Theranostics
·
2020
·
IF 8.579
Chao Fang,Dong Cen,Yifan Wang,Yongjun Wu,Xiujun Cai,Xiang Li,Gaorong Han
Abnormal tumor microenvironment, such as hypoxia, interstitial hypertension and low pH, leads to unexpected resistance for current tumor treatment. The development of versatile drug delivery systems which present responsive characteristics to tumor microenvironment (TME) has been extensively carried out, but remains challenging. In this study, zeolitic imidazolate framework-8 (ZIF-8) coated ZnS nanoparticles have been designed and prepared for co-delivery of ICG/TPZ molecules, denoted as ZSZIT, for H 2 S-amplified synergistic therapy. Methods: The ZSZ nanoparticles were characterized using SEM, TEM and XRD. The in vitro viabilities of cancer cells cultured with ZSZIT under normoxia/hypoxia conditions were evaluated by cell counting kit-8 (CCK-8) assay. In addition, in vivo anti-tumor effect was also performed using male Balb/c nude mice as animal model. Results: ZSZIT shows cascade PDT and hypoxia-activated chemotherapeutic effect under an 808nm NIR irradiation. Meanwhile, ZSZIT degrades under tumor acidic environment, and H 2 S produced by ZnS cores could inhibit the expression of catalase, which subsequently favors the hypoxia and antitumor effect of TPZ drug. Both in vitro and in vivo studies demonstrate the H 2 S-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy. Conclusion: This cascade H 2 S-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.
研究领域:
纳米医学
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肿瘤学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Lianxiao Zhang,Qijie Diao,Bo Li,Xuedan Yang,Teng Wang,Rui Chen,Tianze Jiang,Xia Zhao
Breast cancer is a common malignant tumor in women worldwide, and its high metastasis is the main reason for high mortality. Especially under hypoxic microenvironments, the upregulation of hypoxia-inducible factor 1-alpha (HIF-1α) can activate the transcription factor Twist and promote tumor metastasis through epithelial-mesenchymal transformation (EMT). Here, MnO 2 nanosheets are synthesized with oxidase-like activity using fucoidan as a protective agent, and construct a multifunctional delivery system MnO 2 @DNAzyme-TPZ (MDT) by loading DNAzymes and hypoxia-activated prodrug Tirapazamine (TPZ) for tumor treatment and metastasis inhibition. MDT kills tumors by converting O 2 into reactive oxygen species (ROS) through MnO 2 nanozymes, and inhibits tumor metastasis by selectively silencing the tumor metastasis-related Twist gene through DNAzymes. TPZ enhances tumor killing under hypoxic environments and synergistically inhibits tumor metastasis by reducing the expression of HIF-1α. MDT significantly inhibits tumor growth and metastasis in vivo in an in situ tumor model. The strategy of combining selective gene silencing based on DNAzymes with nanozymes and hypoxia-activated prodrug provides a new approach to anti-tumor metastasis therapy.
研究领域:
肿瘤学
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生物医学工程
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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
Gels
·
2026
·Vol. 12
·期 9
·781
·
IF 6.4
Ling Li,Kexin Wang,Zhe Song,Hongan Tian,Cai Wang,Ling Zhang,Houqiang Yu
TPZ is a hypoxia-activated anticancer agent that exerts selective cytotoxicity within hypoxic tumor microenvironments. Although intratumoral injection of TPZ can achieve localized antitumor activity, the drug is prone to rapid diffusion and clearance from the injection site, limiting its long-term retention and thereby reducing therapeutic durability and overall efficacy. To achieve sustained release and prolonged retention of TPZ in subcutaneous tumors, a thermosensitive nanogel loaded with TPZ (TPZ@PNA-TNG) was developed. By thoroughly mixing 3 mg/mL TPZ with 6 wt% PNA-TNG, the resulting formulation enabled continuous slow release of TPZ following intratumoral injection, resulting in favorable therapeutic outcomes. The sol–gel phase transition behavior of TPZ@PNA-TNG was investigated using the inverted vial method and rheological measurements. In vivo antitumor studies demonstrated that a single administration of TPZ@PNA-TNG effectively suppressed tumor progression, with tumor volume decreasing to 0.72 ± 0.04 times its initial size over a 14-day period. Mechanistically, TPZ@PNA-TNG markedly enhanced antitumor immune responses, inhibited tumor cell proliferation, promoted apoptosis and anti-angiogenesis, and ultimately induced extensive ischemic necrosis within subcutaneous tumors. In addition, owing to the prolonged intratumoral retention capability of PNA-TNG, TPZ@PNA-TNG enabled sustained local delivery of TPZ, thereby significantly reducing systemic toxicity and adverse effects associated with TPZ while maintaining favorable biocompatibility. These findings highlight the therapeutic potential of TPZ@PNA-TNG for cancer therapy applications.
