MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Hao Zhang,Dan Xie,Meng Chen,Qiangqiang Yin,Guangyue Shi,Jialong He,Xiaoyang Yu,Qian Lu,Zhengji Wang,Jing Dong,Liguo Hao
Chemotherapy is a widely used cancer treatment modality, while the complex tumor microenvironment (TME) significantly impedes drug delivery and deep tissue penetration. An MR molecular imaging drug-loaded nanomotor has been developed to achieve deep tumor tissue penetration and imaging-guided drug delivery, enabling combined photothermal and chemotherapeutic treatment of pancreatic cancer. A Janus-type nanomotor (Au@H-MP NMs) was fabricated via magnetron sputtering for application in photothermal therapy. Doxorubicin (DOX) was loaded onto one hemisphere of the nanomotor, achieving combined photothermal and chemotherapeutic treatment. Additionally, the nanomotor exhibits dual responsiveness to pH and glutathione (GSH), facilitating the controlled release of DOX within deep tumor tissues. Studies confirmed the nanomotors excellent biosafety, strong photothermal conversion capability, and effective induction of apoptosis. Tumor tissue penetration was validated through in vitro migration and infiltration assays, while in vivo experiments demonstrated significant tumor suppression and enhanced drug accumulation. Moreover, MR imaging technology enables real-time monitoring of nanomotor dynamics. These findings suggest that the synthesized Janus-type MR molecular imaging nanomotor offers a promising strategy for multimodal treatment of pancreatic cancer with significant clinical potential.
研究领域:
肿瘤学
·
生物医学工程
·
药理学
·
影像医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2021
·
IF 3.517
Jinsong Du,Lijuan Wang,Xiao Han,Jie Dou,Jiang Yuan,Jian Shen
Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, pH and glutathione (GSH) dual-responsive keratin-tannic acid (TA) complex nanoparticles were established to trigger drug release under tumor microenvironments. Reductive keratin was first extracted using a reduction method. Then, keratin-TA complex nanoparticles (KNPs) were self-assembled via non-covalent interaction and further stabilized by self-crosslinking of thiols. This method was facile and green without chemicals during the whole procedure. KNPs exhibited pH and GSH dual responsiveness as well as charge reversibility in the simulated tumor microenvironment. The anticancer drug of doxorubicin (DOX) was loaded on KNPs by hydrophobicity and hydrogen bonds. Drug-loaded KNPs accelerated drug release under mimicked tumor microenvironments, performing high toxic against A549 cells while low toxic on normal cells. Besides, drug-loaded nanoparticles could be endocytosed by tumor cells. Based on these results, KNPs may serve as drug carriers for therapeutic delivery.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Xiao Han,Lijuan Wang,Jinsong Du,Jie Dou,Jiang Yuan,Jian Shen
Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, keratin-dopamine conjugate was first synthesized by amidation reaction and then formed nanoparticles by self-polymerization of dopamine segment. Keratin-dopamine conjugate nanoparticles (KNPs) exhibited pH and glutathione (GSH) dual responsiveness in the simulated tumor environment. These nanoparticles were able to load anti-cancer drug doxorubicin (DOX) through electrostatic interactions and hydrogen bonds. These drug-loaded KNPs (DKNPs) exhibited controlled drug release in a tumor simulation environment. Meanwhile, DKNPs performed a stronger inhibitory effect on tumor cells compared with human normal tissue cells. Based on the above results, keratin-dopamine conjugate based drug carriers had a broad prospect in the field of cancer treatment.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
The resistance of cancer cells to anticancer drugs has been recognized as one of the main reasons for chemotherapy failure. Multidrug combination therapy is one of the most effective ways to solve this problem. Therefore, in this article, we designed and synthesized a pH/GSH dual-responsive camptothecin/doxorubicin (CPT/DOX) dual pro-drug synergistic treatment system with the aim of overcoming the resistance of non-small cell lung cancer A549/ADR cells to DOX. The pro-drug cRGD-PEOz-S-S-CPT (cPzT) was obtained by linking CPT to poly(2-ethyl-2-oxazoline) (PEOz) with endosomal escape properties through a GSH-responsive disulfide bond and modifying it with the targeted peptide cRGD. The pro-drug