics. Herein, we developed a novel single molecule-assembled nanoprodrug for effective photodynamic/chemotherapeutic eradication of drug-resistant tumors via the multistage GSH-depletion. The nanoprodrug MSSP-NP could be fancily fabricated by self-assembly of an amphiphilic activatable molecular MSSP, which is synthesized by covalently conjugating the photosensitizer methylene blue (MB) with a GSH-sensitive cisplatin prodrug via a tumor targeting thiolated polypeptide . Upon the nanoprodrug MSSP-NP systematic administrated, its photoactivities and pharmacological effects can be thoroughly switched on by intracellular GSH to produce the photosensitizer MB and chemotherapeutic drug cisplatin, along with the multi-step consumption of GSH, which could remarkably boost oxidative stress and reverse the drug resistance. As a result, the nanoprodrug could effectively disrupt the tumor GSH-defense system to afford high-efficiency photodynamic/chemotherapeutic inhibition of drug resistance tumors (96.4%) with minimum side effects.
研究领域:
癌症治疗
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纳米医学
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药学
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DOI
PubMed
高影响因子
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
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2013
·Vol. 28
·期 3
·617-621
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IF 0.484
Zeng Rong,Wang Zehu,Wang Hongran,Chen Liqiang,Qiao Renzhong,Hu Liming,Li Zelin
Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5′- O -succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate (TPP) to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy (TEM), and their zeta potential, particle size, and polydispersity (size distribution) were measured by the dynamic light scattering (DLS) techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.
研究领域:
生物化学
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制药科学
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纳米医学
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产品关联
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
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IF 4.4
Naikuan Fu,Yinan Zeng,Jing Zhang,Peng Zhang,Hong Zhang,Shicheng Yang,Jianhua Zhang
The therapeutic efficacy of bortezomib (BTZ) is often limited due to low solubility, poor stability in vivo and nonspecific toxicity. Herein, a kind of catechol-functionalized polyethylene glycol (mPEG-CA) is first synthesized and then mPEG-CA is readily used to conjugate with BTZ by the formation of dynamic boronate bonds to obtain PEGlyated BTZ prodrug (mPEG-CA-BTZ) with the ability of pH-controlled disassembly and drug release. The structure and morphology, physicochemical characteristics, drug loading, and release as well as in vitro cytotoxicity of mPEG-CA-BTZ nanoparticles are investigated in detail. The results demonstrated that mPEG-CA-BTZ can not only self-assemble into nanostructures with uniform size and stable dispersion in physiological pH condition (pH 7.4) but also respond to the tumor acid microenvironment and achieve pH-controlled BTZ release by acid-triggered cleavage of boronate bonds, decomposition of mPEG-CA-BTZ and thus disassembly of mPEG-CA-BTZ nanoparticles. mPEG-CA-BTZ nanoparticles are expected to have great potential as a promising nanoplatform for pharmaceutical formulations of BTZ to increase therapeutic efficacy and decrease side effects of BTZ. Considering the easily available and biocompatible excipients and simple preparation process, the strategy designed herein provides a facile and promising approach to synergistically integrate the function of PEGylation and pH-sensitiveness into boronic acid-containing small molecule pharmaceutical agents.
研究领域:
药物化学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jianguo Wang,Jianyong Zhuo,Yaoye Tao,Shengjun Xu,Zun Chen,Fan Yang,Qinghong Ke,Haiyang Xie,Shusen Zheng,Hangxiang Wang,Xiao Xu
Background There is currently no effective treatment for advanced hepatocellular carcinoma (HCC), and chemotherapy has little effect on long-term survival of HCC patients, largely due to the cancer stem cell (CSC) chemoresistance of HCC.Methods We constructed a small-molecule nanometer-sized prodrug (nanoprodrug) loaded with salinomycin (SAL) for the treatment of HCC. SAL was encapsulated by the prodrug LA-SN38 (linoleic acid modified 7-ethyl-10-hydroxycamptothecin) to construct a self-assembled nanoprodrug further PEGylated with DSPE-PEG2000. We characterized this codelivered nanoprodrug and its antitumor activity both in vitro in human HCC cell lines and in vivo in mice.Results Delivery of the SAL- and LA-SN38-based nanoprodrugs effectively promoted apoptosis of HCC cells, exerted inhibition of HCC tumor-sphere formation as well as HCC cell motility and invasion, and reduced the proportion of CD133+ HCC-CSC cells. In nude mice, the nanoprodrug suppressed growth of tumor xenografts derived from human cell lines and patient.Conclusion Our results show that SAL-based nanoprodrugs are a promising platform for treating patients with HCC and a novel strategy for combination therapy of cancers.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zishan Zeng,Jingwen Jiang,Yue Sun,Wanzhen Li,Dong Zheng,Huanxin Lin,Chunshun Zhao
Helicobacter pylori ( H. pylori ) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori . Based on our previous discovery that Cu(DTC) 2 exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu 2+ and shikonin (SK) to eliminate H. pylori . DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu 2+ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori , DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu 2+ from Cu-SK to form Cu(DTC) 2 . The released SK possessed the bactericidal sensitization effect on Cu(DTC) 2 . The H. pylori -activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC) 2 and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.
