Acta Biomaterialia
·
2021
·
IF 8.947
Lei Feng,Mengyao Chen,Ruihao Li,Lulu Zhou,Chunhui Wang,Pingting Ye,Xiaochun Hu,Jingxian Yang,Yanting Sun,Zhounan Zhu,Kang Fang,Keke Chai,Shuo Shi,Chunyan Dong
Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that can convert oxygen to highly cytotoxic singlet oxygen ( 1 O 2 ) through the co-localization of excitation light and photosensitizers . However, compromised by the hypoxic tumor microenvironment, the therapeutic efficacy of PDT is reduced seriously. Herein, to overcome tumor-associated hypoxia, and further achieve tumor-targeted synergistic chemotherapy/PDT/photothermal therapy (PTT), we have constructed a biodegradable oxygen-producing nanoplatform (named [email protected] ), which was composed of the porous metal-organic framework (PCN-224(Mn)), the poly (ADP-ribose) polymerase (PARP) inhibitor (Iniparib), and the polydopamine-modified hyaluronic acid (HA-PDA). Since HA can specifically bind to the overexpressed HA receptors (cluster determinant 44, CD44) on tumor cell, [email protected] prefers to accumulate at the tumor site once injected intravenously. Then iniparib can be released in tumor environment (TME), thereby dysfunctioning DNA damage repair and promoting cell apoptosis. At the same time, the chelating of Mn and tetrakis(4-carboxyphenyl) porphyrin (Mn-TCPP) can generate O 2 in situ by reacting with endogenous H 2 O 2 , relieving the hypoxic TME and achieving enhanced PDT. Moreover, owing to the high photothermal conversion efficiency of PDA, PTT can be driven by the 808 nm laser irradiation. As systematically demonstrated in vitro and in vivo , this nanotherapeutic approach enables the combined therapy with great inhibition on tumor. Overall, the as-prepared nanoplatform provide a promising strategy to overcome tumor-associated hypoxia, and shows great potential for combination tumor therapy. Statement of significance A delicately designed biodegradable oxygen-producing nanoplatform [email protected] is constructed to achieve combination therapy of solid tumors. Taking advantage of the active-targeting, PTT, enhanced PDT and PARPi, this nanotherapeutic approach successfully enables the combined chemo/photothermal/photodynamic therapy with great inhibition of solid tumors.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
·
药学科学
✓ 已验证
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
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癌症治疗
·
药物输送系统
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 9
·3453-3464
·
IF 6.843
Xiaofang Li,Wen Zhang,Jing Lin,Hao Wu,Yucen Yao,Jiayi Zhang,Chunrong Yang
The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment-responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)-disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) “antibody” to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a “membrane escape effect” and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.
研究领域:
肿瘤学
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药理学
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免疫疗法
·
纳米技术
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 41
·9492-9501
·
IF 5.344
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
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肿瘤治疗
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Mengyao Liu,Manfei Fu,Xiaoye Yang,Guoyong Jia,Xiaoqun Shi,Jianbo Ji,Xianghong Liu,Guangxi Zhai
Multidrug resistance (MDR) in tumor has long been considered a major factor in the failure of tumor chemotherapy. P-glycoprotein (P-gp)-mediated drug efflux plays a significant role in the MDR of tumor. Herein, paclitaxel (PTX) and P-gp inhibitor quercetin (QC) co-loaded and chondroitin sulfate (ChS)-coated mesoporous silica nanoparticles (MSNs) ( [email protected] ) were developed to reverse MDR in breast cancer and improve chemotherapy efficacy. The dual drug-loaded nanoparticles (NPs) showed a nanoscale size of ∼ 227.2 nm and redox-responsive drug release property. In vitro cell experiments showed that NPs exhibited CD44 receptor-mediated active targeting in MCF-7/ADR cells. The dual drug-loaded NPs had lower IC 50 value, higher apoptosis rate, obvious G2M phase arrest as well as stronger microtubule destruction in MCF-7/ADR cells compared to PTX-loaded NPs, suggesting that QC addition, significantly, improved the sensitivity of MCF-7/ADR cells to PTX. Further study found that QC-loaded NPs down-regulated the expression of P-gp. Notably, the dual drug-loaded NPs exhibited tumor-targeting ability, prolonged tumor retention time and effective anti-tumor effect without obvious toxicity to normal tissues in vivo . Taken together, our research provides a viable approach to overcome MDR in breast cancer.
