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JOURNAL OF CONTROLLED RELEASE · 2017 · IF 7.786

Enhanced tumor therapy via drug co-delivery and in situ vascular-promoting strategy

Mingxing Yin,Songwei Tan,Yuling Bao,Zhiping Zhang

Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia , drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel . The hybrid micelles could accumulate in tumor via the long blood circulation and enhanced permeability and retention (EPR) effect, promote the drug accumulation and penetration in tumor by in situ increased vascular permeability, blood perfusion and vessel density, achieve the synergistic antitumor effect of nitric oxide and paclitaxel through modified tumor microenvironment , overcome multidrug resistance and inhibit metastasis. This study presents a combinational therapy against tumor progression and spread, which shows great potential in cancer therapy of the future.

CAS / MDL: 3483-12-3 81-88-9
研究领域: 癌症治疗 · 药学 · 纳米技术 · 生物医学工程
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MOLECULAR PHARMACEUTICS · 2022 · IF 5.364

Evaluation of a Tumor-Targeting Oligosaccharide Nanosystem in BNCT on an Orthotopic Hepatocellular Carcinoma Model

Qiyao Yang,Qi Dai,Xiaoyan Bao,Yi Zhou,Yiying Lu,Haiqing Zhong,Linjie Wu,Yinglu Guo,Lihong Liu,Xin Tan,Yiyi Xia,Min Han,Qichun Wei

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD–integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.

研究领域: 癌症研究 · 纳米技术 · 放射治疗 · 药学 · 生物医学工程
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

The preparation of shikonin-based nanomedicine with robust GSH-responsiveness

Zhiyuan Liu,Rui Sun,Yaxuan Huang,Fengyun Xu,Nan Li,Wei Zhang,Pengfei Ge,Wenke Zhang

Shikonin (SHK), an active naphthoquinone pigment isolated from the root of Chinese herbal medicine has been proven to have a significant therapeutic effect on breast cancer. However, the poor water solubility as well as the lack of tumor targeting restrict the practice application of SHK molecules as chemotherapeutic agents. Here, SHK drugs were chemically conjugated to polyethylene glycol (PEG) molecules via a disulfide bond (referred to as SHK-SS-PEG) through a facile one-step strategy. The conjugates exhibited an excellent water solubility of 12.96 mM, which is ca. 7807 times as high as that of pure SHK drugs. Noteworthily, the conjugates can self-assemble into spherical micelles with an average particle size of 106 nm, facilitating in vivo delivery as well as the accumulation in tumor tissues based on the enhanced permeability and retention (EPR) effect. Moreover, the disulfide bond enables rapid cleavage of micelles and efficient release of SHK molecules from the conjugates in response to reduced Glutathione (GSH) overexpressed within tumor cells. Thanks to the GSH-responsiveness release of SHK, the conjugate-based micelles (containing 6 μM SHK) resulted in the cell killing rate of 73 % for the MCF-7 breast cancer cells after 48 h incubation, which is 45 % higher than that for the HUVEC normal cells. All these collective beneficial properties make the SHK-SS-PEG conjugate a promising candidate for the treatment of many types of cancers.

研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统
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SEPARATION AND PURIFICATION TECHNOLOGY · 2023 · IF 8.6

Constructing C-doped TiO2/β-Bi2O3 hybrids Z-scheme heterojunction for enhanced CO2 photoreduction

Chaogang Ban,Yang Wang,Jiangping Ma,Yajie Feng,Junjie Ding,Youyu Duan,Xue Liu,Bin Zhang,Jinjing Tang,Xiaoping Tao,Liyong Gan,Shuangshuang Tan,Xiaoyuan Zhou

