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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

Implantable composite fibres with Self-supplied H2O2 for localized chemodynamic therapy

Gang Wang,Jiayu Gao,Yike Fu,Zhaohui Ren,Jie Huang,Xiang Li,Gaorong Han

The anticancer efficacy of chemodynamic therapy (CDT) is considerably restrained by the inadequate content of H 2 O 2 within tumor microenvironment (TME), unexpected oxidation of Fenton agents and low targeting efficiency of particulate therapeutic platforms. Herein for the first time, an implantable CDT platform was designed and synthesized by combining Fe 0 nanocrystal embedded mesoporous silica nanoparticles (FeMSN) and PCL-gelatin fibres (PG fibres), denoted as [email protected] fibres. FeMSN was fabricated via in situ reduction of ferrous ions within the mesopores of MSNs, and assembled at the surface of electrospun PG fibres by electrostatic interaction to form a fibrous mesh. The findings reflected that, in an acid condition, FeMSN nanoparticles can liberate from the composite fibres, and be effectively uptaken by 4T1 cancer cells. The FeMSN released may react with oxygen to generate H 2 O 2 in the acidic microenvironment, and subsequently transform H 2 O 2 to intracellular hydroxyl radicals, inducing enhanced cell-killing effect. By implanting the composite fibres locally at the tumor site of mice, promoted anticancer efficacy was observed with comparison of the intratumoral-injected FeMSN nanoparticles. This study suggests that [email protected] composite fibres can serve as a potential localized PDT platform for effective antitumor purposes, which may spark a series of follow-on investigations for localized cancer therapeutic technology.

CAS / MDL: 7782-63-0 75-89-8
研究领域: 癌症治疗 · 材料科学 · 纳米技术 · 生物医学工程
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ACS Nano · 2023 · IF 17.1

Hypoxia-Responsive Golgi-Targeted Prodrug Assembled with Anthracycline for Improved Antitumor and Antimetastasis Efficacy

Chenqi Guo,Mengying Wu,Zhaofei Guo,Rongping Zhang,Zijun Wang,Xiong Peng,Jianxia Dong,Xun Sun,Zhirong Zhang,Peihong Xiao,Tao Gong

Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified and secreted by swollen Golgi apparatus in tumor cells. Thus, Golgi complex is considered as an important target for the remedy of metastasis. Currently, Golgi targeting technologies are mostly employed in Golgi-specific fluorescent probes for diagnosis, but their applications in therapy are rarely reported. Herein, we proposed a prodrug (INR) that can target and destroy the Golgi apparatus, which consisted of indomethacin (IMC) as the Golgi targeting moiety and retinoic acid (RA), a Golgi disrupting agent. The linker between IMC and RA was designed as a hypoxia-responsive nitroaromatic structure, which ensured the release of the prototype drugs in the hypoxic tumor microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), an anthracycline, to form a carrier-free nanoparticle (NP) by emulsion-solvent evaporation method. A small amount of mPEG2000-DSPE was added to shield the positive charges and improve the stability of the nanoparticle to obtain PEG-modified nanoparticle (PNP). It was proved that INR released the prototype drugs in tumor cells and hypoxia promoted the release. The Golgi destructive effect of RA in INR was amplified owing to the Golgi targeting ability of IMC, and IMC also inhibited the protumor COX-2/PGE2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary tumor and its pulmonary and hepatic metastasis. The small molecular therapeutic prodrug targeting Golgi apparatus could be adapted to multifarious drug delivery systems and disease models, which expanded the application of Golgi targeting tactics in disease treatment.

CAS / MDL: 1122-58-3
研究领域: 肿瘤学 · 药学 · 纳米技术 · 药物递送系统
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY · 2015 ·Vol. 15 ·期 6 ·4111-4118 · IF 1.556

Effective PEGylation of Fe3O4 Nanomicelles for In Vivo MR Imaging

Song Lina,Zang Fengchao,Song Mengjie,Chen Gong,Zhang Yu,Gu. Ning

In this strategy, a magnetic fluid of the Fe3O4 nanomicelles was synthesized with amphiphilic PEGylated phospholipid as surfactant and soybean oil as stabilizer under simple mechanical stirring and subsequent ultrasonication. Transmission electron microscope (TEM) measurement indicated that the sample is monodisperse spherical Fe3O4 nanoparticles with internal core size of 9 nm and external nanomicelle shell thickness of 1.5 nm. The final hydrodynamic size of the sample is 19.5 nm and its zeta potential is −38.5 mV, suggesting good stability of the magnetic nanomicelles in water. To assess the ability of magnetic nanomicelles to escape reticuloendothelial system (RES) uptake, in vitro cell phagocytosis experiments were conducted using murine macrophages (RAW264.7). The results indicated that the PEGylation can effectively prevent the uptake of the nanomicelles by the macrophages. Using a mouse model of 4T1 breast cancer, the nanomicelles provided a good magnetic resonance imaging (MRI) capability to sensitively detect tumor by enhanced permeability and retention (EPR) effect. The PEGylated monodisperse magnetic nanomicelles would become a potential contrast agent for passive targeting diagnosis of tumor by MR imaging.

