Turn off MathJax
Article Contents
Binlong Chen, Yanzhong Zhao, Zichang Lin, Jiahao Liang, Jialong Fan, Yanyan Huang, Leye He, Bin Liu. Apatinib and gamabufotalin co-loaded lipid/prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2023.11.011
Citation: Binlong Chen, Yanzhong Zhao, Zichang Lin, Jiahao Liang, Jialong Fan, Yanyan Huang, Leye He, Bin Liu. Apatinib and gamabufotalin co-loaded lipid/prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2023.11.011

Apatinib and gamabufotalin co-loaded lipid/prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis

doi: 10.1016/j.jpha.2023.11.011

This work was partially supported by Changsha Municipal Natural Science Foundation (kq2014265), The Construction Program of Hunan’s innovative Province (CN)-High-tech Industry Science and Technology Innovation Leading Project (2020SK2002), The Natural Science Foundation of Hunan Province (2023JJ40130), Postgraduate Scientific Research Innovation Project of Hunan Province (CX20230317), The Changsha Platform and Talent Plan (kq2203002).

  • Received Date: Sep. 14, 2023
  • Accepted Date: Nov. 21, 2023
  • Rev Recd Date: Nov. 09, 2023
  • Available Online: Nov. 30, 2023
  • Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects, as well. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating VEGFR and MMP-9. In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.
  • loading
  • E.C. Smyth, M. Nilsson, H.I. Grabsch, et al., Gastric cancer, Lancet. 396 (2020) 635-648.
    F.M. Johnston, M. Beckman, Updates on management of gastric cancer, Curr. Oncol. Rep. 21 (2019), 67.
    N. Charalampakis, P. Economopoulou, I. Kotsantis, et al., Medical management of gastric cancer: a 2017 update, Cancer Med. 7 (2018) 123-133.
    Y.Y. Choi, J.H. Cheong, Beyond precision surgery: Molecularly motivated precision care for gastric cancer, Eur. J. Surg. Oncol. 43 (2017) 856-864.
    J. Ding, X. Chen, X. Dai, et al., Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 895-896 (2012) 108-115.
    J. Li, X. Zhao, L. Chen, et al., Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies, BMC Cancer. 10 (2010), 529.
    S. Tian, H. Quan, C. Xie, et al., YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo, Cancer Sci. 102 (2011) 1374-1380.
    R. Geng, L. Song, J. Li, et al., The safety of apatinib for the treatment of gastric cancer, Expert Opin. Drug Saf. 17 (2018) 1145-1150.
    G. Roviello, A. Ravelli, K. Polom, et al., Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer, Cancer Lett. 372 (2016) 187-191.
    J. Ding, X. Chen, Z. Gao, et al., Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans, Drug Metab. Dispos. 41 (2013) 1195-1210.
    J.A. Ajani, T.A. D'Amico, D.J. Bentrem, et al., Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology, J. Natl. Compr. Canc. Netw. 20 (2022) 167-192.
    N. Tang, L. Shi, Z. Yu, et al., Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway, Oncotarget. 7 (2016) 3533-3547.
    Y.B.L. Moreno, A. Katz, W. Miklos, et al., Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+-ATPase, Mol. Cancer. 12 (2013), 33.
    J. Fan, B. Liu, Y. Long, et al., Sequentially-targeted biomimetic nano drug system for triple-negative breast cancer ablation and lung metastasis inhibition, Acta Biomater. 113 (2020) 554-569.
    B. Yuan, R. Shimada, K. Xu, et al., Multiple cytotoxic effects of gamabufotalin against human glioblastoma cell line U-87, Chem. Biol. Interact. 314 (2019), 108849.
    S. Nagini, Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention, World J. Gastrointest. Oncol. 4 (2012) 156-169.
    H. Wong, T. Yau, Targeted therapy in the management of advanced gastric cancer: Are we making progress in the era of personalized medicine?, Oncologist. 17 (2012) 346-358.
    Y. Ke, J. Zhu, Y. Chu, et al., Bifunctional fusion membrane-based hydrogel enhances antitumor potency of autologous cancer vaccines by activating dendritic cells, Advanced Functional Materials. 32 (2022), 2201306.
    Q. Liu, D. Zhang, H. Qian, et al., Superior antitumor efficacy of IFN-alpha2b-incorporated photo-cross-linked hydrogels combined with T cell transfer and low-dose irradiation against gastric cancer, Int. J. Nanomedicine. 15 (2020) 3669-3680.
    D. Zhang, Y. Chu, H. Qian, et al., Antitumor activity of thermosensitive hydrogels packaging gambogic acid nanoparticles and tumor-penetrating peptide iRGD against gastric cancer, Int. J. Nanomedicine. 15 (2020) 735-747.
    W. Chen, K. Shi, J. Liu, et al., Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer, Bioact. Mater. 23 (2023) 1-15.
