ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Tingting Luan,Lulu Cheng,Ju Cheng,Xiaoyun Zhang,Yufei Cao,Xiangdong Zhang,Haiyan Cui,Guanghui Zhao
The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced “sequential induced activation processes” for efficient tumor therapy by designing a new ROS-responsive drug release platform. β-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The β-lapachone released in the tumor cells induces a large amount of H2O2, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of H2O2. The activated NM leads to tumor cell apoptosis.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Yuxiang Dai,Yuanping Min,Lu Zhou,Longyang Cheng,Hongbin Ni,Yang Yang,Wendi Zhou
Glioblastoma (GBM) is a central nervous system cancer with high incidence and poor survival rates . Enhancing drug penetration of the blood-brain barrier (BBB) and targeting efficacy is crucial for improving treatment outcomes. In this study, we developed a redox-sensitive targeted nano-delivery system (HCA-A2) for temozolomide (TMZ) and β-lapachone (β-Lapa). This system used hyaluronic acid (HA) as the hydrophilic group, arachidonic acid (CA) as the hydrophobic group, and angiopep-2 (A2) as the targeting group. Control systems included non-redox sensitive (HDA-A2) and non-targeting (HCA) versions. In vitro, HCA-TMZ-Lapa micelles released 100 % of their payload in a simulated tumor microenvironment within 24 h, compared to 43.97 % under normal conditions. HCA-A2 micelles, internalized via clathrin-mediated endocytosis, showed stronger cytotoxicity and better BBB penetration and cellular uptake than controls. In vivo studies demonstrated superior tumor growth inhibition with HCA-A2 micelles, indicating their potential for GBM treatment.
研究领域:
肿瘤学
·
药剂学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Zhao Pan,Gong Liyang,Chang Le,Du Huiping,Geng Meijuan,Meng Siyu,Dai Liangliang
Chemodynamic therapy (CDT) is seriously limited by the inadequacy of exogenous catalytic ions and endogenous H 2 O 2 in tumors. Herein, a multifunction nano-bomb integrated with calcium peroxide (CaO 2 ) and β-lapachone as donors of H 2 O 2 and GSH-sensitive Fe-based coordination polymer as provider of catalytic ions was constructed for dual cascade-amplified tumor CDT. This hyaluronic acid (HA)-modified nano-bomb could be specially endocytosed by breast cancer cells through a targeting pathway, degraded and released cargoes in response to the GSH-rich cytoplasm. Furthermore, the released CaO 2 and β-lapachone could significantly self-generated sufficient H 2 O 2 , which could dual-cascade amplify CDT and induce severe oxidative to tumors via cooperating with the delivered iron ions from nano-bombs. Moreover, the unloaded iron and calcium ions could further accelerate tumor damage by overloading Ca 2+ and ferroptosis, as accompanied by good magnetic resonance imaging (MRI). In vitro and in vivo studies collectively reveal that this nano-bomb not only self-initiates double cascade-amplified CDT via self-generation of H 2 O 2 , but also efficiently activates ferroptosis and initiates Ca 2+ overloading, consequently significantly tumor growth suppression. This study offers a novel tumor-initiated nano-bomb for dual cascade-amplified CDT and bioimaging with activated ferroptosis and self-supplying H 2 O 2 .
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Xiaodi Gong,Jing Wang,Linlin Yang,Lijuan Li,Xiaoyan Gao,Xiao Sun,Jingfeng Bai,Jichang Liu,Xin Pu,Yudong Wang
Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H 2 O 2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H 2 O 2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1) high catalase (CAT) low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes β-Lap to produce excess H 2 O 2 and initiate oxidative stress, which selectively suppress NQO1 high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1 high EC cells from β-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H 2 O 2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1 high EC.
研究领域:
肿瘤学
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药学
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生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Wenting Li,Jihui Zhou,Yangyang Zhang,Shikai Liu,Rumin Li,Shili Gai,He Ding,Lei Zhong,Piaoping Yang
Photothermal-enhanced chemodynamic therapy (CDT) based on the Fenton reaction has been widely studied as a safe, tumor-specific, and highly effective nanomedicine therapy. Herein, a collective hyperthermia-facilitated glutathione (GSH) inhibition strategy for boosted oxidative stress treatment was presented using mesoporous Prussian blue (MPB NPs) as a multifunctional carrier and loading β-lapachone (Lap) as an oxidative mediator. A phase transfer catalyst (lauric acid, La) was co-packed for preventing drug leakage and achieving temperature-controlled drug release. After biocompatible decoration by external encapsulation with polyethylene glycol (PEG), the MPB-Lap/La@PEG nanocatalysts (Mlalp NCs) were rationally constructed. Upon 808 nm light irradiation, the Mlalp NCs showed a good photothermal effect with temperature increases for directly damaging tumor cells and accelerating the release of Lap. Significantly, the expression of NAD(P)H: quinone oxidoreductase-1 (NQO1) in cells could increase and generate more hydrogen peroxide (H 2 O 2 ) with Lap and reduce the level of GSH concurrently, forming a hyperthermia-facilitated glutathione inhibition strategy. Most importantly, the hyperthermia also accelerated the Fenton reaction rate, resulting in an enhanced CDT effect. In addition, the Mlalp NCs also equipped with excellent T 1 -weighted magnetic resonance imaging properties. To sum up, this work displays a collective hyperthermia-facilitated glutathione inhibition strategy for boosted oxidative stress treatment.
