Applied Materials Today
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2021
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IF 10.041
Kai Wang,Shuaishuai Ding,Lijuan Zeng,Jingrong Zhou,Yuhua Cao,Jiaqian Wu,Lu Lu,Xiu-wu Bian,Gan Tian
Hypoxia-acquired radioresitance is considered to be a major factor responsible for the clinical failure of radiotherapy. Carbonic anhydrase IX (CA IX), a hypoxia-induced cell-surface enzyme involved in pH regulation of hypoxic solid tumors, has been acknowledged as a desirable target for cancer therapy. Herein, we developed a dual exogenous/endogenous CA IX inhibition strategy using core/satellite-like metal-organic framework (UiO-66)/gold nanoparticles (Au NPs) nanohybrids as a therapeutic platform for hypoxia-relief enhanced RT of triple negative breast cancer. The UiO-66 matrix supported the Au NPs generation in situ and would decompose inside tumor cells by the high-concentration phosphates to release p -phthalic acid (PTA), a original building skeleton of the UiO-66 matrix, to inhibit CA IX, while the decorated Au NPs served as radiosensitizers to potentiate the sensitivity of tumor cells to X-ray and yet provided active sites for CA IX antisense oligonucleotide (ASO) loading via formation of stable Au-S bond to knockdown CA IX. The dual inhibitory manner, exogenous inhibition from PTA and endogenous inhibition from CA IX ASO, largely alleviated the hypoxia-induced resistance and synergized with Au NPs-mediated radiosensitization to afford super therapeutic outcome in vitro and in vivo , supporting the feasibility of our synergistic RT strategy in hypoxic tumor management.
研究领域:
癌症治疗
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纳米技术
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放射生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 30
·期 6
·1908365
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IF 15.621
Xiaoyan Chen,Huilin Zhang,Meng Zhang,Peiran Zhao,Ruixue Song,Teng Gong,Yanyan Liu,Xinhong He,Kuaile Zhao,Wenbo Bu
Chemodynamic therapy (CDT) by introducing the Fenton-/Fenton-like reaction in an acidic and H 2 O 2 environment for toxic hydroxyl radical (•OH) generation, is a newly developed tumor-selective therapeutic. However, tumor acidosis, characterized by extracellular acidity (pH e ≈ 6.5) and intracellular alkalinity (pH i ≈ 7.2), undoubtedly confers a large chemical barrier for effective implementation of intracellular CDT and thus limits its functional activity and therapeutic efficacy. Here, the unique amorphous iron nanoparticles (AFeNPs) loaded with carbonic anhydrase IX inhibitor (CAI) are constructed to re-establish tumor acidosis with decreased pH i and increased pH e via inhibiting the over-expressed CA IX in cancer cells by CAI for self-enhanced CDT. The suppression of CA IX leads to H + accumulation in cells that could accelerate the AFeNPs-based Fenton reaction to drastically exacerbate oxidative stress in cells and subsequently induce cell death; meanwhile, the inhibition of H + formation outside cells efficiently represses the potential of tumor invasion and metastasis owing to the insufficient acidic ions for degradation of tumor extracellular matrix. Re-established tumor acidosis not only assists in the optimization of CDT, but also presents an opportunity for the development of new antitumor methods that are more tumor-acidity specific.
研究领域:
纳米医学
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癌症治疗
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2019
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IF 13.903
Tengchuang Ma,Yunduo Liu,Qiong Wu,Lifang Luo,Yali Cui,Xinghua Wang,Xiuwei Chen,Longfei Tan,Xianwei Meng
The development of multifunctional nanoscale radiosensitizers has attracted a tremendous amount of attention, which can enhance the radiosensitization of tumor tissues and reduce unnecessary damage to the surrounding organs. However, the persistent hypoxia environment within the tumor limits their applications in radiotherapy. In this paper, a stable nanocomposite was engineered to overcome the hypoxia properties by using 1,4-benzenedicarboxylic acid produced from a Zr-MOF as a carbonic anhydrase IX (CA IX) inhibitor and quercetin (QU) as a radiosensitizer. QU was encapsulated into the Zr-MOF structure to achieve a synergetic dual sensitization therapy. Zr-MOF-QU exhibits an excellent potential of radiotherapy sensitization characteristics in vitro and in vivo from the γ-H2AX immunofluorescence staining and colony assays. The mechanisms of alleviating hypoxia-induced resistance and sensitizing tumor tissues to improve cell apoptosis from radiation were found to suppress CA IX expressions by the decomposition product from Zr-MOF and boost the sensitivity by QU in radiation therapy. Moreover, there was no significant systemic toxicity during the treatment, and the therapeutic outcome was assessed in animal models. Therefore, our results demonstrate a promising cancer treatment approach in the radiation field.
