COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Ruoning Wang,Qifan Liang,Xinru Zhang,Zhenning Di,Xiaohong Wang,Liuqing Di
Temozolomide (TMZ), as the first-line chemotherapeutic agent, relies on inducing DNA methylation of O 6 -guanine for treating glioma. However, the survival time of patients are hardly exceeded 14.5 months, attributing to inevitable drug resistance and systematic toxicity after long-term administration. Herein, reassembly-exosomes (R-EXO) deriving from homologous glioma cells is proposed to carry TMZ and Dihydrotanshinone (DHT) for reversing drug resistance and enhancing lesions-targeted drug delivery, defined as R-EXO-TMZ/DHT (R-EXO-T/D). It is found that R-EXO-T/D share various advantages, including preferable blood-brain barrier (BBB)-penetrating ability with nanomemter size, tumor-homing accumulation with homologous effects, as well as potentiated antitumor activity with overcoming TMZ resistance and triggering immune response. This work develops a new strategy for site-specific drug delivery, showing a promising application of drug compatibility in glioma treatment.
研究领域:
药理学
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肿瘤学
·
纳米医学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2019
·Vol. 17
·期 1
·1-12
·
IF 5.345
Zeng Xiaofan,Wang Qi,Tan Xuan,Jia Le,Li Yuwei,Hu Mingdi,Zhang Zhijie,Bai Xicheng,Zhu Yanhong,Yang Xiangliang
Background Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence.Methods Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO.Results NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only.Conclusion These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.
研究领域:
肿瘤学
·
纳米技术
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治疗策略
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2024
·
IF 3.6
Chongwen Ren,Qingqing Tu,Jinchao He
Glioma cancer is the primary cause of cancer-related fatalities globally for both men and women. Traditional chemotherapy treatments for this condition frequently result in reduced efficacy and significant adverse effects. This investigation developed a new drug delivery system for the chemotherapeutic drug temozolomide (TMZ) using pH-sensitive drug delivery zeolitic imidazolate frameworks (ZIF-8). These nanoplatforms demonstrate excellent biocompatibility and hold potential for cancer therapy. Utilizing the favorable reaction milieu offered by ZIFs, a ‘one-pot method’ was employed for the fabrication and loading of drugs, leading to a good capacity for loading. TMZ@TA@ZIF-8 NPs exhibit a notable response to an acidic milieu, resulting in an enhanced drug release pattern characterized by a controlled release outcome. The effectiveness of TMZ@TA@ZIF-8 NPs in inhibiting the migration and invasion of U251 glioma cancer cells, as well as promoting apoptosis, was confirmed through various tests, including MTT (3-(4,5)-dimethylthiahiazo(-z-y1)) assay, DAPI/PI dual staining, and cell scratch assay. The biochemical fluorescent staining assays showed that TMZ@TA@ZIF-8 NPs potentially improved ROS, reduced MMP, and triggered apoptosis in U251 cells. In U251 cells treated with NPs, the p53, Bax, Cyt-C, caspase-3, −8, and −9 expressions were significantly enhanced, while Bcl-2 expression was diminished. These outcomes show the potential of TMZ@TA@ZIF-8 NPs as a therapeutic agent with anti-glioma properties. Overall, the pH-responsive drug delivery systems we fabricated using TMZ@TA@ZIF-8 NPs show great potential for cancer treatment. This approach has the potential to make significant contributions to the improvement of cancer therapy by overcoming the problems associated with TMZ-based treatments.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 27
·期 1
·79
·
IF 4.9
Xiaoyu Liu,Yunfei Liu,Wenxuan Li,Qianwen Wang,Ziyu Huang,Xiyu Cheng,Qiong Yan,Honggang Hu
Glioblastoma (GBM) represents a highly invasive primary malignant tumor within the central nervous system (CNS). Temozolomide (TMZ), a first-line chemotherapy agent for GBM treatment, has significant limitations, including drug resistance, poor water solubility, a short half-life, and notable toxic side effects. The innovation of the TMZ dosage form is pivotal for enhancing its therapeutic efficacy. In this study, solid lipid nanoparticles (SLN) loaded with Angiopep-2 (A2) and TMZ (TMZ-A2SLN), a nanopolymer featuring a solid spherical morphology and a particle size of approximately 100 nm, were constructed. The combined effect of TMZ-A2SLN and small-interfering RNA (siRNA) that can knock down the expression of theHOXB9gene (siHOXB9) augmented the sensitivity of the glioma cell line U251 to TMZ. Under the combined effect, the viability of U251 cells was reduced by 77%. Meanwhile, the mortality rate increased by approximately 45%, and the cell apoptosis rate rose by around 36%. The number of cells arrested in the G2/M and S phases rose. Proteomic analysis indicates that TMZ-A2SLN might be implicated in the pro-inflammatory signaling cascade, tumor migration, invasion, and angiogenesis during the treatment of glioma cells. Moreover,HOXB9may play a crucial regulatory role in the PPAR signaling pathway, the neural signaling pathway, the phospholipase D signaling pathway, the IL-17 signaling pathway, mineral absorption, and other pathways during glioma cell treatment.
