MATERIALS & DESIGN
·
2025
·
IF 7.9
Xiuhua Lin,Suhua Jiang,Siting Zhang,Huaqin Zhang,Xin Lin,Jiaping Lin,Zhizong Shen
Owing to the heat resistance of heat shock proteins that trigger cellular antioxidants like glutathione (GSH), it is challenging to simultaneously inhibit the spread and metastasis of tumor nodules and prevent tumor recurrence using conventional photothermal therapy (PTT). In this research, for incorporation of PTT and GSH depletion, we utilized mesoporous polydopamine nanospheres doped with GSH-responsive tetrasulfide bonds (referred to as gMPDA) for the synergistic suppression of lung cancer cells. By incorporating Arg-Gly-Asp (RGD) peptides onto the surface (forming gMPDA-RGD), the stability and tumor-targeting specificity of this biodegradable nanoplatforms were markedly improved. In vitro studies testified that these innovative nanotherapeutics displayed an impressive photothermal conversion efficiency (η = 52.33 %) and efficient consumption of intracellular GSH, leading to the collapse of the PDA based nanoframe. Notably, the disruption of redox balance post-808 nm laser irradiation led to effective PTT and reactive oxygen species (ROS) production. Importantly, gMPDA-RGD manifested a strong tumor-targeting ability in lung tumor-bearing Balb/C mice under fluorescent imaging. The synergistic treatments led to complete elimination of tumor cells when exposed to 808 nm laser irradiation. This study underscored the potential of gMPDA-RGD as a potent nanomedicine for the synergistic therapy of PTT and GSH depletion in clinical malignant tumor.
✓ 已验证
产品关联
DOI
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Lidan Hu,Jiaying Ma,Xiaojie Wei,Yongzhen Li,Suhua Jiang,Xiaoxuan Ji,Fukai Zhu,Huaxin Tan,Peiyuan Wang
Breast cancer, as the common malignant carcinoma in women, seriously reduces the life quality and increases mortality of female worldwide. Fortunately, insufficient chemotherapy with external photothermal therapy could remarkably improve the therapeutic efficiency of breast cancer. In this work, we proposed a polydopamine (PDA) and tetrasulfide bond co-doped hollowed mesoporous silica nanospheres with Dox loading and surface hyaluronic acid coating for drug leakage avoidance (PhMSON@Dox-HA). After intravenously injected into tumor bearing-mice, this therapeutic agent could effectively target to the tumor site owing to the HA modification. The biocompatible property and GSH-induced decomposition capability endows the precise release of drugs in the cytoplasm of tumor cells. Meanwhile, PDA facilitated the efficient photothermal therapy under 808 nm laser irradiation. Therefore, the synergistic effect of chemo-photothermal therapy possessed most effective tumor eradication ability. Our work exploits the design approach of biocompatible and degradable drug delivery nanocarriers and sheds bright light on the chemotherapy and photothermal therapy combination for the malignant tumor elimination.
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
DOI
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2023
·Vol. 24
·期 1
·2200565
·
IF 4.6
Lele Hu,Chunli Song,Hongyi Li,Yao Gao,Jing Zhang,Ting Gao,Youhua Wei,Zhuoran Xu,Weiming Xue,Saipeng Huang,Huiyun Wen,Zigang Li,Jun Wu
Tumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double-sensitive composite hydrogel embedded with tetrasulfide-bridged mesoporous silica (4S-MSNs) is developed. The incorporation of 4S-MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S-MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S-MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence.
