International Journal of Nanomedicine
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2024
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IF 6.6
Longjiang Zhou,Haitao Xiang,Susu Liu,Honglin Chen,Yuanwei Yang,Jianyong Zhang,Wei Cai
Purpose Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored.Methods AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively.Results In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas.Conclusion This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.
研究领域:
癌症研究
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纳米技术
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诊疗一体化
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生物医学工程
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医学影像
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
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2025
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IF 9.6
Bei Liu,Huijuan Duan,Lirong Sun,Zechao Liu,Zhaogang Sun,Hongqian Chu
The use of hypoxia-activated prodrugs is a promising strategy to address the limitations of photodynamic therapy (PDT) caused by a hypoxic tumor microenvironment. However, the controlled release of these hypoxia-activated prodrugs during PDT remains a challenge. In this study, we present a metal–organic framework (MOF) with a core–shell structure that can achieve a high PDT efficacy and on-demand release of hypoxia-activated prodrugs (AQ4N) for hypoxic tumor therapy. The nanocomposites were created by assembling zeolitic imidazolate frameworks (ZIF-8) onto the surface of AQ4N-encapsulated porphyrinic MOF, followed by surface functionalization with folic acid-conjugated polyethylene glycol. AQ4N is entrapped in the mesopores of MOFs, and it shows acidic environment-triggered release due to the degradation of the ZIF-8. When exposed to laser, porphyrinic MOFs can produce reactive oxygen species for PDT. At the same time, PDT exacerbates hypoxia at the tumor site, leading to the bioreduction of AQ4N to AQ4 for enhanced anticancer activity. This work presents a practical approach to improve the tumor-targeting and therapeutic efficiency of hypoxic tumors.
研究领域:
生物材料学
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癌症治疗
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2017
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IF 8.402
Shihong Shen,Youshen Wu,Ke Li,Ya Wang,Jimin Wu,Yun Zeng,Daocheng Wu
A novel strategy for the preparation of infinite coordination polymer nanoparticles (ICPs) based nanomedicines was developed, with which hyaluronic acid modified AQ4N-Cu(II)-gossypol nanoparticles (HA@AQ4N-Cu(II)-gossypol NPs) were obtained. This is a highly efficient nanomedicine, in which gossypol serves as a chemotherapeutic agent and a self-carrier material; Cu(II) serves as the connecting point and anti-tumor enhancer; AQ4N not only serves as a chemotherapeutic agent and self-carrier material, but also as the self-monitor based on its inherent fluorescence. HA@AQ4N-Cu(II)-gossypol NPs possessed a spherical shape with a dynamic size of 88.7 ± 7.4 nm, and the total drug-loading content and drug encapsulation efficiency are 77.41% and 100%, respectively. This nanomedicine has a multiple tumor-targeting ability caused by HA-receptor mediation and pH-responsive drug release. A significantly low combination index (0.097) of AQ4N and gossypol is ascertained. In vivo experiments indicate that it accumulates and significantly releases drugs at the tumor region. With the use of only one-fiftieth of AQ4N and half of gossypol of the generally administered dose, they can achieve significantly high anti-tumor efficiency with negligible side effects. Importantly, the switching-type changed fluorescence of AQ4N can be used for in vivo real-time self-monitoring of the drug release and distribution, which allows us to adjust the administration dose and time for different tumor types and stages for individual therapy.
研究领域:
纳米医学
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肿瘤学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Jingnan Li,Chengyan Luo,Tingyu Sun,Yinglin Zhou,Xinchang Huang,Dezhou Wu,Xirui Luo,Chao Zeng,Huanan Li
As a noninvasive treatment modality, high-intensity focused ultrasound (HIFU)-induced antitumor immune responses play a vital role in surgery prognosis. However, limited response intensity largely hinders postoperative immunotherapy. Herein, a hypoxia-specific metal–organic framework (MOF) nanosystem, coordinated by Fe3+, hypoxic-activated prodrug AQ4N, and IDO-1 signaling pathway inhibitor NLG919, is developed for the potentiating immunotherapy of HIFU surgery. The loaded AQ4N enhances the photoacoustic imaging effects to achieve accurate intraoperative navigation. Within the HIFU-established severe hypoxic environment, AQ4N is activated sequentially, following which it cooperates with Fe3+ to effectively provoke immunogenic cell death. In addition, potent NLG919 suppresses IDO-1 activity and degrades the immunosuppressive tumor microenvironment aggravated by postoperative hypoxia. In vivo studies demonstrate that the MOF-mediated immunotherapy greatly inhibits the growth of primary/distant tumors and eliminates lung metastasis. This work establishes a robust delivery platform to improve immunotherapy and the overall prognosis of HIFU surgery with high specificity and potency.