研究领域:
肿瘤学
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神经肿瘤学
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纳米医学
·
分子生物学
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药理学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiu Wang,Baoqin Song,Mengru Wu,Lijing Qin,Wanjun Liang
Gliomas are a group of highly malignant tumors that are prone to recurrence after surgery. Due to the limitation of the blood-brain barrier (BBB), most antitumor drugs cannot cross it. Therefore, improving the delivery efficiency of antitumor drugs in their treatment remains a significant challenge. Herein, we report a unique cellular biomimetic drug delivery system (CTP@RAW) that benefits from the exceptional immune homing and long-term tracking ability of RAW 264.7 cells to specifically penetrate BBB and target tumor sites. The drug (TMZ) is encapsulated in RAW264.7 to avoid being cleared or degraded by the blood, improve bioavailability and reduce systemic toxicity. And that, owning to polydopamine (PDA) coating on the quantum dots-drug nanoparticles, which can endogenously and controllably release TMZ in response to certain tumor microenvironment (high GSH and low pH). This delivery system can also achieve precise localization and real-time visualization of tumors via fluorescence imaging. The released drugs effectively inhibit tumor growth by regulating cytokine expression levels, including GFAP, Ki67, Caspase-3, and TNF-α. Our study demonstrates that this drug delivery system can cross BBB, improve drug delivery efficiency, and has excellent potential for visualization and precision treatment of in situ gliomas.
研究领域:
肿瘤学
·
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
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
·
药剂学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Pinxin Lv,Zhanfeng Wang,Xinghui Si,Jing Su,Zhifei Yu,Hongquan Yu,Guofeng Ji,Wantong Song
Glioblastoma (GBM), a prevalent and aggressive brain tumor, poses significant treatment challenges due to its rapid progression and the difficulty in achieving complete surgical resection. The current treatment regime, primarily surgery followed by radiotherapy and chemotherapy, offers limited success, with a five-year survival rate of less than 10%. For addressing the challenges faced in the treatment of GBM, an approach using a biopolymer implant constructed with dynamic reversible covalent bonds, was designed to achieve controlled and constant-rate release of chemotherapy drug (Temozolomide, TMZ), immune adjuvant (Resiquimod, R848) and checkpoint inhibitor (5-carboxy-8-hydroxyquinoline, IOX1). The safety evaluation demonstrated the biocompatibility of the implants, with no significant inflammatory response or adverse effects on various systemic organs. In vivo antitumor study showed that the local delivery of drug combination via this implant significantly inhibited tumor recurrence of orthotopic GBM. Immune analysis revealed that the combination of the three drugs effectively activated systemic antitumor immune responses and induced memory effects. The synergistic mechanism of the drug combination was further validated by RNA whole sequencing. The innovative approach of combining chemotherapy and immunotherapy in biopolymer immune implants for GBM treatment showed promising and opens new avenues for treating GBM, particularly in addressing postoperative recurrence. Statement of Significance Our research introduces a pioneering approach in treating orthotopic brain glioblastoma (GBM), characterized by inevitable tumor recurrence, poor immune infiltration and the restrictive nature of the blood-brain barrier. To break the impasse of ineffective treatment for GBM, the innovative use of dynamically reversible covalent bonds in polymer matrix ensures the controlled, stable and sustained release of drug combinations of the chemotherapeutic agent temozolomide, immune adjuvants and checkpoint inhibitors, which maintains the optimal concentration in the tumor, overcoming problems associated with conventional chemotherapy such as systemic toxicity and low tumor targeting. Empirical evidence from in vivo experiments on the rat GBM model demonstrates significant outcomes: 90% tumor size reduction and prolonged survival with over 70% tumor cure rate.