Rational fabricating advanced photocatalysts to recycle CO 2 into solar fuel is one of the most promising approaches to simultaneously address energy shortages and global warming. TiO 2 has been widely used in photocatalytic CO 2 reduction due to its abundant reserves, non-toxicity and harmlessness etc. However, it remains significantly challenging for practical applications due to the fast electron-hole recombination. Herein, we design a direct TiO 2 based Z-Scheme heterojunction by self-assembly of C-doped TiO 2 nanoparticles on 3D hierarchical petal of flower-like β-Bi 2 O 3 (C-TiO 2 /β-Bi 2 O 3 ). In situ electron paramagnetic resonance tests, in situ X-ray photoelectron spectroscopy and theoretical calculations reveal that electrons are transferred from β-Bi 2 O 3 to C-TiO 2 due to the formation of Z-Scheme heterojunction, which greatly accelerates the separation of photogenerated carriers to promote efficient CO 2 photoreduction. Ultimately, the optimal heterojunction shows significantly enhanced photocatalytic activity for CO 2 reduction to CO (31.07 μmol g –1 h −1 ) compared to the pure TiO 2 (3.28 μmol g –1 h −1 ) without using any photosensitizers and sacrificial agents. This work provides a unique insight to design direct Z-Scheme heterojunctions and delivers a promising photocatalyst for overcoming global warming and energy-supply issues.

研究领域: 材料科学 · 环境科学 · 化学工程 · 光催化
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APPLIED CATALYSIS A-GENERAL · 2025 · IF 4.8

High-efficiency Cu2O/CuFe-LDH nanocomposite for Fenton degradation of organic pollutants: Boosted dual redox cycles

Yanrui Su,Xiaoyu Li,Zimu Gao,Jiajia He,Zizhen Liu,Linjun Duan,Tian Sun,Jiaoge Wu,Dan Liang,Chaojun Wei,Faying Fan,Wa Gao

The incorporation of dual redox sites within catalytic materials for H 2 O 2 activation represents a promising approach to enhance the efficiency of pollutant decomposition. In this study, Cu 2 O modified CuFe-LDH nanocomposite (Cu 2 O/CuFe-LDH) was successfully synthesized via in situ topotactic transformation of CuFe-LDH. The catalytic degradation performance of the Cu 2 O/CuFe-LDH nanocomposite was investigated utilizing tetracycline hydrochloride (TCH) as a typical antibiotic contaminant. It demonstrated exceptional catalytic activity, achieving a TCH elimination rate of 93.0 % in 60 min. A rate constant value of 0.0426 min −1 was calculated for the pseudo-first-order kinetic model, which was 1.6 times and 5.0 times higher than those of CuFe-LDH and Cu 2 O, respectively. Moreover, the Cu 2 O/CuFe-LDH nanocomposite demonstrated remarkable cycling stability (85 % degradation rate after 5 recycling cycles), a wide pH range (3−11), resistance to background ion interference, and lower toxicity of the products of degradation. Based on radical scavenger tests and electron paramagnetic resonance (EPR) spectroscopy, it was verified that TCH degradation was mediated by 1 O 2 , •OH and •O 2 - , with 1 O 2 playing an essential role. X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) investigations indicate that the remarkable catalytic efficacy of Cu 2 O/CuFe-LDH is predominantly due to the synergistic interactions between Cu 2 O and CuFe-LDH, with Cu 2 O promoting the accelerated dual Cu 2+ /Cu + and Fe 3+ /Fe 2+ cycling. Thus, the Cu 2 O/CuFe-LDH nanocomposite exhibits exceptional efficiency, environmental friendliness and recyclability, rendering it an ideal candidate for practical wastewater treatment applications.

