Pharmaceutics
·
2025
·Vol. 18
·期 1
·10
·
IF 5.5
Jing Zhang,Wenhao Jiang,Lei Hu,Qing Du,Nina Filipczak,Satya Siva Kishan Yalamarty,Xiang Li
Objective:This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO2) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety.Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was employed to quantify manganese content. To assess siRNA stability within the system, samples were incubated with 50% fetal bovine serum (FBS) before agarose gel electrophoresis analysis. Additionally, cellular internalization by 4T1 cells and in vitro photothermal conversion efficiency of the formulation were evaluated. ICP-OES was further utilized to investigate the in vivo pharmacokinetics and tissue distribution of manganese. Animal model studies were conducted to assess the anti-breast cancer efficacy of PDA@Mn-siSur-c-NPs in combination with infrared irradiation.Results: The newly developed PDA@Mn-siSur-c-NPs demonstrated superior siRNA protection, reduced toxicity, and high photothermal conversion capacity. When combined with photothermal therapy (PTT), these nanoparticles exerted enhanced synergistic anti-tumor effects. Delivery of survivin siRNA resulted in a significant downregulation of survivin protein expression in tumor tissues. Moreover, magnetic resonance imaging (MRI) confirmed that the nanoparticles possess favorable imaging properties.Conclusions: This research demonstrates that the integration of PDA@Mn-siSur-c-NPs with PTT holds considerable therapeutic promise for improved breast cancer treatment.
研究领域:
纳米医学
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癌症治疗
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药物递送
·
分子成像
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光热治疗
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产品关联
DOI
PubMed
高影响因子
Medicinal Chemistry
·
2023
·Vol. 19
·期 3
·246-262
·
IF 2.3
Lu Jia-Hao,Lai Wu-Ji,Jiang Li-He,Lei Fu-Hou,Shen Li-Qun,Wu Ai-Qun
Survivin is an important member of the antiapoptotic protein family and controls the cell’s life cycle. Overexpression of survivin in tumor cells leads to inhibition of apoptosis, thus contributing to cancer cell proliferation. The largest binding pocket in the survivin dimer
was located in the BIR domain. The key to the efficacy of 3-cyanopyridines was their surface interaction with the survivin amino acid Ile74. Methods: Through the optimization of the 3-cyanopyridine, 29 new compounds with a 3- Cyanopyridine structure were designed, synthesized, and characterized
by NMR, IR, and mass spectrometry. The antitumor activity of the compounds in vitro was detected by the MTT method. Results: In vitro anti-tumor experiments showed that some compounds exhibited good anti-cancer effects. The IC50 values of the compound 2-amino-6-(2,4-difluorophenyl)-4-(4-hydroxyphenyl)
nicotinonitrile (10n) against human liver cancer (Huh7), human glioma (U251), and human melanoma (A375) cells were 5.9, 6.0 and 7.2 μM, respectively. The IC50 values of the compound 6-(2,4-difluorophenyl)- 4-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile
(9o) against Huh7, U251 and A375 cells were 2.4, 17.5 and 7.2 μM, respectively, which were better than those of 10- hydroxycamptothecin and 5-fluorouracil. Analysis of the results of molecular dynamics simulation established that the BIR domain is the optimal binding site on the survivin
protein, and the fingerprints of the eight most active compounds and the molecular docking to the survivin protein are analyzed. Conclusion: 3-Cyanopyridine is an excellent backbone for antitumor lead compounds, 10n and 9o, as derivatives of 3-Cyanopyridine are excellent survivin protein-targeting
inhibitors worthy of further study. The key factor in inhibiting survivin protein through the action of amino acid Ile74.
研究领域:
药理学
·
药物化学
·
癌症研究
·
分子生物学
·
药物设计
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Li Lihua,Chen Lingling,Huang Ling,Ye Xiangling,Lin Zefeng,Wei Xiaoming,Yang Xianfeng,Yang Zhongmin
Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO 3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO 3 , itself, could generate O 2 and CO 2 under H 2 O 2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO 3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.