研究领域:
肿瘤学
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生物医学工程
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诊疗学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
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2021
·Vol. 21
·期 12
·2100229
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IF 4.979
Fangqin Song,Siqi Li,Chuanhao Sun,Ying Ji,Yan Zhang
The integration of hypoxia-activated chemotherapy with photodynamic therapy (PDT) has newly become a potent strategy for tumor treatment. Herein, a reactive oxygen species (ROS)-responsive drug carriers (PS@AQ4N/mPEG- b -PSe NPs) are fabricated based on the amphiphilic selenium-containing methoxy poly(ethylene glycol)-polycarbonate (mPEG- b -PSe), the hydrophobic photosensitizer (PS), and hypoxia-activated prodrug Banoxantrone (AQ4N). The obtained nanoparticles are spherical with an average diameter of 100 nm as characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS) respectively. The encapsulation efficiency of the PS and AQ4N reaches 92.83% and 51.04% at different conditions, respectively, by UV–vis spectrophotometer. It is found that the drug release is accelerated due to the good ROS responsiveness of mPEG- b -PSe and the cumulative release of AQ4N is up to 89% within 30 h. The cell test demonstrates that the nanoparticles dissociate when triggered by the ROS stimuli in the cancer cells, thus the PS is exposed to more oxygen and the ROS generation efficiency is enhanced accordingly. The consumption of oxygen during PDT leads to the increased tumor hypoxia, and subsequently activates AQ4N into cytotoxic counterpart to inhibit tumor growth. Therefore, the synergistic therapeutic efficacy demonstrates this drug delivery has great potential for antitumor therapy.
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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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yinglin Zhou,Xinchang Huang,Dezhou Wu,Xiaomei Xie,Hechun Li,Qi Wang,Yan Liao,Huanan Li
High-intensity focused ultrasound (HIFU) represents a game-changing breast-conserving treatment, with its induced immune response playing a crucial role in prognosis. However, the low immunogenicity and immunosuppressive microenvironment of tumors after surgery have prevented HIFU from generating strong antitumor immune responses, resulting in tumor recurrence and metastasis. Herein, we developed CaCO 3 -loaded metal–organic frameworks (MOFs) comprising Mn 2+ , hypoxia-activated prodrug banoxantrone (AQ4N), and stimulator of interferon genes (STING) agonist SR-717 to enhance HIFU-induced antitumor immunotherapy. Upon effective accumulation and drug release within tumor microenvironment (TME), MOFs exploit HIFU-exacerbated hypoxia to activate AQ4N, thereby inducing immunogenic cell death and enhancing tumor immunogenicity. Meanwhile, Mn 2+ enhances the activity of SR-717, synergistically amplifying STING activation and effectively promoting immune cell infiltration. Moreover, CaCO 3 complements immunotherapy by depleting lactate in TME, remodeling the immune microenvironment. As a result, MOFs enhance HIFU postoperative antitumor immune responses, significantly inhibiting tumor recurrence and metastasis. This work provides valuable insights to improve the prognosis of all surgical procedures, including HIFU.
研究领域:
肿瘤学
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免疫学
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
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IF 5.999
Zhaoyu Han,Yue Qian,Xiyue Gao,Dutao Yang,Yanfei Cai,Yun Chen,Jian Jin,Zhaoqi Yang
In recent years, laser-mediated photodynamic therapy and photothermal therapy have attracted widespread attention due to their minimally invasive, easy to operate characteristics and high specificity. However, the traditional photodynamic or photothermal therapy exist several shortcomings such as the hypoxic microenvironment, intracellular heat shock proteins or complex operation. In this study, covalent organic framework (COF) was used as the drug carrier to equip with the photosensitizer indocyanine green (ICG) and the hypoxia-activating prodrug AQ4N. The hyaluronic acid (HA) was modified on the surface of COF to obtain the [email protected] /AQ4N drug delivery system. HA-modified COF delivery systems can target tumor cells through recognize CD44 which is overexpressed in the surface of tumor cells membrane . Under the irradiation of single NIR laser , ICG that can excite the nanoplatform simultaneously produces a combined effect of photodynamic and photothermal. At the same time, photodynamic therapy through depleting intracellular oxygen exacerbates the hypoxic state of the tumor microenvironment, which in turn enhances AQ4N reduced to chemotherapeutic drug AQ4, producing a synergistic cascade antitumor effect . The results of our study by tumor cell and tumor spheroids indicated that the hypoxia-activated multi-functional nanoplatform could effectively inhibit the growth and metastasis of triple-negative breast cancer.
研究领域:
癌症治疗
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材料科学
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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
Advanced Healthcare Materials
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2022
·Vol. 11
·期 19
·2200776
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IF 11.092
Xingbo Wang,Yan Cheng,Xiaoqing Han,Jiao Yan,Yunyun Wu,Panpan Song,Yanjing Wang,Xi Li,Haiyuan Zhang
Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.
研究领域:
癌症治疗
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材料科学
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免疫学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-23
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IF 10.2
Pan Yi,Liu Longcai,He Yichen,Ye Luyi,Zhao Xin,Hu Zhiming,Mou Xiaozhou,Cai Yu
Background Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients. Results In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models. Conclusion Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.
研究领域:
肿瘤学
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生物医学工程
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药学
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诊断成像
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）