Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Aihua Zou,Xiaotong Zhao,Ulrich A. Handge,Vasil M. Garamus,Regine Willumeit-Römer,Peihao Yin
Bufalin (BF), a traditional Chinese medicine, exhibited inhibitory activities against a broad spectrum of tumor cells. The present study elaborates that bufalin was successfully encapsulated into the cavity of β-cyclodextrin (β-CD), which was determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy ( 1 H NMR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The best reaction mole ratio of BF/β-CD was 1:5. The solubilities of bufalin in water and phosphate buffer solution (pH = 7.4) were increased up to 24 and 34 times after encapsulated into the cavity of β-CD respectively. The inclusion efficiency (IE) and drug loading (DL) of bufalin in the inclusion complex were (94.22 ± 0.85)% and (14.11 ± 0.20)%, respectively. Then β-CD conjugated with folic acid (FA) were further prepared and employed to improve the anti-tumor efficacy of inclusion complex. The in vitro dissolution and solubility study showed better values of inclusion complex and FA targeted inclusion complex than that of pure BF. Cytotoxicity experiments by using HCT116 cell line revealed that the antitumor efficiency of bufalin were enhanced more than two folds in the presence of β-CD and folate conjugated β-CD (FA-PEI-β-CD), which demonstrated the potential application of β-CD (FA-PEI-β-CD) as delivery vehicles of bufalin for antitumor therapy.
研究领域:
药学
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肿瘤学
·
生物化学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
·
IF 3.997
Yawen Li,Angelina Angelova,Jianwen Liu,Vasil M. Garamus,Na Li,Markus Drechsler,Yabin Gong,Aihua Zou
In this work, we used the small angle X-ray scattering (SAXS) method for controlled preparation of in situ forming sustained-release carriers for the antitumor drug bufalin (BUF), which has very poor solubility and a considerable cardiotoxicity in a non-encapsulated state. To that aim, we exploited the pseudo-ternary phase diagram of an oil(O)/surfactant(S)/water(W) system containing medium chain capric/caprylic triglycerides (MCT) and a co-surfactant blend of Macrogol (15)-hydroxystearate (Solutol HS 15) and sorbitan monooleate (Span 80). Two compositions with different oil contents (sample B and C) were selected from the microemulsion region of the phase diagram in order to study the effect of the aqueous environment on their structural behavior. A phase transition from a microemulsion (ME) to a liquid crystalline phase (LC) was established by SAXS upon progressive dilution. The drug bufalin (BUF) was encapsulated in the microemulsions with low viscosity, whereas the release of the drug occurred from the in situ generated lamellar liquid crystalline structures. The formulations were characterized by SAXS, dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM), rheology, drug loading and encapsulation efficiency, and in vitro release profiles. A correlation was suggested between the structures of the in situ phase-transition formed LC ME formulations, the differences in their viscosities and drug release profiles. The performed cytotoxicity, cell apoptosis and pharmacokinetic experiments showed an enhanced bioavailability of BUF after encapsulation. These results suggest potential clinical applications for the obtained safe in situ phase-transition sustained-release formulations of BUF.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Fei Wu,Chunxue Song,Hanxiao Yin,Ronglong Chen,Guanyu Huang,Jiajun Zhang,Haimin Chen,Li Lin,Junqiang Yin,Lisi Xie,Weihai Liu
Poor bioavailability and dose-limiting cardiotoxicity persistently hinder the clinical application of bufalin (BF). Conventional BF-based nanoagents have shown promise in tackling these challenges, yet advanced nanostrategies with further improved performance and clinical accessibility still await development. Herein, we introduce a novel cooperative nanoparadigm based on disulfide-linked bufalin homodimeric prodrugs (SBF) and metal phenolic networks (MPNs). This strategy achieves high drug-loading capacity and structural stability. Stability perturbation experiments reveal that hydrophobic interactions, electrostatic adsorption, and coordination bonds synergistically drive co-assembly of SBF and MPNs. The resultant nanopartieles (MSBNAs) exhibit prolonged circulation kinetics, tumor-selective accumulation, and pH/GSH dual-responsive properties, effectively mitigating BF-induced cardiotoxicity. Further antitumor mechanistic investigations unveil that MSBNAs amplify BF-induced ferroptosis through a dual assault of oxidative stress and iron overload induced jointly by MPNs-delivered exogenous iron and BF-triggered endogenous iron. This increased ferroptosis endows MSBNAs with superior suppression of tumor growth and lung metastasis, maintaining excellent biocompatibility without cardiotoxicity. Our work not only establishes a promising candidate platform to surmount the therapeutic hurdles of BF but also enriches the design landscapes of co-assembled nanomedicines, thereby laying a foundation for the clinical translation of BF and other antitumor drugs.