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DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Senyi Gong,Mengdi Shang,Runnan Shao,Sen Li,Li He,Yanfei Cai,Teng Wang,Jian Jin,Zhaoqi Yang
Chemotherapy as a primary treatment for breast cancer is limited due to drug resistance in clinical treatment. The rapid proliferation and invasive biological properties of breast cancer, resulting in intratumoral hypoxia and adaptive antioxidation, are common manifestations of drug-resistant breast cancer. Photodynamic therapy is a potential strategy to overcome drug resistance, but its effectiveness is often limited by tumor hypoxia. In order to overcome the problem of tumor hypoxia and improve the effectiveness of photodynamic therapy, a strategy that employs ZIF-90 nanoparticles simultaneously delivering a hypoxia-induced drug (TPZ) and photosensitizer Ce6 labeled antisense nucleic acid (Ce6-G3139) into breast cancer cells was developed. Owing to the pH responsiveness of ZIF-90, TPZ and Ce6-G3139 are able to be efficiently released inside the tumor microenvironment. First, Ce6-G3139 can perform gene therapy, downregulating the expression of antiapoptotic protein BCL-2 and accelerating cell apoptosis. On the other hand, photosensitizer Ce6 can undergo photodynamic therapy (PDT), producing reactive oxygen species that interfere with the apoptosis mechanism of cells. More importantly, although the continuous consumption of oxygen in PDT aggravates the hypoxic environment of the tumor, the hypoxic-induced chemotherapy drug was further activated. Our research results indicate that the designed strategy targeting the hypoxic microenvironment of drug-resistant breast cancer exhibits significant anticancer effects both in vitro and in vivo, favoring the development of a PDT treatment paradigm that is effective against drug resistance under hypoxic conditions.
研究领域:
肿瘤学
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纳米技术
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药学
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生物医学工程
✓ 已验证
DOI
高影响因子
Nanoscale
·
2022
·Vol. 15
·期 1
·237-247
·
IF 8.307
Panli Han,Lianxue Zhang,Yaqi Fu,Youyu Fu,Jianxiang Huang,Jinlin He,Peihong Ni,Taimoor Khan,Yang Jiao,Zaixing Yang,Ruhong Zhou
The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (e.g., 2 Gy) of X-ray and reactive oxygen species on the basis of diselenide block copolymers. Upon the external X-ray stimulus, the system accurately released encapsulated PTX at tumor sites and remarkably improved tumor hypoxia levels by causing severe damage to tumor blood vessels. Subsequently, these enhanced tumor hypoxia levels effectively activated the reduction of TPZ into benzotriazinyl free radicals, which significantly improved the antitumor efficacy of our system against 4T1 breast cancer cells with an initial tumor volume of 500 mm3. Moreover, the dual-stimulus coordinated and controlled release of PTX was found to largely avoid the off-target effects of PTX on normal cells while exhibiting very limited side effects in experimental mice. The current novel strategy for regulating tumor hypoxia levels offers an effective and safe way to activate TPZ for the treatment of large solid tumors.
研究领域:
药学
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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
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Gaoqian Zhao,Yan Jin,Shutao Gao,Tingshan Xiao,Miao Fan,Dandan Liu,Jinchao Zhang,Zhenhua Li,Xiaohan Zhou,Huifang Liu
The low sensitivity of hypoxic regions in solid tumors to radiotherapy and chemotherapy remains a major obstacle to cancer treatment. By taking advantage of hypoxic-activated prodrugs, tirapazamine (TPZ), generating cytotoxic reductive products and the glucose oxidase (GOx)-based glucose oxidation reaction, we designed a nanodrug-loading system that combined TPZ-induced chemotherapy with GOx-mediated cancer-orchestrated starvation therapy and cancer oxidation therapy. In this work, we first prepared mesoporous silica (MSN) loaded with TPZ. Then, in order to prevent the leakage of TPZ in advance, the surface was coated with a layer of carMOF formed by Fe3+ and carbenicillin (car), and GOx was adsorbed on the outermost layer to form the final nanosystem MSN-TPZ@carMOF-GOx (MT@c-G). GOx could effectively consume oxygen and catalyzed glucose into gluconic acid and hydrogen peroxide. First, the generated gluconic acid lowered the pH of tumor tissues, promoted the decomposition of carMOF, and released TPZ. Second, oxygen consumption could improve the degree of hypoxia in tumor tissues, so that enhanced the activity of TPZ. Furthermore, GOx could generate cancer-orchestrated starvation/oxidation therapy. Therefore, our study provided a new strategy that TPZ combined with GOx achieved starvation/oxidation/chemotherapy for enhancing anticancer effects in hypoxic regions.
