Apatinib and Gamabufotalin Co-loaded Lipid/Prussian Blue Nanoparticles for Synergistic Therapy to Gastric Cancer with Metastasis

Overview

Journal J Pharm Anal

Specialty Chemistry

Date 2024 May 23

PMID 38779391

Authors

Binlong Chen

Yanzhong Zhao

Zichang Lin

Jiahao Liang

Jialong Fan

Yanyan Huang

Leye He

Bin Liu

Affiliations

Soon will be listed here.

Abstract

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. 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. assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). 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.

Citing Articles

Advances on Delivery System of Active Ingredients of Dried Toad Skin and Toad Venom.

Zhang D, Zhai B, Sun J, Cheng J, Zhang X, Guo D Int J Nanomedicine. 2024; 19:7273-7305.

PMID: 39050871 PMC: 11268768. DOI: 10.2147/IJN.S469742.

Parkin deficiency promotes liver cancer metastasis by TMEFF1 transcription activation via TGF-β/Smad2/3 pathway.

Su Q, Wang J, Ren J, Wu Q, Chen K, Tu K Acta Pharmacol Sin. 2024; 45(7):1520-1529.

PMID: 38519646 PMC: 11192956. DOI: 10.1038/s41401-024-01254-3.

References

Tang N, Shi L, Yu Z, Dong P, Wang C, Huo X . Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway. Oncotarget. 2015; 7(3):3533-47. PMC: 4823125. DOI: 10.18632/oncotarget.6514. View

Roviello G, Ravelli A, Polom K, Petrioli R, Marano L, Marrelli D . Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. Cancer Lett. 2016; 372(2):187-91. DOI: 10.1016/j.canlet.2016.01.014. View

Yu Z, Guo W, Ma X, Zhang B, Dong P, Huang L . Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells. Mol Cancer. 2014; 13:203. PMC: 4161895. DOI: 10.1186/1476-4598-13-203. View

Yuan B, Shimada R, Xu K, Han L, Si N, Zhao H . Multiple cytotoxic effects of gamabufotalin against human glioblastoma cell line U-87. Chem Biol Interact. 2019; 314:108849. DOI: 10.1016/j.cbi.2019.108849. View

Li J, Zhao X, Chen L, Guo H, Lv F, Jia K . Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010; 10:529. PMC: 2984425. DOI: 10.1186/1471-2407-10-529. View

Sackmann E . Supported membranes: scientific and practical applications. Science. 1996; 271(5245):43-8. DOI: 10.1126/science.271.5245.43. View

Xiao C, Tong C, Fan J, Wang Z, Xie Q, Long Y . Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation. J Control Release. 2021; 339:259-273. DOI: 10.1016/j.jconrel.2021.09.034. View

Fan J, Liu B, Long Y, Wang Z, Tong C, Wang W . Sequentially-targeted biomimetic nano drug system for triple-negative breast cancer ablation and lung metastasis inhibition. Acta Biomater. 2020; 113:554-569. DOI: 10.1016/j.actbio.2020.06.025. View

Meng H, Wang M, Liu H, Liu X, Situ A, Wu B . Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano. 2015; 9(4):3540-57. PMC: 4415452. DOI: 10.1021/acsnano.5b00510. View

10.

Schroeder A, Heller D, Winslow M, Dahlman J, Pratt G, Langer R . Treating metastatic cancer with nanotechnology. Nat Rev Cancer. 2011; 12(1):39-50. DOI: 10.1038/nrc3180. View

11.

Liu Q, Zhang D, Qian H, Chu Y, Yang Y, Shao J . Superior Antitumor Efficacy of IFN-α2b-Incorporated Photo-Cross-Linked Hydrogels Combined with T Cell Transfer and Low-Dose Irradiation Against Gastric Cancer. Int J Nanomedicine. 2020; 15:3669-3680. PMC: 7261665. DOI: 10.2147/IJN.S249174. View

12.

Nagini S . Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012; 4(7):156-69. PMC: 3406280. DOI: 10.4251/wjgo.v4.i7.156. View

13.

Tammi R, Kultti A, Kosma V, Pirinen R, Auvinen P, Tammi M . Hyaluronan in human tumors: pathobiological and prognostic messages from cell-associated and stromal hyaluronan. Semin Cancer Biol. 2008; 18(4):288-95. DOI: 10.1016/j.semcancer.2008.03.005. View

14.

Tong C, Zhong X, Yang Y, Liu X, Zhong G, Xiao C . PB@PDA@Ag nanosystem for synergistically eradicating MRSA and accelerating diabetic wound healing assisted with laser irradiation. Biomaterials. 2020; 243:119936. DOI: 10.1016/j.biomaterials.2020.119936. View

15.

Cai X, Gao W, Ma M, Wu M, Zhang L, Zheng Y . A Prussian Blue-Based Core-Shell Hollow-Structured Mesoporous Nanoparticle as a Smart Theranostic Agent with Ultrahigh pH-Responsive Longitudinal Relaxivity. Adv Mater. 2015; 27(41):6382-9. DOI: 10.1002/adma.201503381. View

16.

Ajani J, DAmico T, Bentrem D, Chao J, Cooke D, Corvera C . Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022; 20(2):167-192. DOI: 10.6004/jnccn.2022.0008. View

17.

Charalampakis N, Economopoulou P, Kotsantis I, Tolia M, Schizas D, Liakakos T . Medical management of gastric cancer: a 2017 update. Cancer Med. 2017; 7(1):123-133. PMC: 5773977. DOI: 10.1002/cam4.1274. View

18.

Liu B, Wang W, Fan J, Long Y, Xiao F, Daniyal M . RBC membrane camouflaged prussian blue nanoparticles for gamabutolin loading and combined chemo/photothermal therapy of breast cancer. Biomaterials. 2019; 217:119301. DOI: 10.1016/j.biomaterials.2019.119301. View

19.

Chen W, Shi K, Liu J, Yang P, Han R, Pan M . Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer. Bioact Mater. 2022; 23:1-15. PMC: 9650011. DOI: 10.1016/j.bioactmat.2022.10.004. View

20.

Dongre A, Weinberg R . New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2018; 20(2):69-84. DOI: 10.1038/s41580-018-0080-4. View