    X. Cai, W. Gao, M. Ma, et al., A prussian blue-based core-shell hollow-structured mesoporous nanoparticle as a smart theranostic agent with ultrahigh pH-responsive longitudinal relaxivity, Adv. Mater. 27 (2015) 6382-6389.
    J. Liang, C. Wang, J. Fan, et al., Hybrid membrane-camouflaged hollow prussian blue nanoparticles for shikonin loading and combined chemo/photothermal therapy of metastatic TNBC, Materials Today Advances. 14 (2022), 100245.
    C. Tong, X. Zhong, Y. Yang, et al., PB@PDA@Ag nanosystem for synergistically eradicating MRSA and accelerating diabetic wound healing assisted with laser irradiation, Biomaterials. 243 (2020), 119936.
    B. Liu, W. Wang, J. Fan, et al., RBC membrane camouflaged prussian blue nanoparticles for gamabutolin loading and combined chemo/photothermal therapy of breast cancer, Biomaterials. 217 (2019), 119301.
    C. Xiao, C. Tong, J. Fan, et al., Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation, J. Control. Release. 339 (2021) 259-273.
    E. Sackmann, Supported membranes: scientific and practical applications, Science. 271 (1996) 43-48.
    R.H. Tammi, A. Kultti, V.M. Kosma, et al., Hyaluronan in human tumors: pathobiological and prognostic messages from cell-associated and stromal hyaluronan, Semin. Cancer Biol. 18 (2008) 288-295.
    A. Ianevski, A.K. Giri, T. Aittokallio, SynergyFinder 2.0: visual analytics of multi-drug combination synergies, Nucleic Acids Res. 48 (2020) W488-W493.
    H. Meng, M. Wang, H. Liu, et al., Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice, ACS Nano. 9 (2015) 3540-3557.
    H. Zhou, P. You, H. Liu, et al., Artemisinin and Procyanidins loaded multifunctional nanocomplexes alleviate atherosclerosis via simultaneously modulating lipid influx and cholesterol efflux, J. Control. Release. 341 (2022) 828-843.
    Y. Long, Z. Wang, J. Fan, et al., A hybrid membrane coating nanodrug system against gastric cancer via the VEGFR2/STAT3 signaling pathway, J. Mater. Chem. B. 9 (2021) 3838-3855.
    Q. Xie, B. Li, J. Fan, et al., Biomimetic hybrid-cell membrane nanoparticles loaded with panaxytriol for breast cancer combinational therapy, Materials & Design. 223 (2022), 111219.
    Z. Lei, J. Fan, X. Li, et al., Biomimetic graphene oxide quantum dots nanoparticles targeted photothermal-chemotherapy for gastric cancer, J. Drug Target. 31 (2023) 320-333.
    J. Fan, Y. Qin, C. Xiao, et al., Biomimetic PLGA-based nanocomplexes for improved tumor penetration to enhance chemo-photodynamic therapy against metastasis of TNBC, Materials Today Advances. 16 (2022), 100289.
    J.R. Casey, S. Grinstein, J. Orlowski, Sensors and regulators of intracellular pH, Nat. Rev. Mol. Cell Biol. 11 (2010) 50-61.
    G. Liu, X. Zhao, Y. Zhang, et al., Engineering biomimetic platesomes for pH-responsive drug delivery and enhanced antitumor activity, Adv. Mater. 31 (2019), 1900795.
    T.M. Allen, P.R. Cullis, Liposomal drug delivery systems: from concept to clinical applications, Adv. Drug Deliv. Rev. 65 (2013) 36-48.
    L.J. Deng, Y. Li, M. Qi, et al., Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment, Eur. J. Pharmacol. 887 (2020), 173379.
    W. Muller, T. Noguchi, H.C. Wirtz, et al., Expression of cell-cycle regulatory proteins cyclin D1, cyclin E, and their inhibitor p21 WAF1/CIP1 in gastric cancer, J. Pathol. 189 (1999) 186-193.
    A. Dongre, R.A. Weinberg, New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer, Nat. Rev. Mol. Cell Biol. 20 (2019) 69-84.
    Z. Yu, W. Guo, X. Ma, et al., Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells, Mol. Cancer. 13 (2014), 203.
    Q. Zhang, C. Deng, Y. Fu, et al., Repeated administration of hyaluronic acid coated liposomes with improved pharmacokinetics and reduced immune response, Mol. Pharm. 13 (2016) 1800-1808.
    A. Schroeder, D.A. Heller, M.M. Winslow, et al., Treating metastatic cancer with nanotechnology, Nat. Rev. Cancer. 12 (2011) 39-50.
    D.X. Nguyen, P.D. Bos, J. Massague, Metastasis: from dissemination to organ-specific colonization, Nat. Rev. Cancer. 9 (2009) 274-284.
    Z. Zhang, B. Niu, J. Chen, et al., The use of lipid-coated nanodiamond to improve bioavailability and efficacy of sorafenib in resisting metastasis of gastric cancer, Biomaterials. 35 (2014) 4565-4572.
    J. Wolfram, M. Zhu, Y. Yang, et al., Safety of nanoparticles in medicine, Curr. Drug Targets. 16 (2015) 1671-1681.
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (94) PDF downloads(10) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint