Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 4
·527-542
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IF 2.9
Yan Zi-Jun,Wu Xiao-Ping,Wei Pan-Pan,Deng Meng-Yue,Yang Kun,Zhang Liang-Ming,Ding Yu-Zhen,Xia Die,Ma Bing-Suo,Zhang Lei,Yuan Xiao-Yan,Chen Tong
Novel antitumor drugs and nano-delivery systems for treating liver cancer are becoming a research hotspot, given that the incidence and mortality rates of liver cancer are high. Herein, nanoemulsion hybrid lipid carriers containing norcantharidin (Nor) (NNHLCs) were first prepared by
loading water-in-oil nanoemulsions into hybrid solid lipids using nanoemulsion-thin film ultrasonic dispersion method. The in vitro and in vivo kinetic features were determined by in situ unidirectional perfusion and plasma concentration-time curve method, respectively.
The activity of NNHLCs against liver cancer HepG2 cells was determined by evaluating in vitro cytotoxicity, clone formation, apoptosis, and cell cycle experiments. Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) results
indicated that Nor exists in NNHLCs in an amorphous state with good encapsulation in the lipid matrix. The absorptive constants and permeabilities of NNHLCs were significantly increased compared with Nor. The relative bioavailability of NNHLCs to Nor was 207.68%. NNHLCs could inhibit the viability
and proliferation of HepG2 cells and promote apoptosis. Thus, nanoemulsion hybrid lipid carriers may provide a new option for the efficient delivery of chemotherapeutic drugs.
研究领域:
药剂学
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肿瘤学
·
纳米技术
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DOI
高影响因子
Journal of Nanomaterials
·
2019
·
IF 2.233
Youxiang Xiong,Hongxia Tang,Wenhong Liu,Tingting Zhang,Rui Ma,Chaofeng Mu,Zhihong Zhu,Fanzhu Li
The objective of this study was to construct norcantharidin (NCTD)/tetrandrine (Tet) dual-drug loaded lipid nanoparticles (FA-LP@Tet/(MSNs@NCTD)) based on mesoporous silica nanoparticles (MSNs) for controlling drug release and lowering their systemic toxicity. In this study, MSNs were prepared and used for encapsulating anticancer drug NCTD; then MSNs@NCTD and Tet were loaded into liposomes to construct dual-drug loaded lipid nanoparticles with folic acid (FA) as the targeting moiety. The prepared dual-drug loaded lipid nanoparticles with a uniform particle size distribution of (PDI , zeta potential -), had a visible core-shell structure under transmission electron microscopy; the encapsulation efficiency of NCTD and Tet was 86.62% and 79.19%, respectively, with obvious in vitro sustained release characteristics. The cellular uptake results suggested that FA modification could enhance intracellular distribution of FA-LP@Tet/(MSNs@NCTD). Furthermore, cell apoptosis assays showed FA-LP@Tet/(MSNs@NCTD) had better antitumor ability via reversing multidrug resistance. Therefore, FA-LP@Tet/(MSNs@NCTD) was a promising drug delivery system for combination cancer therapy.
研究领域:
药学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Xiaofen Xu,Yanggong Li,Feihu Wang,Li Lv,Jieying Liu,Mingna Li,Aijie Guo,Jinjun Jiang,Yuanyuan Shen,Shengrong Guo
New norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives (NCTD-HACCs) were synthesized and characterized by 1 H NMR, Fourier-transform infrared spectroscopy (FT-IR), and wide-angle X-ray diffraction (WAXD). Two NCTD-HACCs with different degrees of substitution ( DS ) (12.2% and 24.8%) were obtained, which had good water solubility. NCTD was released from the NCTD-HACCs via hydrolysis, faster in pH 5.0 than pH 7.4 and presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. Fluorescence microscope and flow cytometry analysis demonstrated that the NCTD-HACC was endocytosized into MGC80-3 cells and the uptaken amount increased as incubation time . Compared with free NCTD, the NCTD-HACCs showed lower in vitro anti-tumor activity against human gastric cancer MGC80-3 cells, but higher in vivo tumor growth inhibition in S180 tumor-bearing mice. The in vivo near-infrared (NIR) fluorescence real-time imaging result showed the fluorescence intensity in tumor was much higher than that in heart, liver, spleen and lung (except kidney) after i.v. injection of the FITC-labeled NCTD-HACC2, indicating specific accumulation of the NCTD-HACC in tumor.
