Pharmaceutics
·
2023
·Vol. 15
·期 10
·2443
·
IF 5.4
Xinqiang Liang,Mekhrdod S. Kurboniyon,Yuanhan Zou,Kezong Luo,Shuhong Fang,Pengle Xia,Shufang Ning,Litu Zhang,Chen Wang
Traditional treatment methods for tumors are inefficient and have severe side effects. At present, new therapeutic methods such as phototherapy, chemodynamic therapy, and gasodynamic therapy have been innovatively developed. High concentrations of hydrogen sulfide (H2S) gas exhibit cancer-suppressive effects. Herein, a Prussian blue-loaded tetra-sulfide modified dendritic mesoporous organosilica (PB@DMOS) was rationally constructed with glutathione (GSH)-triggered/photothermal-enhanced H2S signaling molecule release properties for gas therapy. The as-synthesized nanoplatform confined PB nanoparticles in the mesoporous structure of organosilica silica due to electrostatic adsorption. In the case of a GSH overexpressed tumor microenvironment, H2S gas was controllably released. And the temperature increases due to the photothermal effects of PB nanoparticles, further enhancing H2S release. At the same time, PB nanoparticles with excellent hydrogen peroxide catalytic performance also amplified the efficiency of tumor therapy. Thus, a collective nanoplatform with gas therapy/photothermal therapy/catalytic therapy functionalities shows potential promise in terms of efficient tumor therapy.Keywords:gas therapy;H2S;GSH-triggered;Prussian blue;dendritic mesoporous organosilica
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 7
·2951-2960
·
IF 5.251
Tiangang Yang,Dechao Niu,Jianzhuang Chen,Jianping He,Shaobo Yang,Xiaobo Jia,Jina Hao,Wenru Zhao,Yongsheng Li
Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.
研究领域:
纳米技术
·
生物材料
·
癌症治疗
·
医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 13
·期 1
·160-172
·
IF 8.183
Zhang Amin,Zhang Qian,Alfranca Gabriel,Pan Shaojun,Huang Zhicheng,Cheng Jin,Ma Qiang,Song Jie,Pan Yunxiang,Ni Jian,Ma Lijun,Cui Daxiang
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment. In this regard, we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic. The multifunctional probes consisted of a gold/platinum star-shaped core (Au/Pt star) conjugated with a GSH-sensitive disulfide bond (S–S), a targeting ligand (rHSA-FA), a near-infrared fluorophore (IR780) and glucose oxidase (GO x ). When systemically administered in a xenografted murine model, the probes specifically targeted the tumor sites. As the disulfide linker was cleaved by intracellular GSH, the IR780 molecules could be released for photo-thermal therapy & photodynamic therapy (PTT&PDT) and imaging. Subsequently, the Pt nanolayer of the Au/Pt star and the GO x formed a sequential catalytic system: GO x effectively catalyzed intracellular glucose by consuming oxygen to generate H 2 O 2 and enhance the local acidity, and the Pt layer exhibited peroxidase-like property to catalyze H 2 O 2 producing toxic ·OH for tumor oxidative damage. Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release, real-time imaging ability, and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features, which provides a potential strategy for effective tumor theragnostic.