研究领域: 环境科学 · 材料科学 · 化学工程 · 纳米技术 · 催化
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 41 ·9492-9501 · IF 5.344

A tumor-targeted theranostic nanomedicine with strong absorption in the NIR-II biowindow for image-guided multi-gradient therapy

Qi Chen,Ziliang Zheng,Xiaojing He,Shuo Rong,Yufei Qin,Xiaoyang Peng,Ruiping Zhang

Developing new strategies to enhance drug accumulation in the tumor and therapeutic efficacy is of great importance in the field of tumor therapy. Herein, a peanut-like multifunctional nanomedicine (CuS-PGH NMs) made of CuS nanoparticles encapsulated in poly(L-lysine)(PLL)/glucose oxidase (GOx)-hyaluronic acid (HA) shells has been constructed via layer-by-layer (LbL) assembly, and shows good biocompatibility and effective multi-gradient therapy. Because of the enhanced permeability and retention (EPR) effect, the CuS-PGH NMs could significantly enhance the cellular uptake by tumors overexpressing CD44 receptors, which respond to hyaluronidase (HAase)-triggered surface charge conversion. Once internalized by the tumor, GOx was the first to be exposed and could effectively deplete endogenous glucose for starvation therapy, and the excess H2O2 was then converted into highly toxic hydroxyl radicals (˙OH) via a Cu+-mediated Fenton-like reaction for chemodynamic therapy (CDT). Meanwhile, the as-obtained Cu+ ions accompanied the regenerated less-active Cu2+ ions. Interestingly, the high content of H2O2 could, in turn, accelerate Cu2+/Cu+ conversion to promote the Cu+–H2O2 reaction for enhanced chemodynamic therapy (CDT), thereby achieving efficient tumor growth suppression via synergistic starvation/CDT therapy. Subsequently, owing to the strong NIR-II absorption capability of CuS-PGH NMs, effective photothermal tumor ablation of the weakened tumor cells could be realized with the precise guidance of NIR-II PAI. This multi-gradient therapeutic strategy has been demonstrated to have excellent antitumor activity with minimal nonspecific damages, and offers a new avenue to precise tumor therapy.

研究领域: 纳米医药 · 肿瘤治疗 · 生物医学工程 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2016 ·Vol. 8 ·期 20 ·10832-10842 · IF 7.76

“Sheddable” PEG-lipid to balance the contradiction of PEGylation between long circulation and poor uptake

Caiyan Zhao,Hongzhang Deng,Jing Xu,Shuyi Li,Lin Zhong,Leihou Shao,Yan Wu,Xing-jie Liang

PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a “sheddable” PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the “sheddable” PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this “sheddable” PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy.

CAS / MDL: 75-89-8
研究领域: 药剂学 · 纳米技术 · 肿瘤学 · 药物递送系统
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Liposomes-mediated enhanced antitumor effect of docetaxel with BRD4-PROTAC as synergist for breast cancer chemotherapy/immunotherapy

Xixi Chen,Fang Li,Binghui Cui,Qingyi Yan,Caisheng Qiu,Zengyan Zhu,Lijuan Wen,Weiliang Chen

It has been reported that proteolysis-targeting chimeras (PROTACs) can effectively degrade intracellular oncogenic proteins, providing an ideal strategy for cancer treatment. ARV825, a bromodomain-containing protein 4 (BRD4)-PROTAC, has demonstrated the capacity to enhance the antitumor effect of the classic chemotherapeutic agent docetaxel (DTX). However, there are three major challenges to the broader in vivo application of ARV825: poor solubility, poor permeability, and off-target effects. Additionally, the efficient co-delivery of ARV825 and DTX to tumor tissues for a synergistic therapeutic effect remains unresolved. In this study, liposomes were utilized as co-delivery vehicles for ARV825 and DTX to effectively address these issues. The well-established liposomes significantly improved the solubility of both ARV825 and DTX while maintaining a sustained release profile in blood-mimetic conditions. The co-loaded liposomes accumulated in tumor tissues via the enhanced permeability and retention (EPR) effect. After internalization, ARV825 effectively degraded intracellular BRD4 proteins and downregulated the expression of both Bcl-2 and PD-L1 proteins, thereby increasing tumor cell apoptosis and enhancing the tumor immune response. This, in turn, augmented the antitumor effect of DTX in vivo without undesired side effects. In conclusion, BRD4-PROTAC may serve as a promising synergistic agent alongside the conventional chemotherapeutic agent DTX, with liposomes functioning as effective co-delivery vehicles.