研究领域:
药学
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生物技术
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癌症研究
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材料科学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2021
·
IF 4.939
Leyi Liang,Ling Zhao,Ying Wang,Yan Wang
Mesenchymal stem cell-derived exosomes (MSC-Exos) have potential as drug-delivery vehicles and exhibit great promise for hepatocellular carcinoma (HCC) therapy. Here, we consider bone mesenchymal stem cell-derived exosomes (BMSC-Exos) as drug carriers to encase anticancer drug norcantharidin (NCTD) and explore their potential therapeutic effects against HCC. NCTD was loaded into purified exosomes from BMSCs via electroporation, and an in vitro drug release study showed that BMSC-Exos–NCTD provided a continuous and slow release of the drug. A series of in vitro and in vivo pharmacodynamic evaluations based on the HCC cell line HepG2 were conducted. The results showed that the BMSC-Exos–NCTD delivery system effectively promoted cellular uptake, induced cell cycle arrest, reduced tumor cell proliferation, increased apoptosis, and exerted obvious in vivo antitumor effects compared with the NCTD treatment alone, with BMSC-Exos–NCTD showing more significant antitumor effects. Furthermore, the in vivo detection results of the homing effect using the probe Cy5.5 showed that the BMSC-Exos carrier has an in situ homing effect on the tumor sites of HCC in mice. Moreover, BMSC-Exos–NCTD did not show body toxicity. Excitedly, BMSC-Exos–NCTD repaired damaged liver tissues in liver sections; specifically, the experimental effectiveness of the exosomes on the normal liver cell line L02 indicated that the damaged liver cells were repaired by the exosomes, as reflected by the increase in cellular proliferation and the inhibition of liver cell oxidation. Our results suggest that BMSC-Exos, as drug carriers with specific functions, have great potential in the HCC treatment in combination with anticancer drugs.
研究领域:
肿瘤学
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药学
·
干细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Shulong Jiang,Mengying Li,Ying Hu,Zhenhai Zhang,Huixia Lv
A polymer of Galactosamine-hyaluronic acid-Vitamin E succinate (Gal-HA-VES) was designed to prepare multifunctional self-assembled micelles for delivery of Norcantharidin (NCTD) to Hepatic carcinoma. NCTD/Gal-HA-VES showed higher cytotoxicity toward CD44-overexpressing MCF-7 cells, MCF-7/Adr cells and ASGP-R overexpressing HepG2 cells, consistent with the enhanced cellular uptake in the selected cell models, indicating Gal-HA-VES micelles were taken up in MCF-7 and HepG2 cells by CD44 and ASGPR receptor mediated endocytosis, respectively. Moreover, the accumulation of Rhodamine 123 demonstrated that Gal-HA-VES has the same action of TPGS as a P -glycoprotein inhibitor blocked drug efflux-related MDR mechanism in resistant MCF-7/Adr cells. The Cell apoptosis assays indicated that NCTD/Gal-HA-VES were more effective in triggering apoptosis, compared with free NCTD or NCTD/HA-VES groups. In vivo study demonstrated that NCTD/Gal-HA-VES group exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. Hence NCTD/Gal-HA-VES micelles system can achieve significant tumor targeting and effective treatment of hepatic carcinoma.
研究领域:
药学
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癌症研究
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生物医学工程
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Peng-Wei Chen,Yu-Meng Zhang,Lin-Song Li,Bang-Bang Liu,Han-Lu Sun,Liping Chen,Xiaojing Yang,Mei-Xia Zhao
The combination of phototherapy with oxaliplatin (OXA) represents a potent strategy for triggering immunogenic cell death (ICD) and elicit robust antitumor immunity. In this study, we construct IROTD nanoparticles (IROTD NPs) through self-assembly of a norcantharidin (NCTD)-OXA-conjugated polymer (P2) and the near-infrared (NIR) photosensitizer DTIR780. Under 808 nm laser irradiation, IROTD NPs generate heat and reactive oxygen species (ROS) while release OXA and NCTD, result in severe DNA damage and potent induction of ICD within tumor cells. Concurrently, NCTD inhibits DNA repair mechanisms and down-regulates PD-L1expression, thereby increase the infiltration of cytotoxic T-cell and amplify systemic antitumor immunity. Leverage the enhanced permeability and retention (EPR) effect, IROTD NPs efficiently accumulate at tumor sites, result in remarkable inhibition of tumor growth and recruitment of CD4 + and CD8 + T lymphocytes, which collectively contribute to the activation of a systemic antitumor immunity. In a bilateral tumor model, IROTD NPs effectively inhibit both primary and distant tumor growth. Overall, this work presents a rationally designed combinatorial nanoplatform that effectively ignites systemic immune response, thus establish a prospective chemo-immunotherapeutic stratagem for cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Mingli Wei,Ying Jiang,Rong Sun,Liangyi Fang,Chenxiao Chu,Haibing He,Jingxin Gou,Tian Yin,Yongbo Song,Xing Tang,Fan Zhao,Yinglei Zhai,Yu Zhang