研究领域:
纳米医学
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Wenying Zhang,Meifang Wang,Bin Liu,Meng Yuan,Zhuang Yang,Jia Tan,Ping'an Ma,Jun Lin
The tumor thermotolerance owing to the overexpression of heat shock proteins (HSPs) is the critical challenge in practical application of mild-temperature photothermal therapy (MPTT). Reactive oxygen species (ROS) can not only serve as a powerful weapon to kill cancer cells, but also a regulator to inhibit HSPs, thus improving the thermal sensitivity of tumors. Herein, a multi-model ROS regulation nano-platform based on TCLP nanocomposites consisting of polyacrylic acid encapsulated, chloroperoxidase (CPO) and β-Lapachone (β-Lap) loaded black mesoporous titanium (H-TiO 2 ) has been constructed for the ROS-enhanced MPTT. In this nano-platform, the H-TiO 2 acts as the NIR-Ⅱ light triggered photothermal agent and photosensitizer to contribute to deep tissue MPTT and PDT, the β-Lap acts as a H 2 O 2 amplifier to improve the 1 O 2 production of CPO. The abundant ROS from TCLP NPs can limit the activity as well as the expression of HSPs, ultimately improving the antitumor efficacy of MPTT. Finally, excellent synergistic tumor inhibition based on TCLP NPs has been reached both in vitro and in vivo. This multi- model ROS enhanced MPTT nano-platform with low toxic side effects offers a promising strategy and enlightenments the clinical application of MPTT.
研究领域:
癌症治疗
·
纳米技术
·
光热治疗
·
活性氧调控
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-22
·
IF 17.694
Wang Xuan,Liu Yingqi,Xue Chencheng,Hu Yan,Zhao Yuanyuan,Cai Kaiyong,Li Menghuan,Luo Zhong
cGAS-STING pathway is a key DNA-sensing machinery and emerges as a promising target to overcome the immunoresistance of solid tumors. Here we describe a bovine serum albumin (BSA)/ferritin-based nanoagonist incorporating manganese (II) ions and β-lapachone, which cooperatively activates cGAS-STING signaling in dendritic cells (DCs) to elicit robust adaptive antitumor immunity. Mn 2+ -anchored mannose-modified BSAs and β-lapachone-loaded ferritins are crosslinked to afford bioresponsive protein nanoassemblies, which dissociate into monodispersive protein units in acidic perivascular tumor microenvironment (TME), thus enabling enhanced tumor penetration and spatiotemporally controlled Mn 2+ and β-lapachone delivery to DCs and tumor cells, respectively. β-lapachone causes immunogenic tumor cell apoptosis and releases abundant dsDNA into TME, while Mn 2+ enhances the sensitivity of cGAS to dsDNA and augments STING signaling to trigger downstream immunostimulatory signals. The cGAS-STING nanoagonist enhances the tumor-specific T cell-mediated immune response against poorly immunogenic solid tumors in vivo, offering a robust approach for immunotherapy in the clinics.
研究领域:
免疫学
·
肿瘤学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Weijuan Zou,Longchen Wang,Junnian Hao,Lixian Jiang,Wenxian Du,Tao Ying,Xiaojun Cai,Haitao Ran,Jianrong Wu,Yuanyi Zheng
Insufficient concentrations of intracellular substrates such as hypoxia and H 2 O 2 considerably reduce the effectiveness of reactive oxygen species (ROS)-associated cancer therapy. Modulating the tumor microenvironment (TME) for augmenting efficacy has become a promising strategy. Herein, a phase-change cascaded nanomedicine (Lap-IrO x @PCM) was constructed via co-encapsulation of iridium oxide nanozyme (IrO x ) and β-lapachone (Lap) by using thermal-responsive phase-change materials (PCMs). After photothermal activation, the protective PCM layer was melted, causing the rapid release of IrO x and Lap. Simultaneously, the peroxidase-like nanozyme IrO x reacted with endogenous H 2 O 2 to liberate highly toxic hydroxyl radicals (•OH) for inducing tumor cell death. Meanwhile, IrO x as another glutathione peroxidase nanozyme also consumed glutathione (GSH) to protect ROS from scavenging. Importantly, the released Lap efficiently generated H 2 O 2 for facilitating the catalytic efficacy of IrO x and provoke the cleavage of heat shock protein 90 (Hsp90) for overcoming tumor heat tolerance in photothermal therapy (PTT). As systematically demonstrated both in vitro and in vivo , this well-defined system achieved a superior antitumor effect via mild photothermal-enhanced nanocatalytic therapy. Our findings have provided the proof of concept of the phase change-mediated, in vivo catalytic activity of nanozymes that can be customized for intensive, TME-mediated, self-enhanced nanocatalytic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 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）