mPEG–NH–N=C-DOX (mPX) was synthesized by attaching DOX to polyethylene glycol (PEG) through acid-sensitive hydrazone bonds. The dual pro-drug micelles cPzT/mPX configured according to the CPT/DOX mass ratio of 3:1 showed a strong synergistic therapeutic effect at IC50 with a combined therapy index CI = 0.49, far less than 1. Moreover, with the further improvement of the inhibition rate, the 3:1 ratio showed a stronger synergistic therapeutic effect than other ratios. The cPzT/mPX micelles not only had better targeted uptake ability but also showed a better therapeutic effect in both 2D and 3D tumor suppression assays relative to free CPT/DOX and significantly enhanced the penetration ability into solid tumors. In addition, the results of confocal laser scanning microscopy (CLSM) showed that cPzT/mPX could effectively overcome the resistance of A549/ADR cells to DOX by delivering DOX into the nucleus to exert its effect. Thus, this dual pro-drug synergistic therapy system combining targeting and endosomal escape ability provides a possible strategy to overcome tumor drug resistance.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 34
·21328-21335
·
IF 3.108
Rujiang Ma,Chuan Zhang,Yong Liu,Chang Li,Yanling Xu,Baoxin Li,Yunliang Zhang,Yingli An,Linqi Shi
Amphiphilic block copolymer micelles in aqueous solution have been used extensively in delivery of hydrophobic drugs with the hydrophobic core serving as the reservoir. However, encapsulation of hydrophilic drugs by polymeric micelles with hydrophobic core is relatively difficult because of the poor interaction between them. Herein, we report a novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug loaded, via direct subcomponent self-assembly of block copolymer poly(ethyleneglycol)-block-poly(L-lysine) (PEG-b-PLys), 2-formylbenzeneboronic acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (e.g. capecitabine (CAPE)) under physiological pH 7.4 based on the synergistic formation of an iminoboronate structure. The PEG-b-PLys/2-FPBA micelles without CAPE are well-characterized in terms of micellization mechanism, size, morphology, pH- and GSH-responsiveness. Encapsulation of CAPE by forming PEG-b-PLys/2-FPBA/CAPE complex micelles via synergistic formation of the iminoboronate structure is discussed and pH- and GSH-responsive drug-release studies are carried out. The complex micelles are stable under physiological neutral conditions but could be destroyed in response to the stimuli of physiological acidic condition (pH 5.0) and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are successfully achieved. The drug-loaded complex micelles could be endocytosed by HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of complex micelles could be used as a promising platform for the delivery of hydrophilic 1,2-diol-containing drugs.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 6
·3084-3091
·
IF 3.119
Caixue Lin,Hailu He,Yongqi Zhang,Mingyue Xu,Feng Tian,Ling Li,Yingxi Wang
In recent years, the construction of drug carriers that integrate diagnosis and treatment has become a new trend. In this article, a metal–organic framework (Zr-MOF) was synthesized and functionalized using acetaldehyde-modified-cystine (AMC) to form the functional drug carrier Zr-MOF/AMC which could be used to determine the concentration of glutathione (GSH) for cancer diagnosis, and to achieve pH/GSH dual-responsive release of methotrexate (MTX) for cancer therapy. The cleavage of the AMC disulfide bond by GSH generates two fluorescent molecules that produce strongly enhanced fluorescence, and the intensity is proportional to the GSH concentration. The green fluorescence of Zr-MOF/AMC in cancer cells proves that it can be applied in cell imaging to detect abnormal GSH concentrations for early diagnosis. In addition, MTX loaded on the Zr-MOF/AMC is released by the cleavage of the –S–S– and –CN– bonds at the high GSH concentration and low pH in cancer cells. This dual-responsive drug release helps to deliver drugs to cancer cells more precisely. All the experiments suggest that this novel type of pH/GSH dual-responsive Zr-MOF/AMC nanoparticle may serve as a new drug delivery system for cancer diagnosis and treatment.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Qingxia Li,Rongrong Wang,Shuqi Han,Nan Shi,Jiaqi Yang,Canqi Ping,Liqing Chai,Ruili Wang,Bin Zheng,Guolian Ren,Shuqiu Zhang
Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.