Combination chemotherapy has been proved to be an effective strategy in the clinic, and nanoformulations have drawn much attention in the field of drug delivery. However, conventional nanocarriers suffer from shortcomings such as inefficient coloading and undesired molar ratios of the combined drugs, preleakage of cargos during systemic circulation, and lack of cancer-selective drug release. To achieve tumor-specific codelivery of cisplatin (CDDP) and norcantharidin (NCTD) for synergistic treatment of liver cancer, a novel linear–dendritic polymer, termed as G1(PPDC)x, was designed and synthesized, where a prodrug consisting of cisplatin (CDDP) and norcantharidin (NCTD) was conjugated to PEG2000 via ester bonds to fabricate linear polymer–drug conjugates, and the conjugates were subsequently grafted to the terminal hydroxyls of a dendritic polycarbonate core. Benefiting from the hydrogen bond interactions, G1(PPDC)x could spontaneously self-assemble into a unique type of raspberry-like multimicelle clusters in solution (G1(PPDC)x-PMs). G1(PPDC)x-PMs possessed an optimal synergistic ratio of CDDP and NCTD, without obvious premature release or disassembly in biological environments. Intriguingly, upon extravasation into the interstitial tumor tissues, G1(PPDC)x-PMs (132 nm in diameter) could disassemble and reassemble into smaller micelles (40 nm in diameter) in response to the mildly acidic tumor microenvironment, which would enhance the deep tumor penetration and cellular accumulation of drugs. In vivo delivery of G1(PPDC)x-PMs led to a significantly prolonged blood circulation half-life, which is beneficial to achieve sufficient tumor accumulation through the enhanced permeability and retention (EPR) effect. G1(PPDC)x-PMs displayed the best antitumor activity in H22 tumor-bearing mice with a tumor inhibition rate of 78.87%. Meanwhile, G1(PPDC)x-PMs alleviated both myelosuppression toxicities of CDDP and vascular irritation of NCTD. Our results demonstrated that G1(PPDC)x-PMs could serve as an effective drug delivery system for codelivery of CDDP and NCTD to treat liver cancer efficiently.
研究领域:
药学
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-26
·
IF 12.6
Zhao Feng,Gong Liming,Wang Ping,Chen Dong,Cao Shijie,Yang Feifei,Tang Manqing,Meng Yuanyuan,Wang Yuming,Miao Lin,Li Yunfei,Huang Wei
In the absence of tumor antigen specificity, direct chemokine administration carries the risk of significant “on-target, off-tumor” toxicities, highlighting the need for small-molecule approaches with reduced immunogenicity. This study investigates the synergistic potential of norcantharidin (NCTD) and lomitapide (lomi) in selectively restoring CCL4 expression by deactivating the tumor intrinsic β-catenin pathway. Due to its similar lipophilicity to lomi and potential to suppress β-catenin, NCTD prodrug (C12) was selected to be co-encapsulated with lomi in a nanoparticle-mediated co-delivery system (NP“C12 + lomi”). The NP“C12 + lomi” formulation exhibited a high encapsulation rate, uniform particle size, and suitability for therapeutic use. It effectively inhibited the proliferation of 4T1 cells and restored CCL4 expression. In both primary breast tumor and surgically resected tumor mouse models, NP“C12 + lomi” significantly increased the proportion of CD8 + cells in primary tumors, blood, and lung metastases, approximately doubling their presence. This led to a prolongation of median survival in mice to 59 days. Furthermore, when combined with an immune checkpoint inhibitor, NP“C12 + lomi” substantially inhibited tumor growth and lung metastasis without affecting body weight or causing major tissue or organ damage. This was attributed to the controlled dissociation of the nanoparticle and the subsequent modulation of C12 and lomi, which mitigated CCL4-related toxicity. This study provides valuable insights into the safe production of chemokines using a small-molecule pair through a nanosystem and presents a robust chemo-immunological cascade therapy strategy, demonstrating significant efficacy against malignant metastatic tumors. Graphical abstract
研究领域:
肿瘤学
·
免疫学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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