研究领域:
药学
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纳米医学
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肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Hairong Zeng,Chao Xia,Bei Zhao,Mengmeng Zhu,HaoYue Zhang,Die Zhang,Xin Rui,Huili Li,Yi Yuan
Bufalin (Buf), an active ingredient of the traditional Chinese medicine Chansu, is known to have anticancer effects for breast cancer. However, its poor solubility, high toxicity, and extensive side effects limit its use. Metal-organic frameworks (MOFs) are a class of promising drug delivery systems known for their high porosity. Here, we designed and constructed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of Buf (FA-MOF/Buf). Moreover, the anticancer activity of nanomedicines was also explored in vitro and in vivo . Compared to free Buf, the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro . Furthermore, it displayed improved accumulation in the tumor site, enhanced anticancer activity, and reduced side effects in vivo . Our results demonstrated that FA-MOF could be developed as a potential delivery system for Buf to improve its antitumor activity for breast cancer treatment.
研究领域:
药理学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2023
·
IF 24.3
Wei Zhang,Yibao Fan,Jinze Zhang,Dan Shi,Jiahui Yuan,Milad Ashrafizadeh,Wei Li,Man Hu,A.M. Abd El-Aty,Ahmet Hacimuftuoglu,Michael Linnebacher,Yongxian Cheng,Weiguang Li,Shuo Fang,Peng Gong,Xianbin Zhang
Aims Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer. Methods The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo . Results CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX . Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells. Conclusions Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.
研究领域:
肿瘤学
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药学
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分子生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yichen Liu,Dahai Hou,Hui Wang,Qiuying Yan,Yunzhu Xu,Qibiao Wu,Dan Dong,Weixing Shen,Weiwei Tao,Haibo Cheng,Dongdong Sun
Colorectal cancer, a highly invasive malignancy, poses significant treatment challenges due to the immunosuppressive tumor microenvironment. Tumor-associated macrophages, which primarily exhibit the M2 phenotype, play a key role in cancer progression and immune evasion. Reprogramming these M2 macrophages to the tumor-suppressive M1 phenotype represents a promising therapeutic approach to enhance antitumor immunity. In this study, we developed a calcium lactate nanoparticle-based delivery system (CLBRP) to codeliver bufalin, a potent Na + /K + -ATPase inhibitor with anticancer properties, and CRISPR-Cas9, which targets the immune checkpoint CD47. The system releases its payload under low pH conditions typical of the tumor microenvironment, increasing extracellular Ca 2+ and intracellular osmotic pressure, thereby inducing pyroptosis and immunogenic cell death. Bufalin induces cancer cell apoptosis, inhibits Na + /K + -ATPase, and triggers pyroptosis, which activates a strong immune response. Additionally, bufalin and D-lactic acid synergistically promote macrophage repolarization to the M1 phenotype. CRISPR-Cas9-mediated editing of the CD47 gene on tumor cells blocks antiphagocytic signals, enhancing M1 macrophage phagocytosis and increasing the antitumor immune response. This multimodal strategy triggers strong local antitumor effects and controls metastatic lesions via systemic immune activation, demonstrating significant potential for colorectal cancer treatment. Furthermore, this approach offers a new direction for overcoming resistance to immunotherapies and improving clinical outcomes.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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基因编辑
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癌症生物学
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肿瘤微环境
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Ying Xu,Yulong Liu,Qi Liu,Shengzhe Lu,Xiaolin Chen,Wenrong Xu,Feng Shi
Albumin nanoparticles represent an approved anti-tumor drug delivery system . However, there is only one albumin nanoparticle product (paclitaxel-albumin nanoparticle) on the market. The application of albumin carriers is limited by the lack of universal preparation technology and insufficient targeting effect. Herein, we developed multifunctional albumin sub-microspheres prepared by coaxial-electrospray technology to co-delivery bufalin and nintedanib for tumor-targeted combination therapy. The biguanide and ursodeoxycholic acid dual-modified multifunctional albumin was synthesized to enhance the anti-tumor effect and tumor target efficiency. Coaxial-electrospray technology was utilized in preparing albumin sub-microspheres with a core-shell structure that enables payload efficiency and stability. More importantly, the in vitro and in vivo experiments demonstrated that the multifunctional albumin sub-microspheres possessed superior tumor target efficiency. Furthermore, nintedanib and bufalin combined therapy relieved the tumor microenvironment and exerted a synergistic therapeutic effect. Therefore, this work provides a novel method for fabricating an albumin-based drug delivery system and a potential efficient combination therapeutic strategy for tumor treatment.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2024
·Vol. 23
·期 1
·1-12
·
IF 3.9
Fan Yibao,Zhang Wei,Iqbal Zoya,Li Xinxin,Lin Zhiyin,Wu Zhuolin,Li Qianyou,Dong Hongxia,Zhang Xianbin,Gong Peng,Liu Peng
Background Bufalin (BA) is a potent traditional Chinese medicine derived from toad venom. It has shown significant antitumor activity, but its use is limited by cardiotoxicity, which necessitates innovative delivery methods, such as rod-shaped mesoporous silica nanoparticles (rMSNs). rMSNs have been extensively employed for reducing drug toxicity and for controlled or targeted drug delivery in tumor therapy. However, their potential in delivering BA has not been completely elucidated. Therefore, in this study, BA-loaded rMSNs (BA-rMSNs) were developed to investigate their potential and mechanism in impairing colon cancer cells.Methods rMSNs were developed via the sol‒gel method. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the rMSN in loading BA. The antiproliferative activities of the BA-rMSNs were investigated via 5-ethynyl-2’-deoxyuridine and CCK-8. To evaluate cell death, Annexin V-APC/PI apoptotic and calcein-AM/PI double staining were performed. Western blotting, oil red O staining, and Nile red solution were employed to determine the ability of BA-rMSNs to regulate lipophagy.Results The diameter of the BA-rMSNs was approximately 60 nm. In vitro studies demonstrated that BA-rMSNs markedly inhibited HCT 116 and HT-29 cell proliferation and induced cell death. In vivo studies revealed that BA-rMSNs reduced BA-mediated cardiotoxicity and enhanced BA tumor targeting. Mechanistic studies revealed that BA-rMSNs blocked lipophagy.Conclusion srMSNs reduced BA-mediated cardiotoxicity and impaired the growth of colon cancer cells. Mechanistically, antitumor activity depends on lipophagy.
