TECHNOLOGY IN CANCER RESEARCH & TREATMENT
·
2024
·
IF 2.7
Li-Hong Liu,Yu-Feng Liu,Hong-Bo Zhang,Xiao-Lei Liu,Han-Wen Zhang,Biao Huang,Fan Lin,Wei-Hua Li
PurposeDevelop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting.MethodsCombined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors.ResultsANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed.ConclusionThis targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.
研究领域:
纳米技术
·
神经肿瘤学
·
药物递送系统
·
医学成像
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2022
·
IF 6.1
Xiaodong Sun,Tengjiao Fan,Guohui Sun,Yue Zhou,Yaxin Huang,Na Zhang,Lijiao Zhao,Rugang Zhong,Yongzhen Peng
Chloroethylnitrosoureas (CENUs) exert antitumor activity via producing dG-dC interstrand crosslinks (ICLs). However, tumor resistance make it necessary to find novel strategies to improve the therapeutic effect of CENUs. 2-Deoxy-D-glucose (2-DG) is a well-known glycolytic inhibitor, which can reprogram tumor energy metabolism closely related to tumor resistance. Here, we investigated the chemosensitization effect of 2-DG on l,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against glioblastoma cells and the underlying mechanisms. We found that 2-DG significantly increased the inhibitory effects of BCNU on tumor cells compared with BCNU alone, while 2-DG showed no obvious enhancing effect on the BCNU-induced cytotoxicity for normal HaCaT and HA1800 cells. Proliferation, migration and invasion determinations presented the same trend as survival on tumor cells. 2-DG plus BCNU increased the energy deficiency through a more effective inhibition of glycolytic pathway. Notably, the combination of 2-DG and BCNU aggravated oxidative stress in glioblastoma cells, along with a significant decrease in glutathione (GSH) levels, and an increase in intracellular reactive oxygen species (ROS). Subsequently, we demonstrated that the combination treatment led to increased apoptosis via activating mitochondria and endoplasmic reticulum stress (ERS) related apoptosis pathways. Finally, we found that the dG-dC level was significantly increased after 2-DG pretreatment compared to BCNU alone by HPLC-ESI-MS/MS analysis. Finally, in vivo , 2-DG plus BCNU significantly suppressed tumor growth with lower side effects compared with BCNU alone in tumor-bearing mice. In summary, we proposed that 2-DG may have potential to increase the sensitivity of glioblastoma cells to BCNU by regulating glycolysis, ROS and ERS pathways in clinical setting.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-21
·
IF 10.2
Li Duo,Ren Ting,Ge Yunxuan,Wang Xiaoli,Sun Guohui,Zhang Na,Zhao Lijiao,Zhong Rugang
Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O 6 position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O 6 -alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery. In the light of the features of tumor microenvironment, we constructed a multifunctional hypoxia/esterase-degradable nanomicelle with AGT inhibitory activity named HACB NPs for tumor-targeting BCNU delivery and tumor sensitization. HACB NPs was self-assembled from hyaluronic acid azobenzene AGT inhibitor conjugates, in which O 6 -BG analog acted as an AGT inhibitor, azobenzene acted as a hypoxia-responsive linker and carboxylate ester bond acted as both an esterase-sensitive switch and a connector with hyaluronic acid (HA). The obtained HACB NPs possessed good stability, favorable biosafety and hypoxia/esterase-responsive drug-releasing ability. BCNU-loaded HACB/BCNU NPs exhibited superior cytotoxicity and apoptosis-inducing ability toward the human uterine cervix carcinoma HeLa cells compared with traditional combined medication of BCNU plus O 6 -BG. In vivo studies further demonstrated that after a selective accumulation in the tumor site, the micelles could respond to hypoxic tumor tissue for rapid drug release to an effective therapeutic dosage. Thus, this multifunctional stimulus-responsive nanocarrier could be a new promising strategy to enhance the anticancer efficacy and reduce the side effects of BCNU and other CENUs.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Duo Li,Xiaoli Wang,Kaishuo Han,Yaqian Sun,Ting Ren,Guohui Sun,Na Zhang,Lijiao Zhao,Rugang Zhong
Carmustine (BCNU) is a typical chemotherapy used for treatment of cerebroma and other solid tumors, which exerts antitumor effect by inducing DNA damage at O 6 position of guanine. However, the clinical application of BCNU was extremely limited due to the drug resistance mainly mediated by O 6 -alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability. To overcome these limitations, we developed a hypoxia-responsive nanomicelle with AGT inhibitory activity, which was successfully loaded with BCNU. In this nano-system, hyaluronic acid (HA) acts as an active tumor-targeting ligand to bind the overexpressing CD44 receptors on the surface of tumor cells. An azo bond selectively breaks in hypoxic tumor microenvironment to release O 6 -benzylguanine (BG) as AGT inhibitor and BCNU as DNA alkylating agent. The obtained HA-AZO-BG NPs with shell core structure had an average particle size of 176.98 ± 11.19 nm and exhibited good stability. Meanwhile, HA-AZO-BG NPs possessed a hypoxia-responsive drug release profile. After immobilizing BCNU into HA-AZO-BG NPs, the obtained HA-AZO-BG/BCNU NPs exhibited obvious hypoxia-selectivity and superior cytotoxicity in T98G, A549, MCF-7 and SMMC-7721 cells with IC 50 at 189.0, 183.2, 90.1 and 100.1 μm, respectively, under hypoxic condition. Near-infrared imaging in HeLa tumor xenograft models showed that HA-AZO-BG/DiR NPs could effectively accumulate in tumor site at 4 h of post-injection, suggesting its good tumor-targetability. In addition, in vivo anti-tumor efficacy and toxicity evaluation indicated that HA-AZO-BG/BCNU NPs was more effective and less harmful compared to the other groups. After treatment, the tumor weight of HA-AZO-BG/BCNU NPs group was 58.46 % and 63.33 % of the control group and BCNU group, respectively. Overall, HA-AZO-BG/BCNU NPs was expected to be a promising candidate for targeted delivery of BCNU and elimination of chemoresistance.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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