研究领域:
癌症研究
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药物科学
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纳米医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Shipeng Ning,Xingliang Dai,Weiwei Tang,Qinglong Guo,Meng Lyu,Daoming Zhu,Wei Zhang,Haisheng Qian,Xiaxi Yao,Xianwen Wang
Sonodynamic therapy (SDT) is a promising strategy for tumor treatment that satisfies all requirements of penetrating deep-seated tissues without causing additional trauma. However, the hypoxic tumor microenvironment impairs the therapeutic effect of SDT. The synergistic treatment of oxygen concentration-dependent SDT and bio-reductive therapy has been proven to be an effective approach to improve the therapeutic efficiency of SDT by exploiting tumor hypoxia . Herein, a biomimetic drug delivery system (C-TiO 2 / [email protected] ) was successfully synthesized for combined SDT and hypoxia-activated chemotherapy, which was composed of tirapazamine (TPZ)-loaded C-TiO 2 hollow nanoshells (HNSs) as the inner cores and cancer cell membrane (CM) as the outer shells. C-TiO 2 HNSs coated with CM achieved tumor targeting via homologous binding. C-TiO 2 @CM as a nanocarrier loaded with TPZ in the presence of the trapping ability of CM and the special cavity structure of C-TiO 2 HNSs. Moreover, C-TiO 2 HNSs as sonosensitizers killed cancer cells under ultrasound (US) irradiation. Oxygen depletion during SDT induced a hypoxic environment in the tumor to activate the killing effect of co-delivered TPZ, thereby obtaining satisfactory synergistic therapeutic effects. In addition, C-TiO 2 @CM exhibited remarkable biocompatibility without manifest damage and toxicity to the blood and major organs of the mice. The study highlighted that C-TiO 2 / [email protected] served as a powerful biomimetic drug delivery system for effective SDT by exploiting tumor hypoxia. Statement of significance • C-TiO 2 @CM achieved tumor targeting via homologous binding. • C-TiO 2 hollow nanoshells could be used as a sonosensitizer and drug carrier for synergistic SDT and hypoxia-activated chemotherapy. • C-TiO 2 / [email protected] showed no obvious toxicity under the injection dose.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 13
·4247
·
IF 4.927
Xuan Wang,Qing Chen,Congxiao Lu
Hypoxia-activated prodrugs (HAPs) with selective toxicity in tumor hypoxic microenvironments are a new strategy for tumor treatment with fewer side effects. Nonetheless, the deficiency of tumor tissue enrichment and tumor hypoxia greatly affect the therapeutic effect of HAPs. Herein, we design an active targeted drug delivery system driven by AS1411 aptamer to improve the tumor tissue enrichment of HAPs. The drug delivery system, called[email protected](TA-MOF), uses iron-based MOF as a carrier, surface-modified nucleolin aptamer AS1411, and the internal loaded hypoxia activation prodrug TPZ. Compared with naked MOF, the AS1411-modified MOF showed a better tumor targeting effect both in vitro and in vivo. MOF is driven by GSH to degrade within the tumor, producing Fe2+, and releasing the cargo. This process leads to a high consumption of the tumor protective agent GSH. Then, the Fenton reaction mediated by Fe2+not only consumes the intracellular oxygen but also increases the intracellular production of highly toxic superoxide anions. This enhances the toxicity and therapeutic effect of TPZ. This study provides a new therapeutic strategy for cancer treatment.Keywords:aptamer;MOFs;chemodynamic;chemotherapy;breast cancer
研究领域:
癌症治疗
·
药物递送系统
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材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Youqiang Fang,Xing Luo,Yanteng Xu,Zheng Liu,Rachel L. Mintz,Haiyang Yu,Xuan Yu,Kai Li,Enguo Ju,Haixia Wang,Zhaohui Tang,Yu Tao,Mingqiang Li
As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic- co -glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1 α , vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
外科手术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2023
·
IF 4.7
Jingsong Lu,Jing Yu,Wensheng Xie,Xiaohan Gao,Zhenhu Guo,Zeping Jin,Ying Li,Abdul Fahad,Neema Ufurahi Pambe,Shenglei Che,Yen Wei,Lingyun Zhao
Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY COMMUNICATIONS
·
2023
·
IF 3.8
Feng Ouyang,Li Zhao,Qi Shuai
Viscous tumour tissue seriously affects the effective delivery of nanodrugs and reduces their anti-tumour effect. In order to solve this problem, a nanomotor (Cy7@ZIF-8@TPZ) for penetrating tumour tissue was synthesized. A new amphiphilic molecule Cy7 was designed and synthesized to wrap ZIF-8 loaded with TPZ to obtain the final nanomotor. The synthesized Cy7 can not only realize photodynamic therapy (PDT) and photothermal therapy (PTT) simultaneously under single-wavelength illumination, but also promote the movement of nanoparticles through thermal drive. Through the targeting ability of Cy7 and the enhanced permeability and retention (EPR) effect, the nanomotor can conduct directional deep puncture under illumination. The oxygen continuously consumed by PDT further activates hypoxia-activated chemotherapy, and the combined PTT/PDT/hypoxia-activated CT therapy greatly enhances the anti-tumour efficacy of Cy7@ZIF-8@TPZ. In addition, light-degradable Cy7, acid-degraded ZIF-8 and hypoxia-activated TPZ greatly reduce the side effects of nanomotors.
研究领域:
癌症治疗
·
纳米技术
·
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）