研究领域:
药学
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纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
De-Sheng Liang,Jian Liu,Tao-Xing Peng,Hui Peng,Feng Guo,Hai-Jun Zhong
Cancer stem cells (CSCs) can resist conventional chemotherapy to lead to cancer recurrence. For complete eradication of cancers, an effective CSCs therapeutic strategy should be developed to combine with conventional chemotherapy. In this work, a novel vitamin E-based redox-sensitive salinomycin (SAL, an inhibitor for CSCs) prodrug nanoparticles (TS NPs) and hyaluronic acid (HA)-coated TS NPs (HTS NPs) were fabricated to deliver paclitaxel (PTX) for cancer-targeted and combined chemotherapy. Both TS and HTS prodrug NPs had mean diameter of about 200 nm with uniform size distribution, excellent drug loading capacity for PTX, and glutathione-triggered SAL and PTX release profiles. The HTS prodrug NPs had enhanced cellular uptake efficiency over TS NPs due to CD44 receptor-mediated endocytosis, hence exerting stronger potency of SAL upon CSCs-enriched mammospheres formation and G 0 /G 1 cell phase arresting. Cytotoxicity and 3D tumor spheroids assays demonstrated that both TS and HTS prodrug NPs themself can synergize with loaded PTX to maximize the chemotherapeutic effect. Obviously, the latter demonstrated a more potent anticancer efficacy due to improved intracellular drug delivery efficiency. These results suggested that the designed TS prodrug NPs, especially the coated HTS NPs can serve as an effective anti-CSCs strategy for cancer targeted and combination treatments.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 3
·477-495
·
IF 5.068
Sang Mangmang,Zhang Zhongtao,Liu Fulei,Hu Lejian,Li Lingchao,Chen Li,Feng Feng,Liu Wenyuan,Qu Wei
A novel multifunctional hyaluronic acid-decorated redox-responsive magnetic complex micelle (HA/CSO-SS-Hex/Fe3O4/PTX) based on a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and loaded with
paclitaxel (PTX) Fe3O4 nanoparticles is developed. HA is coated onto the surface of micelles via electrostatic absorption and acts as a targeting ligand for CD44 over expression in many tumor cells. A CSO-SS-Hex polymer micelle was used for PTX incorporation and GSH-triggered
intracellular release. The PTX in micelles was used to provide chemotherapy. Fe3O4 nanoparticles were used for magnetic targeting. The complex micelle showed enhanced antitumor efficiency and anti-cell-migration activity. The HA/CSO-SS-Hex/Fe3O4/PTX
micelle was stable under physiological conditions, while it was sensitive to release the loaded drug in the presence of 10 mM glutathione (GSH). The complex micelle showed enhanced cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated
internalization and redox-response drug release in tumor cells. Cell viability tests revealed that HA/CSO-SS-Hex/Fe3O4/PTX micelle displayed enhanced cytotoxicity against A549, B16F10 and HepG2 cell lines compared to non-targeted formulations of PTX. An anti-cell migration
assay was also performed. The result showed that although there was no significant difference in the anti-cell migration activities between the HA/CSO-SS-Hex/Fe3O4/PTX micelle and free PTX, the activities of HA/CSO-SS-Hex/Fe3O4/PTX were stronger
than non-targeted CSO-SS-Hex/Fe3O4/PTX micelles. Thus, the novel HA/CSO-SS-Hex/Fe3O4/PTX micelle is highly effective for targeted drug delivery and might have potential implications for the chemotherapy of primary tumors and their metastases.
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 NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-18
·
IF 10.435
Wang Xueqin,Xiong Tiandi,Cui Miao,Li Na,Li Qin,Zhu Li,Duan Shaofeng,Wang Yunlong,Guo Yuqi
Background Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer.Results HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis.Conclusion sTo sum up, these data provide a model for overcoming PTX resistance in ovarian cancer.Graphical Abstract
研究领域:
肿瘤学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yifan Li,Qiangwei Liang,Liyue Zhou,Yongjing Cao,Jiayu Yang,Juan Li,Jinxia Liu,Jiawei Bi,Yanhua Liu
The signaling cascade between nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) can be activated by proinflammatory M1 macrophages in rheumatoid arthritis (RA), which produces reactive oxygen species (ROS) and enhances M1 macrophage polarization, thus aggravating the development of RA. Therefore, an ROS-responsive artesunate prodrug micellar nanosystem for co-delivery of dexamethasone (DEX/HA-TK-ART micelles , abbreviated as DEX/HTA) was developed for synergistic inhibition of the HIF-1α/NF-κB cascade to regulate ROS scavenging and macrophage repolarization in RA combination therapy. DEX/HTA micelles displayed prolonged circulation in blood and efficiently co-delivered ART&DEX in the inflamed joints of adjuvant-induced arthritis (AIA) rats; moreover, they were specifically recognized and internalized into M1 macrophages through CD44 receptor-mediated endocytosis . ROS-responsive co-released ART&DEX then exerted a synergistic action to efficiently perform ROS scavenging and repolarization of M1 to M2 macrophages by inhibition of the HIF-1α/NF-κB cascade. The intravenous administration of DEX/HTA micelles into AIA rat models significantly alleviated inflammatory cell infiltration and repaired cartilage injury in the joint. Collectively, our study highlights the therapeutic potential of DEX/HTA micelles for treating RA through synergistic inhibition of the HIF-1α/NF-κB signaling cascade to regulate ROS scavenging and macrophage repolarization. Statement of significance An ROS-responsive artesunate (ART) prodrug micellar nanosystem for co-delivering dexamethasone (DEX), abbreviated as DEX/HA-TK-ART micelle, was developed for synergistic cascade regulation of the HIF-1α/NF-κB pathway on ROS scavenging and macrophage repolarization in combination therapy for rheumatoid arthritis. The well-designed nanosystem showed prolonged circulation in blood and superior ART&DEX accumulation in the inflamed joints of AIA rats; moreover, the micelles were specifically internalized into M1 macrophages and co-released ART&DEX, subsequently leading to inhibition of the HIF-1α/NF-κB pathway for ROS scavenging and macrophage repolarization, thus generating synergistic anti-inflammatory effects in RAW 264.7 cells and AIA rats. The HIF-1α/NF-κB cascade regulation on ROS scavenging and macrophage repolarization based on ART&DEX combination with smart nanotechnology could serve as a promising approach for rheumatoid arthritis therapy.