CAS / MDL: 97281-47-5
研究领域: 肿瘤学 · 药学 · 免疫学
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APPLIED SURFACE SCIENCE · 2021 · IF 6.707

A Z-scheme Pd modified ZnIn2S4/P25 heterojunction for enhanced photocatalytic hydrogen evolution

Ziyu Xie,Jing Chen,Yanxin Chen,Tianming Wang,Xia Jiang,Yiming Xie,Can-Zhong Lu

Pd modified ZnIn 2 S 4 /P25 (Pd@ZnIn 2 S 4 /P25) heterostructures have been synthesized by hydrothermal and photo-reduction method. The H 2 evolution rate of optimal photocatalyst 0.5 %Pd modified 5ZnIn 2 S 4 /2P25 (0.5 %Pd@5ZnIn 2 S 4 /2P25) are approximately 9100 and 3693 μmol · g −1 h −1 under simulated sunlight and visible light irradiation with ethanol as the sacrificial agent, which are nearly 9 and 460 times higher than pure ZnIn 2 S 4 and P25, respectively. The promoted photocatalytic performance can be attributed to the physicochemical properties of the catalysts and the strong electronic interaction between Pd modified ZnIn 2 S 4 (Pd@ZnIn 2 S 4 ) and P25, the improved transfer rate of photo-generated electrons and holes, the inhibited recombination of charge carriers, and the enhanced light harvesting. The results of photo-electrochemistry and EPR indicate that it is a Z-scheme photocatalytic system, in which the electrons accumulate on the conduct band of ZnIn 2 S 4 and the holes assemble on the valence band of P25. This work provides an effective method to construct highly efficient photocatalytic systems for solar H 2 generation.

CAS / MDL: 102-71-6
研究领域: 材料科学 · 光化学 · 催化 · 能量转换
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Influence of lung cancer model characteristics on tumor targeting behavior of nanodrugs

Weixia Xu,Shengmin Yang,Linwei Lu,Qianzhu Xu,Sunyi Wu,Jianfen Zhou,Jiashen Lu,Xingyan Fan,Nana Meng,Yuan Ding,Xudong Zheng,Weiyue Lu

Evidence is mounting that there is a significant gap between the antitumor efficacy of nanodrugs in preclinical mouse tumor models and in clinical human tumors, and that differences in tumor models are likely to be responsible for this gap. Herein, we investigated the enhanced permeability and retention (EPR) effect in mouse lung cancer models with different tumor growth rates, volumes and locations, and analyzed the nanodrug tumor targeting behaviors limited by tumor vascular pathophysiological characteristics in various tumor models. The results showed that the fast-growing tumors were characterized by lower vascular tight junctions, leading to higher vascular paracellular transport activity and nanodrug tumor accumulation. The paracellular transport activity increased with the growth of tumor, but the vascular density and transcellular transport activity decreased, and as a result, the average tumor accumulation of passive targeting nanodrugs decreased. Orthotopic tumors were rich in blood vessels, but had low vascular transcellular and paracellular transport activities, making it difficult for nanodrug accumulation in orthotopic tumors via passive targeting strategies. The antitumor efficacy of passive targeting nanodrugs in various lung cancer-bearing mice validated the aforementioned nanodrug accumulation behavior, and nanodrugs based on the angiogenesis-tumor sequential targeting strategy achieved obviously improved efficacy in orthotopic lung cancer-bearing mice. These results suggest that the EPR effect varies in different tumor models and should not be used as a universal targeting strategy for antitumor nanodrugs. Besides, attention should be paid to the animal tumor models in the evaluation of nanodrugs so as to avoid exaggerating the antitumor efficacy.