研究领域: 纳米技术 · 医学成像 · 癌症研究 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2020 ·Vol. 16 ·期 46 ·2004240 · IF 11.459

Nanoparticle-Enabled Dual Modulation of Phagocytic Signals to Improve Macrophage-Mediated Cancer Immunotherapy

Ya-Ru Zhang,Jia-Qi Luo,Jing-Yang Zhang,Wei-Min Miao,Jia-Si Wu,Hua Huang,Qi-Song Tong,Song Shen,Kam W. Leong,Jin-Zhi Du,Jun Wang

Activation of the phagocytosis of macrophages to tumor cells is an attractive strategy for cancer immunotherapy, but the effectiveness is limited by the fact that many tumor cells express an increased level of anti-phagocytic signals (e.g., CD47 molecules) on their surface. To promote phagocytosis of macrophages, a pro-phagocytic nanoparticle (SNPA CALR&aCD47 ) that concurrently carries CD47 antibody (aCD47) and a pro-phagocytic molecule calreticulin (CALR) is constructed to simultaneously modulate the phagocytic signals of macrophages. SNPA CALR&aCD47 can achieve targeted delivery to tumor cells by specifically binding to the cell-surface CD47 and block the CD47-SIRPα pathway to inhibit the “don't eat me” signal. Tumor cell-targeted delivery increases the exposure of recombinant CALR on the cell surface and stimulates an “eat me” signal. Simultaneous modulation of the two signals enhances the phagocytosis of 4T1 tumor cells by macrophages, which leads to significantly improved anti-tumor efficacy in vivo. The findings demonstrate that the concurrent blockade of anti-phagocytic signals and activation of pro-phagocytic signals can be effective in macrophage-mediated cancer immunotherapy.

CAS / MDL: 3326-32-7 81-88-9
研究领域: 癌症免疫学 · 纳米技术 · 免疫疗法 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2013 · IF 7.604

Anti-tumor effects in mice induced by survivin-targeted siRNA delivered through polysaccharide nanoparticles

Feifei Yang,Wei Huang,Yunfei Li,Shan Liu,Mingji Jin,Yuli Wang,Lihua Jia,Zhonggao Gao

Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility . TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA Sur targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA Sur nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 癌症生物学 · 药学 · 纳米技术 · 分子生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

A pH-responsive chiral mesoporous silica nanoparticles for delivery of doxorubicin in tumor-targeted therapy

Kaijun Gou,Wei Xin,Jinying Lv,Zihao Ma,Juqin Yang,Lin Zhao,Ying Cheng,Xuchun Chen,Rui Zeng,Heran Li

The purpose of this study was to develop a nano-drug delivery system with intelligent stimuli-responsive drug delivery in tumor microenvironment (TME). Based on chiral mesoporous silica nanoparticles (CMSN) with a chiral recognition function in our previous research, a pH-responsive CMSN (CS-CMSN) was successfully prepared by chemical modification of chitosan (CS), and the related physicochemical properties, drug release performance, potential anti-tumor effect, and biological safety were studied. The results showed that the CS-CMSN were successfully modified by CS. Moreover, CS-CMSN displayed superior encapsulation ability for doxorubicin (DOX) and exhibited controllable pH-responsive drug release properties. In particular, in a physiological environment (pH 7.4/6.5), CS shielded the nanopores , prevented DOX release, and minimized side effects on normal cells. Once the CS-CMSN was exposed to the TME (pH 5.0), the pH-sensitive moiety of CS was cleaved in an acidic environment, along with the rapid release of DOX. In vitro cell experiments further proved that [email protected] was more strongly taken up by 4T1 cells and could enhance the toxicity to 4T1 tumor cells as well as promote cell apoptosis. More importantly, CS-CMSN were shown to have good biosafety in vitro and in vivo . Overall, the delivery of DOX by CS-CMSN nanocarriers is a promising strategy for tumor-targeted therapy.