研究领域:
纳米技术
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癌症研究
·
材料科学
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生物医学工程
·
药学
✓ 已验证
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2022
·
IF 4.885
Shiying Zeng,Qinglai Tang,Kang Jiang,Xiaojun Tang
Metformin (MET) and survivin siRNA were delivered using silk fibroin nanoparticles (SFNs) modified with polyethyleneimine (PEI). Nanoparticle functional groups, structural, stability and physicochemical characteristics of the nanoparticles were determined. SFNs loaded with siRNA that had appropriate size, zeta potential , and stability were confirmed by various analytical and spectroscopical methods. The vitro cytotoxicity analysis was performed using CNE2 nasopharyngeal carcinoma cells with different compositions, and the results showed that the newly fabricated nanoparticles effectively triggered apoptosis in CNE2. Afterward, the mice analysis was used to investigate the in vivo therapeutic efficacy. With no apparent weight loss, the co-delivery systems dramatically slowed nasopharyngeal tumor development in mice. Survivin siRNA and MET increased the number of apoptotic tumor cells on histopathology slides. Apoptosis induction in cancer cells and therapeutic effectiveness were satisfactory with the drug delivery method. In this way, it might be used as a therapeutic agent in the fight against nasopharyngeal cancer.
研究领域:
医学
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Nanomaterials
·
2017
·Vol. 7
·期 5
·110
·
IF 3.553
Zhuo Wu,Xiao-Lin Xu,Jun-Zhao Zhang,Xu-Hong Mao,Ming-Wei Xie,Zi-Liang Cheng,Lie-Jing Lu,Xiao-Hui Duan,Li-Ming Zhang,Jun Shen
Amylose is a promising nanocarrier for gene delivery in terms of its good biocompatibility and high transfection efficiency. Small interfering RNA against survivin (survivin-siRNA) can cause tumor apoptosis by silencing a hepatocellular carcinoma (HCC)-specific gene at the messenger RNA level. In this study, we developed a new class of folate-functionalized, superparamagnetic iron oxide (SPIO)-loaded cationic amylose nanoparticles to deliver survivin-siRNA to HCC cells. The cellular uptake of nanocomplexes, cytotoxicity, cell apoptosis, and gene suppression mediated by siRNA-complexed nanoparticles were tested. The results demonstrated that folate-functionalized, SPIO-loaded cationic amylose nanoparticles can mediate a specific and safe cellular uptake of survivin-siRNA with high transfection efficiency, resulting in a robust survivin gene downregulation in HCC cells. The biocompatible complex of cationic amylose could be used as an efficient, rapid, and safe gene delivery vector. Upon SPIO loading, it holds a great promise as a theranostic carrier for gene therapy of HCC.Keywords:amylose;small interfering RNA;magnetic resonance imaging;superparamagnetic iron oxide nanoparticles
研究领域:
纳米技术
·
基因治疗
·
癌症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Mengru Cai,Yu Yao,Dongge Yin,Rongyue Zhu,Tingting Fu,Jiahui Kong,Kaixin Wang,Jing Liu,Aina Yao,Yidan Ruan,Wenjuan Shi,Qian Zhu,Jian Ni,Xingbin Yin
In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named [email protected] @survivin [email protected] , [email protected] ) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the [email protected] with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the [email protected] in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of [email protected] , demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.
