INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Xinlong Wang,Huijie Zhou,Mengjiao Su,Yingxue Xu,Zhengxian Zhang,Haotian Peng,Huahui Zeng,Mingsan Miao,Xiangxiang Wu
The clinical use of chemotherapy alone has been restricted by its unsatisfactory curative effects and serious adverse effects. Chemotherapy combined with chemodynamic therapy (CDT) has recently emerged as an effective strategy for pancreatic cancer therapy. However, CDT needs to overcome insufficient intracellular iron ions, deficient endogenous hydrogen peroxide, and increased cellular antioxidant defense. Herein, we synthetized a novel organic iron-based polysaccharide nanocarrier (FDC) consisting of dextran, carboxymethyl chitosan and ferrocene. After encapsulating doxorubicin and palmitoyl ascorbate (VP), a charge reversal nanoparticle (VDF NPs) based on FDC was developed with high stability, allowing for enhanced tumor accumulation and prolonged retention in blood. VDF NPs are triggered to release drugs by the pH-responsive hydrolysis of Schiff-base group, and amplify intracellular hydrogen peroxide and iron levels to generate highly toxic reactive oxygen species (ROS) by Fenton reaction. In vitro and in vivo investigations showed that VDF NPs enhanced the synergistic antitumor efficacy through apoptosis mediated by both ROS and doxorubicin and the decrease of cellular antioxidant defense, and reduced doxorubicin-induced systemic toxicity via the nanoformulation and palmitoyl ascorbate. This work provided a promising strategy to develop organic iron-based polysaccharide nanocarrier with good biocompatibility and biodegradability for clinical applications.
研究领域:
肿瘤学
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纳米医学
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药剂学
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生物材料
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分子影像
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转化医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Small
·
2015
·Vol. 11
·期 21
·2543-2554
·
IF 8.368
Shi-Song Han,Ze-Yong Li,Jing-Yi Zhu,Kai Han,Zheng-Yang Zeng,Wei Hong,Wen-Xin Li,Hui-Zhen Jia,Yun Liu,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel dual-pH sensitive charge-reversal strategy is designed to deliver antitumor drugs targeting to tumor cells and to further promote the nuclei internalization by a stepwise response to the mildly acidic extracellular pH (≈6.5) of a tumor and endo/lysosome pH (≈5.0). Poly( l -lysine)- block –poly( l -leucine) diblock copolymer is synthesized and the lysine amino residues are amidated by 2,3-dimethylmaleic anhydride to form β-carboxylic amide, making the polypeptides self-assemble into negatively charged micelles. The amide can be hydrolyzed when exposed to the mildly acidic tumor extracellular environment, which makes the micelles switch to positively charged and they are then readily internalized by tumor cells. A nuclear targeting Tat peptide is further conjugated to the polypeptide via a click reaction. The Tat is amidated by succinyl chloride to mask its positive charge and cell-penetrating function and thus to inhibit nonspecific cellular uptake. After the nanoparticles are internalized into the more acidic intracellular endo/lysosomes, the Tat succinyl amide is hydrolyzed to reactivate the Tat nuclear targeting function, promoting nanoparticle delivery into cell nuclei. This polypeptide nanocarrier facilitates tumor targeting and nuclear delivery simultaneously by simply modifying the lysine amino residues of polylysine and Tat into two different pH-sensitive β-carboxylic amides.
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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产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY COMMUNICATIONS
·
2022
·
IF 3.428
Hao Guo,Songjie Fan,Jianhua Liu,Yumei Wang
The synergistic effect of leucovorin calcium (LVCa) on 5-fluorouracil (5-FU) has been widely confirmed, but as far as we know, there is no effective way to simultaneously deliver LVCa and 5-FU to tumor sites. In this paper we innovatively established a dual-pH sensitive drug release system based on ZIF-8 frameworks decorated with hyaluronic acid-LVCa bioconjugates linked with an acid-cleavable hydrazone bond to achieve the combinatorial delivery and on-demand drug release of 5-fluorouracil (5-FU) and leucovorin calcium (LVCa) at the acidic pH conditions of the tumor sites. The as-obtained HA-LVCa/5-FU@ZIF-8 nanoplatforms load 0.35 g of 5-FU and 0.048 g of LVCa per gram and exhibited high inhibiting colon cells growth performance in vitro.
研究领域:
药学
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癌症治疗
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INORGANIC CHEMISTRY
·
2025
·
IF 4.7
Zitian Zhuang,Yutong Gu,Wenjie Yang,Xianying Cao,Ling Zhang,Ke Jiang
Combination chemotherapy is a key strategy for improving cancer treatment efficacy and overcoming drug resistance, but it requires smart nanocarriers capable of codelivering multiple drugs and achieving precise release at the tumor site. Herein, we report a ZIF-90-based dual-drug delivery platform (NAR@ZIF-90-DOX) for synergistic cancer therapy. The natural product naringenin (NAR) was encapsulated within ZIF-90 pores via a “one-pot” method, while the chemotherapeutic drug doxorubicin (DOX) was covalently grafted onto the surface through a pH-sensitive Schiff base linkage. This dual-gated design leverages the acidic tumor microenvironment to trigger simultaneous ZIF-90 degradation and Schiff base cleavage. This enables the synchronous and targeted release of both drugs in 4T1 cells, leading to a significantly enhanced synergistic anticancer effect compared to single-drug administration. This work provides a strategy for designing multifunctional, intelligent Metal–Organic Frameworks (MOFs) nanoplatforms for combination chemotherapy.
研究领域:
纳米技术
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药学
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材料科学
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生物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 6
·
IF 13.117
Zecong Xiao,Zhenwei Su,Shisong Han,Jinsheng Huang,Liteng Lin,Xintao Shuai
The response to programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) blockade in cancer immunotherapy is limited because of multiple immune evasion mechanisms. Here, a previously unknown strategy is proposed to synergize the nuclear factor κB (NF-κB) inhibition and PD-1 blockade for antitumor immunotherapy. A dual pH-sensitive nanocarrier loading curcumin (CUR) and anti–PD-1 monoclonal antibody (aPD-1) may bind to circulating PD-1+ T cells and then follow their infiltration into the tumor. Furthermore, the nanodrug bound to PD-1+ T cells may be released in the tumor microenvironment, leaving aPD-1 to block PD-1 on T cells and generating a CUR-encapsulated cationic nanodrug that can be easily taken up by tumor cells/tumor associated macrophages (TAMs). Thus, not only the antitumor T cells mediate efficient CUR delivery to tumor but also the efficient CUR delivery promotes the tumor infiltration of antitumor T cells, thereby resulting in effective activation of antitumor immunity.
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2021
·Vol. 42
·期 5
·832-842
·
IF 6.15
Zhang Bing-bing,Chen Xiao-jie,Fan Xu-dong,Zhu Jing-jing,Wei Ying-hui,Zheng Hang-sheng,Zheng Hong-yue,Wang Bin-hui,Piao Ji-gang,Li Fan-zhu
Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pH e = 6.5, pH endo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
✓ 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）