Biomedical Materials
·
2024
·Vol. 19
·期 2
·025024
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IF 3.9
Yibo Yang,Jia Zhang,Shihe Liu,Xin Zhang,Zhimin Bai,Shuai Wang,Kun Li,Ming Shi,Zhiwei Liu,Jidong Wang,Jian Li
The rapid, irreversible change of active Fe2+ to inactive Fe3+ after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here, β-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+ and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated as β-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+ and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2 by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.
研究领域:
生物医学工程
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肿瘤治疗学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Science China-Materials
·
2025
·
IF 7.4
Zhao Weidong,Zheng Mengfei,Chu Hongyu,Zhang Jingxuan,Wang Kun,Yang Chenguang,Shen Na,Tang Zhaohui
β-Lapachone (β-Lap) is a promising ortho -naphthoquinone drug for cancer treatment and has been in clinical trials. Its application is constrained by the low aqueous solubility, and severe side effects. Even prodrug designation is an effective approach to render it with tumor selectivity, it is limited by the lack of modifiable groups on β-Lap. Herein, a novel azo bond primary cleavage and carbon–carbon (C–C) bond secondary cleavage-based polymeric β-Lap prodrug (Azo-Lap NP) is designed, in which the self-immolated para -aminobenzyl linker is connected to poly( l -glutamic acid) (PGlu) via azo linkage and the responsive drug release of β-Lap against tumors can be achieved under high NAD(P)H:quinone oxidoreductase 1 (NQO1) expression and low pH environment in tumors. The effective covalent loading of β-Lap by Azo-Lap NPs permitted a high administration dose of β-Lap and enabled significant tumor retention time. Moreover, Azo-Lap NPs markedly reduced the side effects of β-Lap by avoiding hemolysis and the production of methemoglobin. The safety of Azo-Lap NPs administration is validated in the antitumor experiment of mice. In the 4T1 model, Azo-Lap NPs exhibited a markedly higher tumor suppression rate than β-Lap. This work provides an effective and safe polymeric prodrug for tumor selective delivery of β-Lap.
研究领域:
药物化学
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肿瘤学
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生物医学工程
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产品关联
DOI
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
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药剂学
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神经科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2024
·
IF 4.4
Hui-Zhen Yang,Jia-Jia Chen,Lan Zhang,Xiao-Li Tian,Rong Wang,Lin Pu,Xiao-Qi Yu,Ji Zhang
Nitric oxide (NO) / β-Lapachone (Lap) combined therapy by causing oxidative stress is an effective tumor therapy strategy. Herein, a dual-responsive lipid nanoparticles (LNPs) LSNO for NO / Lap co-delivery were constructed from the zinc-coordinated lipid ( DSNO(Zn) ) and the hydrophobic drug Lap in the presence of helper lipids (DOPE and DSPE-PEG 2000 ). The zinc-coordinated structure in LSNO might elevate the Zn 2+ content in tumor cells, contributing to antioxidant imbalance. The fluorescent assays proved the light-triggered NO release and fluorescent self-reporting abilities of LSNO . In addition, the LNPs had good drug release behavior under high concentration of GSH, indicating the NO / drug co-delivery capacity. In vitro antitumor assays showed that the NO / Lap combination treatment group could induce more significant tumor cell growth inhibition and cell apoptosis than individual NO or Lap treatment. The following mechanism studies revealed that NO / Lap combination treatment led to distinct oxidative stress by producing reactive oxygen species (ROS) and peroxynitrite anion (ONOO – ). On the other hand, the intracellular redox balance could be further disrupted by Lap-induced NADPH consumption and Zn 2+ / NO-induced reductase activities downregulation, thus promoting the degree of cell damage. Besides, it was also found that NO and Lap could directly damage nuclear DNA and induce mitochondrial dysfunction, thereby leading to caspase-3 activation and tumor cell death. These results proved that LSNO could serve as a promising multifunctional tumor therapy platform.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Fang Liu,Yaru Li,Yao Li,Zheng Wang,Xin Li,Yancheng Liu,Yanjun Zhao
The clinical translation of the anticancer drug β -lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe 3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways ( e.g ., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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细胞死亡机制
✓ 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
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癌症治疗
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Xuling Chen,Jianbo Ji,Ke Zhou,Xiaohui Fan,Lingbing Li,Wei Xu
Despite its high antitumor activity , the clinical application of chemotherapy is greatly impeded by lacking of specific accumulation and poor solubility. To address the above challenges, we designed a AS1411 aptamer modified nanoparticles based on molecular recognition of nucleobases . Firstly, a redox sensitive Paclitaxel-SS-Zidovudine (PZ) prodrug was synthesized. Then PZ/β-lapachone/AS1411/DSPE-PEG nanoparticles were prepared and AS1411 aptamer was connected through molecular recognition between the nucleoside analogue Zidovudine (ZDV) and the thymine on aptamer. DSPE-PEG (DP) was incorporated into nanoparticles to prolong the residence time of nanoparticles in the blood circulation . Furthermore, to realize the combination treatment, β-lapachone (LAP) has been incorporated into nanoparticles with high drug loading efficiency through the interaction of π-π stacking force and H-bonding between LAP and Paclitaxel (PTX). LAP can generate abundant exogenous reactive oxygen species (ROS) via the bioactivation of NAD(P)H: quinone oxidoreductase-1 (NQO1). Moreover, the connection of Zidovudine (ZDV) and AS1411 through molecular recognition of nucleobases further optimized the nanoparticles with high affinity to nucleolin which overexpressed on tumor cell membrane , thereby inducing the specific accumulation of nanoparticles in tumor sites. In vivo and in vitro studies showed that the obtained nanoparticles of PZ/LAP/AS1411/DP exhibited better tumor growth inhibition and lower systemic side effects. Herein, we have rationally conducted a novel self-codelivery system for effectively synergistic antitumor treatment.
研究领域:
药理学
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）