研究领域:
药学
·
纳米技术
·
寄生虫学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Lu Zhang,Huan Shen,Tingting Liu,Bin Li,Xi Chen,Hong Wang,Chenyang He,Yang Liu,Gang Cao,Shuo Yu
Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor H 2 O 2 level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by H 2 O 2 self-supply, catalysts self-cycling, and GSH self-elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate H 2 O 2 and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe 3+ and Cu 2+ from CuFeMOF@GOx@Mem, which is immediately turned into Fe 2+ and Cu + by GSH, activating the Fe 2+ -mediated Fenton reaction. More importantly, Cu + can also act as an accelerator of Fe 3+ /Fe 2+ conversion, meanwhile, the generated Cu 2+ can be further reduced to Cu + by GSH. Consequently, sustained accumulation of H 2 O 2 and Fe 2+ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.
研究领域:
癌症治疗
·
纳米医学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yuting Zhang,Tao Hong,Menghui Wan,Yanbao Zhao,Lichao Peng
Responsive release systems have received extensive attention to enhance pesticide utilization efficiency and reduce environmental pollution. In this study, pH/GSH dual responsive release system based on brush-like silica (bSiO 2 ) carriers was constructed to enhance the utilization of pesticides. The bSiO 2 carriers present core-shell structure, length of 550 nm, diameter of 350 nm and shell thickness of 100 nm. The carrier had a high pesticide loading (20.0 %, w/w) for dinotefuran (Din). After loading Din, zein was covalently linked with cysteine-bridge to seal the loaded pesticides (namely Din@bSiO 2 @Zein). The Din@bSiO 2 @Zein exhibited superior foliar affinity, retention and photostability, and retention rate still remain above 95 % with 220 min UV irradiation. Din@bSiO 2 @Zein displayed pH/GSH responsive release and the cumulative release within 92 h was up to 81 % under pH=9/C GSH =6 mM, mimicking the microenvironment of lepidopteran. The Din@bSiO 2 @Zein possessed good control efficacy against Plutella xylostella . Appreciably, Din@bSiO 2 @Zein could be transported bi-directionally to various regions of tobacco plants within 24 h, which had potential to promote pesticide efficacy. This work offers a strategy to minimize the pesticide dosage and encourage sustainable agricultural development.
研究领域:
农业科学
·
纳米技术
·
农药科学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Xiaoyong song,Zejun Lin,Guozhou Cao,Xu Zhang,Nan Wang,Xiao–kun Ouyang
Nanomedicines can overcome several limitations of traditional chemotherapeutics such as imprecise targeting and severe side effects. However, challenges remain in selective delivery, targeted accumulation, and spatiotemporal control of release. This study aims to develop a pH- and glutathione (GSH)-responsive nanodrug delivery system that integrates photothermal therapy (PTT) and chemotherapy. We designed and synthesized degradable hollow mesoporous organosilica nanoparticles (DHMONs) with tetrasulfide bonds, which were self-assembled with copper sulfide nanoparticles (CuS NPs) via surface modification. These DHMONs@CuS nanoparticles utilize the hollow structure for a large surface area and high drug-loading capacity, enabling the encapsulation of the chemotherapeutic drug doxorubicin (DOX) for synergistic photothermal-chemotherapeutic treatment. Additionally, the surface modification of these nanoparticles with hyaluronic acid (HA) facilitates active targeting of tumor cells overexpressing CD44 receptors. The system exhibits dual responsiveness to pH and GSH, aiding precise drug release within the tumor microenvironment. Following studies demonstrate that this nanosystem effectively inhibits tumor growth, showing promising prospects for application in multimodal cancer treatment.
研究领域:
纳米医学
·
癌症治疗
·
药物输送系统
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-17
·
IF 10.6
Wang Yaping,Zhang Xun,Ma Yunfeng,Zhou Xiaobo,Xu Weijun,Qin Sida,Yang Chengcheng
As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu 2+ , 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O 2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer. Graphical Abstract
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）