CAS / MDL: 6066-82-6 78-10-4
研究领域: 药学 · 纳米技术 · 癌症治疗 · 生物医学工程
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ChemNanoMat · 2022 ·Vol. 8 ·期 12 ·e202200424 · IF 3.82

FeOCl Nanodots and Doxorubicin Co-loaded Polymer Nanoparticles for Glutathione/pH-responsive Chemodynamic Therapy/Chemotherapy of Tumors

Lihui Yuwen,Yue Zhang,Huayu Xiao,Hang Xiao,Xiao Li,Wenjing Yang,Zhaoxia Yang,Heng Dong,Lianhui Wang

Graphical FeOCl nanodots were prepared by a ball-milling method and used as novel Fenton agents. Glutathione/pH dual-responsive polymer nanoparticles were synthesized by co-polymerization of acrylic acid and 3-methacrylamido dopamine with a cross-linker containing disulfide bonds, which can load FeOCl nanodots and doxorubicin to form a multifunctional nanoplatform for efficient chemodynamic therapy/chemotherapy. Chemodynamic therapy (CDT) based on the Fenton reaction has been considered as a promising solution for the treatment of tumors. However, the limited therapeutic efficacy and lack of responsive release of Fenton agents still hinder the further application of CDT. To this end, we designed a disulfide bond (−S−S−) cross-linked polymer nanoparticles (poly(AA-co-DMA), PAD) to load FeOCl nanodots (FeOCl NDs) and doxorubicin (DOX) with the surface coating of bovine serum albumin (BSA) to prepare glutathione (GSH)/pH-responsive PAD-FeOCl/DOX@BSA nanoparticles (PFDB). In the tumor microenvironment (TME) with abundant GSH and acidic pH, the −S−S− bond in PFDB can be reduced and the linkage between the polymer chains is broken down, which facilitates the controlled release of FeOCl NDs and DOX. Both in vitro and in vivo experimental results showed that PFDB can serve as a GSH/pH-responsive nanoagent for the effective killing of 4T1 tumor cells by combined CDT/chemotherapy. This study provides a promising TME-responsive nanoagent with dual therapeutic modes for the effective treatment of tumors.

研究领域: 纳米技术 · 癌症研究 · 材料科学 · 药学
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Materials Today Nano · 2023 · IF 10.3

Multifunctional platinum-doped porous FeS2 nanoparticles for photothermal-enhanced photodynamic ferroptosis combination therapy

M. Feng,S. Xiao,Z. Liu,M. Li,X. Zhang,X. Chen,Y. Zhang,B. Chen,J. Liu

Explorations on ferroptosis combined with other tumor therapies have attracted much attention in recent years. To enhance the cargo-loaded capacity of the nanoparticles and integrate the ferroptosis as well as apoptosis, here, we reported the Pt-doped porous FeS 2 nanoparticles (Pt/pFeS 2 NPs) synthesized by the solvothermal method to realize the photothermal-enhanced photodynamic/ferroptosis antitumor combination therapy, with glucose oxidase (GOX)-loaded and 4T1 cell membrane-coated as the multifunctional Pt/pFeS 2 @ [email protected] nanovesicles (NVs). The porous structure provided more sites for Fenton reaction as well as photodynamic effect, which dramatically improve the level of reactive oxygen species . Additionally, the loaded GOX enhanced the generation of endogenous hydrogen peroxide and reduced the pH value of the tumor microenvironment, further promoting the Fenton reaction for ferroptosis. Moreover, Pt catalyzed the degradation of hydrogen peroxide to release oxygen, even facilitating the photodynamic therapy efficacy in the hypoxic tumor microenvironment. The rate of Fenton reaction and photocatalytic reaction were both significantly improved, leading to the acceleration of ferroptosis and photodynamic therapy with the increase of temperature under laser irradiation at 808 nm. Additionally, the in vivo antitumor therapy proved that Pt/pFeS 2 @ [email protected] NVs efficiently accumulated at tumor sites for photoacoustic imaging. To sum up, the multifunctional Pt/pFeS 2 @ [email protected] NVs could achieve photothermal-enhanced photodynamic/ferroptosis combination antitumor therapy and significantly inhibit the growth of 4T1 tumor without side-effects, shedding light on the promising application in photoacoustic image-guided tumor therapy system.