研究领域:
药理学
·
纳米技术
·
炎症
·
风湿病学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chenglong Wang,Yufeng He,Jun Tang,Jingying Mao,Xiaoya Liang,Maochang Xu,Zongquan Zhang,Ji Tian,Jun Jiang,Chunhong Li,Xiangyu Zhou
In the inflammatory microenvironment of atherosclerotic plaques, metabolic dysregulation of superoxide anion (O 2 − ) and hydrogen peroxide (H 2 O 2 ) leads to the activation of feedback mechanisms involving IL-1β, TNF-α, and MCP-1, which triggers inflammatory cascades between macrophages and vascular smooth muscle cells (VSMCs) in atherosclerosis (AS). To address this, a chondroitin sulfate (CS)-functionalized dual-targeted engineered nanozyme, CS-Lip/PB@Rap, was developed by encapsulating mesoporous Prussian blue nanoparticles (PBs) loaded with rapamycin (Rap) within CS-modified liposomes. CS functionalization endowed CS-Lip/PB@Rap with a specific targeting ability for CD44 receptors, thus enabling targeted delivery to inflammatory macrophages and VSMCs. Moreover, its enhanced multiple enzyme-like activities effectively modulated the imbalance of oxidative stress. The underlying mechanism of crosstalk regulation by these engineered nanozymes may inhibit the NF-κB pathway by restoring normal metabolism of O 2 − and H 2 O 2 , thereby blocking the TNF-α, IL-1β, and MCP-1 feedback loops between macrophages and VSMCs. This process reduced the production of inflammatory macrophages and inhibited the VSMC transformation from a contractile phenotype to a synthetic phenotype, preventing the formation of fibrous caps. Furthermore, the elimination of oxidative stress could decrease the production of oxygenized low-density lipoprotein (ox-LDL), which inhibited the formation of foam cells and alleviated the atherogenic progression.
研究领域:
纳米技术
·
药学
·
心血管疾病
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Min Yao,Mengjiao Ren,Wenxing Ding,Xiang Li,You Chen,Yang Chen,Xiuzhi Fu,Shulei Zheng,Ying Ma,Jiafeng Zou,Feng Gao
ABSTRACT Effective delivery of therapeutic drugs to colonic epithelial cells and macrophages is crucial for mitigating inflammation and repairing the intestinal barrier in inflammatory bowel disease (IBD). We developed a pH-triggered colonic targeted delivery nano system utilizing natural polymers, including chitosan (CS), hyaluronic acid (HA), and calcium alginate (ALG), encapsulating the active component shikonin (SK) to structure SK-loaded ALG/HA/CS delivery nano system (SK@LAS). The oral administration of SK@LAS specifically delivered SK in the colon via pH sensitivity and colonic targeting. SK@LAS was internalized by CD44 receptor-mediated endocytosis into macrophages. Furthermore, significant therapeutic effects of SK@LAS were observed in acute and chronic mouse colitis models, including reduced pro-inflammatory cytokines and mediators, increased expression of anti-inflammatory cytokines, and suppression of M1 polarization. Furthermore, SK@LAS upregulated the expression of tight junction proteins, thereby restoring intestinal barrier function. This colonic targeted delivery nano system exhibits promise as an oral drug delivery approach for the treatment of IBD.
研究领域:
药学
·
纳米技术
·
炎症
·
药物递送系统
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Wenhui Xie,Yilin Lu,Yilin Yuan,Lulu Xiao,Jiaqi Liu,Haofeng Song,Rongcheng Niu,Yanli Liu,Juntang Lin
Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (•OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant •OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物材料
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生物医学工程
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化疗
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药物递送系统
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肿瘤微环境研究
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光热治疗
·
铁死亡
✓ 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）