研究领域:
纳米技术
·
药学
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Zhongjuan Wang,Yueqin Liang,Yanqiu Liu,Hongying Xia,Jianqi Liu,Xingfang Jin,Zhongkun Li
Multi-drug resistance (MDR) is one of the major challenges in the successful chemotherapy of non-small cell lung cancer (NSCLC). Although RNA interference (RNAi) has been widely used to silence resistance-related genes, the effect remains unsatisfactory. In this study, we attempted to overcome MDR of NSCLC by simultaneously interfering with two RNAs that have different functions. A new pH-triggered polyglutamate brush polymer dimethylmaleic anhydride-poly(ethyleneglycol) monomethyl ether-b-polyglutamate-g-spermine (DMA-mPEG-b-PG-g-spermine, DPPGS) was designed and synthesized. The DPPGS/small interfering RNA (siRNA) complex nanoparticles (DPPGSN) were prepared. The results demonstrated that DPPGSN could be transformed from a negatively charged form into a positively charged form in the slightly acidic tumor extracellular environment. The siRNA targeting MDR1 mRNA (siMDR1) and siRNA targeting survivin mRNA (siSurvivin) could be efficiently co-delivered by DPPGS to simultaneously interfere with two genes (p < 0.01). Furthermore, DPPGS co-delivery of siMDR1 and siSurvivin lowered the IC50 value of cisplatin (DDP) in A549/DDP (p < 0.01) cells and increased the apoptosis rate of the cells (p < 0.01). Therefore, co-delivery of siMDR1 and siSurvivin using DPPGS would be a promising approach for overcoming MDR of NSCLC.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-13
·
IF 10.6
Zhang Lifeng,Luo Shihua,Li Wenbin,Su Wanting,Chen Siting,Liu Chunchen,Pan Weilun,Situ Bo,Zheng Lei,Li Ling,Yan Xiaohui,Zhang Ye
Rapid and sensitive nucleic acid detection is vital in disease diagnosis and therapeutic assessment. Herein, we propose a co-freezing localized CRISPR-Cas12a (CL-Cas12a) strategy for sensitive nucleic acid detection. The CL-Cas12a was obtained through a 15-minute co-freezing process, allowing the Cas12a/crRNA complex and hairpin reporter confined on the AuNPs surface with high load efficiency, for rapid sensing of nucleic acid with superior performance to other localized Cas12a strategies. This CL-Cas12a based platform could quantitatively detect targets down to 98 aM in 30 min with excellent specificity. Furthermore, the CL-Cas12a successful applied to detect human papillomavirus infection and human lung cancer-associated single-nucleotide mutations. We also achieved powerful signal amplification for imaging Survivin mRNA in living cells. These findings highlight the potential of CL-Cas12a as an effective tool for nucleic acid diagnostics and disease monitoring.Graphical abstract
研究领域:
生物技术
·
分子生物学
·
诊断学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 9
·1-10
·
IF 5.833
Xu Ping,Lu Chunwen,Wang Dahui,Fu Dong
An ultrathin micro-patterned MXene/PEDOT:PSS-based organic electrochemical transistor biosensor was constructed, which can significantly amplify the amperometric signal and transistor’s performance. A novel interdigitated OECTs biosensor has been developed for reliable determination of survivin for the following considerations: (1) The synergistic effect of intercalated MXene and ionic PEDOT:PSS enhanced the mobility and volumetric capacitance of OECTs biosensor. (2) Compared with the best previous literatures, our assay demonstrated enhanced detection limit of survivin down to 10 pg mL −1 , as well as satisfactory selectivity, reproducibility, and reliability. (3) Comparison of OECTs against commercial ELISA kit yielded favorable linearity ( Y = 1.0015* X + 0.0039) and correlation coefficient ( R 2 = 0.9717). Those advantages are expected to pave the way to design of an OECTs biosensor with robustness, non-invasiveness, and miniaturization for the point-of-care applications. Graphical abstract
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2017
·
IF 2.399
Lin Yu,Xiaofeng Wu,Min Chen,Huarong Huang,Yan He,Huaqian Wang,Dongli Li,Zhiyun Du,Kun Zhang,Susan Goodin,Xi Zheng