CAS / MDL: 9001-37-0
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 光声成像
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International Journal of Nanomedicine · 2024 · IF 6.6

Bioactive Nanoliposomes for Enhanced Sonodynamic-Triggered Disulfidptosis-Like Cancer Cell Death via Lipid Peroxidation

Hongwei Xiang,Bin Shen,Chunmei Zhang,Rui Li

Introduction Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.Methods Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.Results SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.Conclusion SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.

研究领域: 癌症治疗 · 纳米技术 · 细胞生物学 · 药学 · 生物医学工程
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MOLECULAR PHARMACEUTICS · 2024 · IF 4.5

Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes

Wenliang Sun,Chao Han,Ruirui Ge,Xiaotong Jiang,Yu Wang,Yingchao Han,Ning Wang,Yanzhi Song,Mingshi Yang,Guoliang Chen,Yihui Deng

Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand–receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.

研究领域: 药学 · 肿瘤学 · 药物递送系统 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2024 · IF 8.1

Thiacloprid-silica nano-delivery system enhances toxicity against Aphis gossypii and improves non-target biosafety

Xiaohui Yan,Yongpan Shan,Yajie Ma,Yanqin Wang,Changcai Wu,Xiangliang Ren,Xianpeng Song,Dan Wang,Hongyan Hu,Xiaoyan Ma,Yan Ma

Nanotechnology aligns with the requirements of sustainable development of agriculture, and nano-pesticides offer a promising approach to controlling agricultural pests and increasing productivity. Non-target predators also play a crucial role in pest controls and enhancing the efficacy of pesticide on target organisms. Reducing the toxicity of pesticides to non-target organisms is key to of coordinating chemical control and biological control methods. Therefore, it is essential to assess the toxicity of nano-pesticides on non-target predators. In this study, a carbon dots-doped mesoporous silica nano-delivery system (Thi@CD-MSN) was successfully developed using CD-MSN as carrier material and thiacloprid (Thi) as a model pesticide. The results demonstrated that the synthesized Thi@CD-MSN exhibited a relatively high loading efficiency (33.58%). Laboratory bioassay experiments revealed that Thi@CD-MSN demonstrated effective insecticidal activity (LC 50  = 21.67 mg/L) in controlling Aphis gossypii Glover. Besides, the acute toxicity of Thi@CD-MSN on Chrysoperla pallens larvae was significantly lower than that of Thi, as was its toxicity to 4T1 cells. These findings suggest that CD-MSN can serve as an ecological safety carrier for pesticide delivery, improving the effective utilization of Thi while reducing the risks to non-target predators. These results are essential for comprehending the effects of nano-pesticides on non-target predators, providing informative data for implementing biological and chemical control strategies. It strengthens the safety evaluation of nano-pesticides.

CAS / MDL: 141-78-6 57-09-0 78-10-4
研究领域: 农业科学 · 纳米技术 · 害虫管理 · 毒理学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Mesoporous platinum@copper selenide-based NIR-II photothermal agents with photothermal conversion efficiency over 80% for photoacoustic imaging and targeted cancer therapy

Jinzhe Liang,Yanting Yang,Yanni Luo,Lixian Huang,Shulin Zhao

Elevating photothermal conversion efficiency (PCE) is the key to enhance curative efficacy during photothermal therapy. Nevertheless, current functionalized or synthetic methods for preparing photothermal agents with high PCE are too complicated, greatly hindering the development of photothermal therapy. In this study, we developed a tumor-targeting flower-like nanocomposite termed mesoporous platinum nanoparticles@Cu 2- x Se-AS1411 (MPNPs@Cu 2- x Se-AS1411, denoted as MPCSA) with remarkable PCE for high-resolution photoacoustic (PA) imaging guided photothermal/chemodynamic therapy for tumor ablation. We discovered that MPNPs served as carriers for delivering PA contrast agents. Cu 2- x Se nanosheets emerged as promising near-infrared-II (NIR-II) PA imaging and photothermal/chemodynamic therapy agents owing to their strong localized surface plasmon resonance property in the NIR-II region. The amine-modified AS1411 aptamer, which is connected to the surface of the flower-like MPNPs@Cu 2- x Se can target the nucleolar protein on the surface of 4T1 cells, achieving the accumulation of MPCSA at the tumor site in mice. Notably, these MPCSA nano-flowers exhibited an excellent PCE up to 82.33 % under 1064 nm laser irradiation, resulting in highly efficient cancer cell ablation and greatly hindering in vivo tumor growth. This study has paved the way for imaging-guided accurate cancer diagnosis and targeted cancer therapy.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 癌症研究 · 诊疗学
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