研究领域:
肿瘤学
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生物材料科学
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免疫治疗
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Computational Intelligence and Neuroscience
·
2022
·
IF 3.12
Zhihua Chen,Guofeng Zhu,Chunpeng Sheng,Jianwei Lei,Sihui Song,Jianming Zhu
Temozolomide (TMZ), an oral alkylating agent, is the widely used first-line chemotherapeutic reagent for glioma in clinical practice. However, TMZ-induced autophagy is another cellular process favoring glioma cell survival. This study aimed to explore whether hispidulin can facilitate TMZ-induced cell death of glioma. The MTT assay showed that coadministration with hispidulin and TMZ could significantly decrease the viability of glioma U87MG cells. Meanwhile, hispidulin administration was also observed to promote TMZ-induced apoptosis. Furthermore, additional hispidulin treatment further elevated TMZ-induced expression of Bax, cleaved-caspase-9, and cleaved-caspase-3 protein but decreased Bcl-2 protein expression in U87MG cells. We also observed that hispidulin suppressed TMZ-induced autophagy to promote apoptosis, as showed by decreased AVOs and LC3B-I/II protein expression. These results collectively suggested that the combination of hispidulin and TMZ could improve the antitumor efficiency of TMZ against malignant gliomas.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2016
·Vol. 11
·期 8
·e0161435
·
IF 3.057
Daoxiang Huang,Chao Lin,Xuejun Wen,Shuying Gu,Peng Zhao
This study aims to develop a novel device with nanofiber membrane capable of sustained release of temozolomide (TMZ) and neuron growth factor (NGF). An improved bio-availability of TMZ and NGF in surroundings proximal to the device was expected to be attained for a prolonged period of time. The device was developed by integrating TMZ-doped polycaprolactone (PCL) nanofiber (TP) membrane and NGF-coated PCL (NGFP) membrane using sodium alginate hydrogel. TP was prepared by direct electrospinning of TMZ/PCL. NGFP membrane was developed by layer-by-layer assembling technology. The incorporation of TMZ-doped nanofiber and NGFP nanofiber in the device was confirmed by scanning electron microscopy. The number of NGF layer in NGF-coated PCL membrane could be readily measured with energy spectrum analysis. The in vitro release study showed that TP-NGFP-TP membrane could efficiently liberate TMZ to inhibit the growth of C6 glioma cells, and sufficient NGF to induce the differentiation of PC12 neuron cells over four weeks. Such TP-NGFP-TP membrane device can be employed as a tampon to fill up surgical residual cavity and afford residual glioma removal, structural support, hemostasis, and local neural tissue reconstruction in the surgical treatment of glioma. The study opens a horizon to develop multifunctional biomaterial device for maximized glioma treatment efficacy.
研究领域:
生物医学工程
·
神经科学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Shuai Wu,Ya Wang,Yunfan Li,Minyao Qiu,Yuan Zhong,Maolan Zhang,Haifeng Yang,Jianshu Li,Wei Wu
Clinical treatment of temozolomide (TMZ)-resistant glioblastoma (GBM) remains a significant challenge. This study aims to develop a multifunctional biomimetic Nano-AUTAC (BM@pPPD/TMZ) that can selectively degrade β-catenin via autophagy, thereby overcoming TMZ resistance in GBM. BM@pPPD/TMZ is capable of penetrating the blood-brain barrier (BBB), targeting GBM lesions via microglia-derived membrane camouflage, and inducing degradation of β-catenin through the autophagy-lysosomal pathway. For improving the selective and efficient degradation of β-catenin, BM@pPPD/TMZ is functionalized with a tri-functional peptide comprising a β-catenin-binding domain, a cathepsin B (CTSB)-cleavable GLFG linker, and a phosphatidylserine (PS)-targeting motif. In the GBM microenvironment, the elevated CTSB triggers linker cleavage, promoting membrane shedding and enhancing the cellular uptake. Meanwhile, the incorporation of the cationic lipid DOTAP promotes autophagosome formation, further facilitating degradation of β-catenin. Both in vitro and in vivo studies demonstrate that BM@pPPD/TMZ is able to effectively penetrate the BBB and accumulate within tumor lesion, concurrently promoting β-catenin degradation and MGMT downregulation. This finding provides a promising nanotherapeutic strategy for overcoming TMZ resistance and improving GBM therapeutic efficacy.
研究领域:
纳米医学
·
癌症治疗
·
分子生物学
·
神经肿瘤学
·
自噬研究
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
Nano Research
·
2023
·
IF 9.9
Zhang Yufei,Cheng Qian,Xue Yuhao,Yao Kai,Syeda Madiha Zahra,Xu Jian,Wu Jianheng,Wang Zhenjie,Tang Longguang,Mu Qingchun
Glioma is the most common primary craniocerebral tumor caused by the cancerous growth of glial cells in the brain and spinal cord. Currently, standard treatment is the surgical resection followed by concurrent radiation and chemotherapy. However, the blood-brain barrier (BBB) prevents most antitumor drugs from entering the brain and reduces their efficacy, especially in low-grade glioma. Since L-type amino acid transporter 1 (LAT1) is highly expressed in glioma cells and mediates drug transport across the BBB, it is a promising target for drug delivery and treatment of glioma. Temozolomide (TMZ) is the first-line treatment for glioma, however, patients often exhibit drug resistance at advanced stage. A multikinase inhibitor and inducer of ferroptosis, sorafenib can improve the therapeutic effects of TMZ. Therefore, to optimize the glioma treatment and cross the BBB, we designed LAT1-targeting nanoparticles co-loaded with TMZ and sorafenib. Our results from both in vitro and in vivo studies confirmed that LAT1-targeting nanoparticles significantly increased the cellular uptake, cytotoxicity, accumulation at tumor site, and the anti-tumor efficacy compared to the non-target nanoparticles. Therefore, LAT1 can be used as a potential target for brain-targeted drug delivery, and sorafenib-induced ferroptosis can aid the anti-glioma efficacy of TMZ.
研究领域:
肿瘤学
·
神经科学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MICROENCAPSULATION
·
2024
·
IF 3
Lili Li,Lin Jing,Zijun Tang,Jingguo Du,Yonglong Zhong,Xu Liu,Mingqing Yuan
Aim To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects.Methods Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip.Results BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of −22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity.Conclusion BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
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）