研究领域:
癌症治疗
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生物化学
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纳米医学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 12
·2483-2494
·
IF 5.344
Kun Zeng,Li Ma,Wenxiu Yang,Shan Lei,Mozhen Wang,Yezi You,Yu Zhao,Xuewu Ge
Finding and exploiting safe and high-efficiency gene carriers have always been critical tasks for gene therapy. In this work, novel GSH-triggered degradable organosilica nanoparticles grafted with guanidinated-fluorinated α-polylysine (o-SiNP-GF) are prepared to be studied as gene carriers. The organosilica matrix of o-SiNP-GF is synthesized through the hydrolysis and condensation of 1,2-bis(triethoxysilyl)ethane (BTSE) and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTSPTS). The o-SiNP-GF nanoparticles have a size of about 20 nm. They possess a positive zeta potential of 42 mV in PBS (pH 7.4) and can be disintegrated in the presence of GSH. The cytotoxicity and DNA-binding ability of o-SiNP-GF, as well as in vitro gene transfection performance of DNA/o-SiNP-GF complexes, have been investigated using enhanced green fluorescent protein plasmid (pEGFP) as the DNA model. MTT assay shows that the cytotoxicity of o-SiNP-GF is very low even at a concentration up to 800 μg mL−1. The o-SiNP-GF nanoparticles can effectively bind to pEGFP through a complex coacervation method. The in vitro transfection efficiency of pEGFP/o-SiNP-GF complexes in 293T cells is up to 94.7% at the N/P ratio of 10, much higher than that of pEGFP/PEI complexes. Luciferase gene and fibroblast growth factor (FGF2) gene are also used as the DNA models to study the in vivo gene transfection performance of the o-SiNP-GF carrier by bioluminescence imaging and the evaluation of the healing rate of a mouse wound, respectively. Compared with naked DNA and DNA/PEI complexes, DNA/o-SiNP-GF complexes show much higher in vivo transfection efficiency. This work not only provides a way to prepare novel GSH-triggered degradable organosilica nanoparticles of size less than 50 nm, but also proves that the modification of guanidinated-fluorinated α-polylysine is an effective method to improve the efficiency of gene carriers.
研究领域:
基因治疗
·
纳米技术
·
材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Tingjie Yin,Jiyong Liu,Zekai Zhao,Lihui Dong,Han Cai,Lifang Yin,Jianping Zhou,Meirong Huo
Co-delivery systems capable of transporting hydrophobic chemotherapeutics and hydrophilic siRNA to the same cell population with simultaneous burst release of both drugs to maximize synergistic anticancer efficacy remains elusive. In this light, a multifunctional nanoparticle (HA-PSR) consisting of a redox-sensitive core and detachable crosslinked hyaluronic acid (HA) shell was developed. Octyl modified PEI containing disulfide linkages (PSR) were synthesized as the core materials for co-encapsulation of chemotherapeutics and siRNA, while a HAase-sensitive thiolated HA (HA-SH) was collaboratively assembled to the anionic shell for CD44-mediated active targeting along with enhanced and detachable protection for drug loaded inner cores. Resultantly, HA de-protected redox-sensitive inner cores achieved co-burst release of both cargoes when triggered by glutathione (GSH) rich environments in cytoplasm. Results of in-vivo and in-vitro testing indicated successful co-encapsulation of hydrophobic drugs and hydrophilic siRNA with adjustable ratios. Selective delivery to CD44 overexpressing tumors was achieved through passive and active targeting, followed by HAase-triggered HA de-shielding and GSH-triggered burst release of both cargos. Rapid intracellular trafficking maximized synergistic cytotoxicities of chemotherapeutics and siRNA for remarkable tumor inhibition in a xenograft animal tumor model. Consequently, the HA-PSR nanoparticle holds great potential for combined chemotherapeutics/siRNA treatment in cancer with maximized synergistic antitumor efficacy.
研究领域:
纳米技术
·
癌症研究
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药学科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2020
·Vol. 63
·期 7
·924-935
·
IF 6.356
Yuan Haifeng,Zhao Yan,Yang Chan,Zhang Cheng,Yang Yue,Meng Hongmin,Huan Shuangyan,Song Guosheng,Zhang Xiaobing
For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species (ROS) based cancer therapeutic strategy ( e.g. , chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug (6-thioguanine) as ligand copper ions, we achieve a high drug loading rate (60.1%) and 100% of utilization of metal-drug coordination nanoplatform (Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione (GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T 1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging (MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo .
研究领域:
癌症治疗
·
药物递送系统
·
纳米技术
·
磁共振成像
·
生物医学工程
·
化学生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）