研究领域:
药学
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纳米技术
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2022
·
IF 3.915
Yujia Liu,Xiaoyu Lu,Zhenhai Zhang,Shulong Jiang,Huixia Lv
In this study, amphiphilic block copolymer mPEG-cholic acid was synthesized in conjunction with TPGS as stabilizer to prepare multifunctional micelles. The formed polymeric micelles (PCTm) were used for the delivery of paclitaxel (PTX) and bufalin (BF). PEG group could enhance solubility and extend circulation time, while cholic acid groups achieved the liver targeted function. Combinations of these approaches could realize a synergistic therapeutic effect in the treatment of advanced hepatocellular carcinoma. CLSM in vitro results demonstrated that drug capsulation into PCTm could enhance cellular uptake. FCM results confirmed the uptake amount of C6/PCTm was 7.5-fold higher than that of free C6 after incubation for 2 h. Competitive inhibition test proved the Na+-taurocholate co-transporting polypeptide (NTCP) involved in the uptake mechanism of PCTm. Meanwhile, in vivo imaging assays demonstrated that the fluorescence intensity of Cy5.5/PCTm was higher than that of free Cy5.5 on liver and tumor with extended circulation time to 48 h. In addition, in vivo studies confirmed that the combined therapy exhibited the strongest tumor inhibition rate of 82.29% with lower systemic toxicity. Hence, these results indicated that PCTm could provide a promising strategy for targeting hepatocellular carcinoma and achieve the goal of synergism and attenuation.
研究领域:
药学
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癌症研究
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2026
·Vol. 87
·期 2
·e70236
·
IF 4.2
Chenghua Wu,Xiaobin Zhuo,Jianxin Yang,Yuxiao Tang,Weili Wang,Mengpu Wu,Gen Miao,Chenqi Li,Hui Shen,Jianxin Qian,Dongyao Wang
Inhibiting the malignant proliferation is crucial for managing the cancer progression. NCAPG (Non-SMC condensin I complex subunit G) is a main component in cell proliferation, which is highly expressed in liver tumors and negatively correlated with the overall survival of hepatocellular carcinoma (HCC) patients. In this study, we identified bufalin as a molecular glue for the first time that specifically degraded NCAPG by coupling it to cathepsin V (CTSV). Distinguished from traditional PROTACs, bufalin served as a molecular glue with the distinct advantages of a smaller molecular weight and superior bioavailability. This degradation inhibited the proliferation of HCC cells by inducing G2/M phase cell cycle arrest at low doses (20–40 nM), but did not trigger the apoptosis signaling. Using co-immunoprecipitation and confocal microscopy, we confirmed the interaction between CTSV and NCAPG by bufalin. Knockdown of CTSV or NCAPG attenuated the anti-proliferation effects of bufalin in HCC cells. Cell cycle analysis also showed significantly reduced G2/M arrest in knockdown cells. The downstream proliferation regulators Cyclin D1 and CDK1 were also regulated by bufalin in a CTSV/NCAPG-dependent manner. Our study not only identified the CTSV-NCAPG complex as a novel therapeutic target but also discovered a potential molecular glue, bufalin, which exerts anti-proliferation effects through cell cycle regulation. These findings highlight the potential clinical translational value of bufalin as a promising, bioavailable therapeutic agent for the targeted treatment of liver cancer.
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PubMed
高影响因子
Nano Research
·
2021
·Vol. 14
·期 11
·3988-3998
·
IF 8.897
He Jiaqi,Chen Guoqin,Zhao Peng,Ou Caiwen
Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm −2 ), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on 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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材料科学
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产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2021
·Vol. 22
·期 4
·1-13
·
IF 3.246
Xu Ying,Tang Lei,Chen Peng,Chen Mei,Zheng Miaomiao,Shi Feng,Wang Yanchun
A novel albumin polymer hybrid with a core–shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n -butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein–PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.
研究领域:
药学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
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