研究领域:
生物材料学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinyue Zhang,Ye He,Zhiqi Wang,Ying Zhang,Wen Guo,Shuai Li,Xinyu Wang,Yuling Mao,Siling Wang
To further develop intracellular delivery systems of macromolecular drugs, understanding the cracking mechanisms and drug release behaviors of environment-responsive carriers, as well as their intrinsic linkages, is essential for achieving personalized or diversified delivery of macromolecular drugs. Herein, we designed a class of degradable dendritic mesoporous nanoparticles (DDMSNs), utilizing very large cavities and tetrasulfide bonds in the skeleton to achieve high drug loading and release within tumor cells. To comprehensively understand and develop intracellular drug delivery systems, this study delved deeper into the delivery of tetrasulfide-bonded DDMSNs, including chemical reactions, cracking kinetics, and release kinetics. First, the drug release of the DDMSNs within the cytoplasm was closely related to the chemical reaction of tetrasulfide bonds. Thus, based on experiments, the oxidation–reduction mechanism of tetrasulfide-bonded DDMSNs was explained, and the relationship was elaborated between cracking and drug release of the DDMSNs with different sulfur contents. To further explore this relationship, the cracking behavior, drug-loading capacity and release capacity of the DDMSNs was investigated with the different sulfur contents in different simulated environments, and in MDA-MB-231 cancer cells. Inspired by the reaction kinetic calculations, we analyzed the cracking and drug release behavior of the DDMSNs, and ultimately achieved dual cracking secondary drug release of the carriers by controlling the content of sulfur elements. Here, we report improved biomedical materials for advanced, customized, and intentional intracellular delivery of therapeutic macromolecules, in which theoretical calculations and experimental components were combined to study the mechanism of drug release influenced by carrier cracking, providing essential guidance for designing advanced drug delivery systems through a chemical engineering method.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2023
·
IF 13.3
Jia Tan,Binbin Ding,Hao Chen,Qi Meng,Jing Li,Chunzheng Yang,Wenying Zhang,Xinyang Li,Di Han,Pan Zheng,Ping'an Ma,Jun Lin
Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure −Si−O−Si− framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.
研究领域:
纳米技术
·
免疫学
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Shiyi Zuo,Tian Liu,Lingxiao Li,Hezhen Xu,Jiayu Guo,Qing Wang,Yinxian Yang,Zhonggui He,Jin Sun,Bingjun Sun
Dimeric prodrug nanoassemblies (DPNAs) stand out as promising strategies for improving the efficiency and safety of chemotherapeutic drugs. The success of trisulfide bonds (-SSS-) in DPNAs makes polysulfide bonds a worthwhile focus. Here, we explore the comprehensive role of tetrasulfide bonds (-SSSS-) in constructing superior DPNAs. Compared to trisulfide and disulfide bonds, tetrasulfide bonds endow DPNAs with superlative self-assembly stability, prolonged blood circulation, and high tumor accumulation. Notably, the ultra-high reduction responsivity of tetrasulfide bonds make DPNAs a highly selective "tumor bomb" that can be ignited by endogenous reducing agents in tumor cells. Furthermore, we present an "add fuel to the flames" strategy to intensify the reductive stress at tumor sites by replenishing exogenous reducing agents, making considerable progress in selective tumor inhibition. This work elucidates the crucial role of tetrasulfide bonds in establishing intelligent DPNAs, alongside the combination methodology, propelling DPNAs to new heights in potent cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 45
·10822-10835
·
IF 7
Mingzhe Liu,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
The high glutathione (GSH) concentration and insufficient H2O2 content in tumor cells strongly constrict the efficacy of Fenton reaction-based chemodynamic therapy (CDT). Despite numerous efforts, it still remains a formidable challenge for achieving satisfactory efficacy using CDT alone. Herein, an intelligent tetrasulfide bond-bridged mesoporous organosilica-based nanoplatform that integrates GSH-depletion, H2S generation, self-supplied H2O2, co-delivery of doxorubicin (DOX) and Fenton reagent Fe2+ is presented for synergistic triple-enhanced CDT/chemotherapy/H2S therapy. Because the tetrasulfide bond is sensitive to GSH, the nanoplatform can effectively consume GSH, leading to ROS accumulation and H2S generation in the GSH-overexpressed tumor microenvironment. Meanwhile, tetrasulfide bond-induced GSH-depletion triggers the degradation of nanoparticles and the release of DOX and Fe2+. Immediately, Fe2+ catalyzes endogenous H2O2 to highly toxic hydroxyl radicals (˙OH) for CDT, and H2S induces mitochondria injury and causes energy deficiency. Of note, H2S can also decrease the decomposition of H2O2 to augment CDT by downregulating catalase. DOX elicits chemotherapy and promotes H2O2 production to provide a sufficient substrate for enhanced CDT. Importantly, the GSH depletion significantly weakens the scavenging effect on the produced ˙OH, guaranteeing the enhanced and highly efficient CDT. Based on the synergistic effect of triple-augmented CDT, H2S therapy and DOX-mediated chemotherapy, the treatment with this nanoplatform gives rise to a superior antitumor outcome.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Juan Li,Ziqing Gao,Ning Li,Ling Yao,Chao Liu,Che Xu,Xiaohui Ren,Aiqin Wang,Siqi Gao,Miao Wang,Xiang Gao,Kun Li,Jianfeng Wang
Background Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers.Methods In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections.Results In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities.Conclusion The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.
研究领域:
药学
·
纳米技术
·
眼科
·
毒理学
✓ 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）