研究领域:
癌症治疗
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纳米技术
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放射生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2018
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IF 6.735
Wei Zhu,Li Zhang,Zhe Yang,Pei Liu,Jing Wang,Jinguo Cao,Aiguo Shen,Zushun Xu,Jing Wang
Though imaging guided photodynamic therapy (PDT) has emerged as a promising cancer therapy, how to enhance the PDT efficiency is still a research hotpot due to the tumor hypoxia and insufficient dosage of photosensitizers in the tumor site. Herein, a multifunctional theranostic nanoplatform was rationally constructed by nanoscale metal organic frameworks (NMOFs), bovine serum albumin (BSA), sulfadiazines (SDs), and MnO 2 . Porphyrin as organic ligands involved in the formation of NMOFs, which could allow more photosensitizers in one system. BSA as ideal carrier endows the nanoplatform with low toxicity and long circulation. SDs was introduced to provide actively targeting for the over-expressed carbonic anhydrase IX (CA IX) in tumor cells. More importantly, this nanoplatform can overcome the hypoxic microenvironment via down-regulating CA IX and catalyzing H 2 O 2 to generate O 2 , resulting in significantly enhanced PDT effect, which was demonstrated by the photocytotoxicity against 4T1 cells and the decreased tumor volume. In addition, in vitro/vivo T 1 -weighted MRI results showed that the nanoplatform could be served as positive MRI contrast agent with a higher longitudinal relaxivity value (r 1 ) at 6.09 mM −1 s −1 than that of clinical clinical contrast agent (Gd-DTPA, r 1 = 4.33 mM −1 s −1 ). Such theranostic nanoplatform integrates multifunctional contents into one system and thereby provides a new strategy for targeted tumor therapy.
研究领域:
癌症治疗
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纳米技术
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医学成像
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-16
·
IF 9.429
Liu Jie,Hu Xiaochun,Feng Lei,Lin Yun,Liang Shujing,Zhu Zhounan,Shi Shuo,Dong Chunyan
Background Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4‐(2‐aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment. Results ABS and PEG-NH 2 were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis. Conclusion Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility. Graphical Abstract
研究领域:
癌症生物学
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Nan Wang,Mingjian Zhu,Shengfei Yang,Jiahe Wu,Manning Zhu,Lan Ma,Xunqi Zhang,Donghang Xu,Bo Zhang,Jianqing Gao,Nengming Lin
Chemoimmunotherapy holds promise in enhancing tumor immunogenicity via inducing immunogenic cell death (ICD), while still fails to elicit robust anti-tumor immunity mainly due to the low drug delivery efficiency and the immunosuppression in tumor microenvironment (TME). Herein, an engineered pluripotential biomimetic nanovehicle favorable for tumor-targeted drug delivery and TME modulation is developed by simply incorporating tumor cell membrane into a carbonic anhydrase IX inhibitor (CAI) chemically-modified liposome. Profiting from plasma membrane-mediated homotypic adhesion and CAI-mediated active targeting, ADM exhibits high affinity for autologous tumors and can improve the accumulation of drugs into the tumor tissues. Importantly, ADM can metabolically inhibit extracellular H + production to remodel the acidic immunosuppressive TME and serve as a tumor antigen pool, potentiating anti-tumor immune response. As a result, ADM facilitates tumor-targeted delivery of doxorubicin (DOX), and synergizes DOX-mediated ICD induction with a synergistic TME modulating feat, thus reinforcing cancer chemoimmunotherapy. The rationally designed pluripotent biomimetic nanovehicle orchestrates precision drug delivery with simultaneous immunomodulation, furnishing a compendious yet powerful platform for augmenting anti-tumor immunity.
研究领域:
纳米医学
·
免疫治疗
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癌症生物学
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药物递送
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生物工程
✓ 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）