研究领域:
医学
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2021
·
IF 3.512
Guodong Zheng,Jiahui Zheng,Le Xiao,Tongyi Shang,Yanjun Cai,Yuwei Li,Yiming Xu,Xiaoming Chen,Yun Liu,Bin Yang
In this study, a pH-responsive nano-prodrug was fabricated by conjugating emodin to the PEGylated polyethyleneimine (mPEG-PEI) with acid-sensitive boronate ester bonds. 1H NMR spectra results showed that emodin was effectively bonded to mPEG-PEI, and acid-sensitive assay further confirmed the formation of boronate ester bonds. The size and morphology of the nano-prodrug were ascertained through transmission electron microscopy (TEM) and dynamic light scattering (DLS), which showed that the prodrug has a sphere-like shape with hydrodynamic size around 102 nm at pH 7.4. Subsequently, a drug-release behavior assay was carried out to carefully investigate the acid-sensitive drug-delivery property of the prodrug. Moreover, in vitro cell viability assay confirmed the superior cytotoxic effect of the nano-prodrug against HeLa cells compared to free emodin. Furthermore, the antibacterial study showed that the nano-prodrug could inhibit the bacterial (both Gram-positive and Gram-negative) growth more effectively than free emodin. Overall, this study provides a promising paradigm of the multifunctional nano-prodrug for pH-responsive tumor therapy and antibacterial activity.
研究领域:
药剂学
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肿瘤学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
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2025
·
IF 4
Kong Chao-Ying,Luo Chu-Wen,Xu Ya-Jun,Shen Na,Tang Zhao-Hui
Given that platinum-based drugs are widely used clinically as chemotherapeutic agents, their severe toxic side effects have attracted significant attention. Consequently, the development of novel nanoprodrugs based on low-toxicity tetravalent platinum (Pt(IV)) complexes holds substantial research value. Herein, we discovered that coumarin derivatives exhibit inherent antitumor efficacy and significantly enhance superoxide anion radicals (•O 2 − ) generation in aqueous solutions under ultrasound (US) irradiation. Given that •O 2 − is known to mediate the reduction of Pt(IV) to divalent platinum (Pt(II)), we engineered an US-responsive dual-drug nanoprodrug (P-cisPt(IV)@5-MOP). This nanoprodrug was prepared by covalently conjugating Pt(IV) and methoxy polyethylene glycol hydroxyl (mPEG-OH) to a poly( l -glutamic acid) (PLG) carrier, followed by encapsulating coumarin derivatives. Under low-intensity US irradiation (1.5 W/cm 2 , 1 MHz, 10 min), P-cisPt(IV)@5-MOP achieved a Pt(IV) reduction rate of 91.4%. Furthermore, upon US exposure, its half-maximal inhibitory concentration (IC 50 ) against 4T1 breast cancer cells decreased dramatically from 25.7 µmol/L to 0.1 µmol/L. Remarkably, this system combined with US therapy yielded a tumor inhibition rate of 90.9%, with 40% of tumor-bearing mice achieving complete eradication of tumors, while exhibiting low systemic toxicity. Collectively, this work not only identifies a novel sonosensitizer capable of generating •O 2 − but also develops a new class of ultrasound-activatable Pt(IV) nanoprodrug.
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产品关联
DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 18
·12796-12806
·
IF 3.9
Weiwei Ma,Qiufeng Zhao,Shilong Zhu,Xinyue Wang,Chuangchuang Zhang,Daming Ma,Na Li,Yanyan Yin
Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Qida Hu,Fu Zhang,Bowen Li,Piaopiao Jin,Junming Huang,Zhuo Yao,Xinyu Zhao,Shiyi Shao,Meng Wang,Yuan Ping,Tingbo Liang
The desmoplastic nature characterized by dense tissue and poor vascular conditions in pancreatic cancer (PDAC) poses a significant barrier to effective chemotherapy. Targeting the extracellular matrix and reducing desmoplasia in the tumor microenvironment is a rational approach to improve the penetration and efficacy of gemcitabine (GEM) in PDAC. Herein, a small molecular self-assembly nano-prodrug is developed for the “three-in-one” co-delivery of GEM chemotherapeutics, all-trans retinoic acid (ATRA), and nitric oxide (NO) donors, decorated with PDAC-homing targeting peptide. Stimulated by the PDAC microenvironment, the nano-prodrug releases ATRA that quiesces activated pancreatic stellate cells to alleviate stromal desmoplasia. Simultaneously, it generates abundant NO to induce a vasodilatory effect as well as a “nanomotor” effect. This combinational nano-prodrug delivery strategy, with a dual enhancement of drug penetration dynamics, effectively improves the distribution and bioavailability of the co-delivered GEM into the deep and dense pancreatic tumor tissue, which leads to significant amplification of tumor growth inhibition in different PDAC mouse models.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xian Qin,Li Zhu,Xuan An,Cheng Zhang,Jiawei Li,Fei Yan,Wenjin Zhang,Kai Qu,Kun Zhang,Wei Wu,Guicheng Wu
The establishment of hybrid cell membrane-camouflaged nanotherapeutics is crucial to preserve and impart their biological functionality inherited from the source cells. In this study, one side relies on the intrinsic affinity between the intracellular domain of Band 3 in the red blood cells membrane (Rm) and P4.2 peptide-modified nanoparticles (Rm-Que/Cu), promoting the self-assembly coupling-driven encapsulation of Rm on the surface of nanodrugs. On the other side, it involves integrating the bioengineered cell membrane with high Del-1 expression (Dm) with Rm-Que/Cu to form RDm-Que/Cu, targeting the role of integrin α v β 3 on tumor neovascularization and endothelial cells (ECs). This approach simultaneously integrates the multi-functions, including self-assembly encapsulation, targeted drug delivery, and on-demand drug release. Both in vitro and in vivo experimental results confirmed that RDm-Que/Cu were able to disrupt the cellular copper homeostasis, inhibit tumor angiogenesis, and induce cuproptosis. This discovery provides a feasible platform for the biomedical application of hybrid cell membrane-camouflaged biomimetic nanotechnology.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）