CAS / MDL: 361-09-1 9036-19-5
研究领域: 肿瘤学 · 药学 · 纳米技术
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POLYMER SCIENCE SERIES A · 2021 ·Vol. 63 ·期 6 ·769-778 · IF 1.206

Study on the Preparation and Properties of Highly Stable Micelles Sealed by Hydrogen Bonds

Yu Lili,Yao Lin,Yang Kuan,Fei Wenling,Chen Qingqing,Qin Lan,Liu Shaojing,Zou Zengqiang,Qin Bei

Abstract The surface cRGD modified polymeric (PMMA- b -PPEGMA-RGD) micelles were constructed by a combination of two-step atom transfer radical polymerization (ATRP), azide reaction, click reaction, deprotection, self-assembly of amphiphilic polymers, and addition reaction. The self-assembled DOX-loaded micelles had spherical morphology. The average size of DOX-loaded micelles measured by scanning electron microscopy (SEM) and dynamic light scattering (DLS) was less than 200 nm. According to the enhanced permeability and retention (EPR) effect of solid tumors, the micelles should have the passive targeting of tumor tissues. The introduction of cRGD on the micelles surface can not only achieve the active targeting of drug carriers to tumor tissues, but also form the network hydrogen bond between the PEG unit at the hydrophilic end of the micelles and the guanidine group in RGD, to improve the uniformity of the particle size distribution and the stability of drug loading, and also achieve the slow release of drugs. The cytotoxicity of DOX-loaded micelles on SGC7901 cells in vitro indicated that PMMA- b -PPEGMA-RGD micelles could provide the same or more remarkable antitumor activity (at low dose) as DOX. The results showed that PMMA- b -PPEGMA-RGD micelles might have great potential applications in the delivery of hydrophobic anticancer drugs.

研究领域: 药剂学 · 聚合物化学 · 药物递送系统 · 癌症研究
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Biomaterials Science · 2020 ·Vol. 8 ·期 12 ·3418-3429 · IF 6.183

A pH-responsive dissociable mesoporous silica-based nanoplatform enabling efficient dual-drug co-delivery and rapid clearance for cancer therapy

Yongju He,Linjie Shao,Ibrahim Usman,Yao Hu,Anqiang Pan,Shuquan Liang,Hui Xu

The balance between tumor accumulation and renal clearance has severely limited the efficacy of mesoporous silica-based drug nanocarriers in cancer therapy. Herein, a pH-responsive dissociable mesoporous silica-based nanoplatform with efficient dual-drug co-delivery, tumor accumulation and rapid clearance for cancer therapy is achieved by adjusting the wetting of the mesoporous silica surface. At pH 7.4, the synthesized spiropyran- and fluorinated silane-modified ultrasmall mesoporous silica nanoparticles (SP-FS-USMSN) self-assemble to form larger nanoclusters (denoted as SP-FS-USMSN cluster) via hydrophobic interactions, which can effectively co-deliver anticancer drugs, doxorubicin hydrochloride (Dox) and curcumin (Cur), based on the mesopores within SP-FS-USMSN and the voids among the stacked SP-FS-USMSN. At pH 4.5–5.5, the conformational conversion of spiropyran from a “closed” state to an “open” state causes the wetting of the SP-FS-USMSN surface, leading to the dissociation of the SP-FS-USMSN cluster for drug release and renal clearance. The in vitro and in vivo studies demonstrate that the Cur and Dox co-loaded SP-FS-USMSN cluster (Cur-Dox/SP-FS-USMSN cluster) possesses great combined cytotoxicity, and can accumulate into tumor tissue by its large size-favored EPR effect and potently suppress tumor growth in HepG2-xenografted mice. This research demonstrates that the SP-FS-USMSN cluster may be a promising drug delivery system for cancer therapy and lays the foundation for practical mesoporous silica-based nanomedicine designs in the future.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 纳米技术 · 药物科学 · 癌症研究 · 药物递送系统 · 材料科学
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