Background : Docetaxel is the first-line treatment for castration-resistant prostate cancer (CRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminishes its efficacy in high-dose monotherapy. YK-4-279 is a small molecule inhibitor of ETV1 that plays an important role in the progression of prostate cancer. The aim of this study was to evaluate the hypothesis that the combination of docetaxel and YK-4-279 will have a synergistic effect on inhibiting growth and accelerating apoptosis in human prostate cancer cells. Methods : Cell growth assessed using CCK-8 and trypan blue exclusion assays. Cell apoptosis was determined by morphological assessment in cells stained with propidium iodide. Standard scratch migration and Matrigel-coated transwell invasion assays were used to assess cell migration and invasion, respectively. Western blotting was used to investigate the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in prostate cancer cells. Results : The combination of low-dose docetaxel and YK-4-279 synergistically inhibited growth and induced apoptosis in human prostate cancer cells. The combination also more efficiently suppressed the migration and invasion of LNCaP and PC-3 cells. The combination of low-dose docetaxel and YK-4-279 caused a stronger decrease in the levels of ETV1, AR, PSA, p-STAT3, survivin, Bcl-2, and p-Akt in LNCaP cells and of p-Akt, Bcl-2, and p-STAT3 in PC-3 cells compared with either drug alone. Conclusions : These data suggest that the combination of docetaxel and YK-4-279 may be an effective approach for inhibiting the growth and metastasis of prostate cancer. This could permit a decrease in the docetaxel dose necessary for patients with CRPC and thereby lower its systemic toxicity.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Weipan Peng,Shenghui Li,Yating zhang,Qiuting Zhang,Wenna Li,Houyu Han,Dianming Zhou,Sheng Wang,Jin Chang,Xiaoqun Gong
Tumors progression is usually characterized by proliferation, migration, and angiogenesis , and it leads to uncontrolled tissue growth and blocks the mechanism of apoptosis. Therefore, targeted angiogenesis and anti-apoptosis is considered promising therapeutic strategy for cancer prevention and treatment. Herein, we report a versatile and intelligent MnO 2 -PEI-DNAzymes (MnPDs) nanodevice for self-sufficient anti-tumor angiogenesis and pro-apoptosis synergistic gene silencing, coupling multi-target bimodal in situ imaging. Intracellularly, the multifunctional charge-reversal MnPDs undergo reduction and lysis by the overexpressed GSH, actualizing enhanced MR imaging and sufficient DNAzyme cofactors in tumor tissue, and enabling miRNA-155 and telomerase biomarkers dual-fluorescence imaging. Under the precise multimodal imaging, the dual DNAzymes enable self-sufficient Early growth response-1 (EGR1) and Survivin (SUR) mRNAs synergistic silencing, effectively inhibiting tumor angiogenesis and anti-apoptotic. Considering that accurate and efficient therapy has become a trend in cancer therapy, our proposed self-sustaining multifunctional nanodevice is promising for broad clinical applications.
研究领域:
癌症生物学
·
纳米技术
·
基因治疗
·
分子成像
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 4
·3612-3625
·
IF 4.522
Liming Wang,Xin Zhang,Yang Liu,Shun Xu
The pivotal roles of long noncoding RNAs have been reported in various cancers. Recently, FBXL19-AS1 was proposed to be involved in tumor progression. However, its role in lung adenocarcinoma (LUAD) remains elusive. In this study, we observed that FBXL19-AS1 was significantly upregulated in LUAD tissues and high FBXL19-AS1 expression in LUAD was associated with a poor prognosis. Nevertheless, miR-203-3p showed the opposite effect. Moreover, cell viability and apoptosis analysis revealed that FBXL19-AS1 knockdown could arrest LUAD cells in G0/G1 phase and inhibit cell proliferation, migration and invasion in vitro and inhibited LUAD tumor progress in vivo. Mechanistically, we identified FBXL19-AS1 could act as a miR-203a-3p sponge using dual-luciferase reporter assay. In addition, we demonstrated that downregulation of miR-203a-3p reversed growth inhibition of LUAD cells caused by FBXL19-AS1 knockdown. Finally, FBXL19-AS1/miR-203a-3p axis was found to associate with baculoviral IAP repeat-containing protein 5.1-A-like (survivin), distal-less homeobox 5, E2F transcription factor 1, and zinc finger E-box binding homeobox 2 to regulate metastasis in LUAD cells. This study reveals a significance and mechanism of FBXL19-AS1 in LUAD proliferation and metastasis and offers a potential prognostic marker and a therapeutic target for patients with LUAD.
研究领域:
癌症生物学
·
分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）