Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Construction of GPC3-modified Lipopolymer SiRNA Delivery System

Author(s): Dandan Sun, Xiaoyu Li, Yaru Liu, Jishan Quan* and Guangyu Jin*

Volume 30, Issue 19, 2024

Published on: 19 April, 2024

Page: [1507 - 1518] Pages: 12

DOI: 10.2174/0113816128258852231204102044

Price: $65

Abstract

Background: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared.

Methods: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining.

Results: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation.

Conclusion: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

« Previous Next »
[1]
Asafo-Agyei KO, Samant H. Hepatocellular carcinoma. Treasure Island, FL: StatPearls 2022.
[2]
Sahin ID, Christodoulou MS, Guzelcan EA, et al. A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition. Sci Rep 2020; 10(1): 11814.
[http://dx.doi.org/10.1038/s41598-020-68775-9] [PMID: 32678233]
[3]
Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature 2004; 427(6977): 779-81.
[http://dx.doi.org/10.1038/427779a] [PMID: 14985734]
[4]
Kaiser J. Clinical research. Gene therapists celebrate a decade of progress. Science 2011; 334(6052): 29-30.
[http://dx.doi.org/10.1126/science.334.6052.29] [PMID: 21980087]
[5]
Zhao Y, Zhao T, Du Y, et al. Interaction kinetics of peptide lipids- mediated gene delivery. J Nanobiotechnol 2020; 18(1): 144.
[http://dx.doi.org/10.1186/s12951-020-00707-1] [PMID: 33069258]
[6]
Lundstrom K. Viral vectors in gene therapy: Where do we stand in 2023? Viruses 2023; 15(3): 698.
[http://dx.doi.org/10.3390/v15030698] [PMID: 36992407]
[7]
Sun D, Jin G, Jin Z, et al. Construction of a visualized liver-targeting siRNA delivery system. J Drug Deliv Sci Technol 2023; 85: 104566.
[http://dx.doi.org/10.1016/j.jddst.2023.104566]
[8]
Lu Y, Li J, Su N, Lu D. The mechanism for siRNA transmembrane assisted by PMAL. Molecules 2018; 23(7): 1586.
[http://dx.doi.org/10.3390/molecules23071586] [PMID: 29966273]
[9]
Zu H, Gao D. Non-viral vectors in gene therapy: Recent development, challenges, and prospects. AAPS J 2021; 23(4): 78.
[http://dx.doi.org/10.1208/s12248-021-00608-7] [PMID: 34076797]
[10]
Mirzaei S, Paskeh MDA, Entezari M, et al. siRNA and targeted delivery systems in breast cancer therapy. Clin Transl Oncol 2022; 25(5): 1167-88.
[http://dx.doi.org/10.1007/s12094-022-03043-y] [PMID: 36562927]
[11]
Li D, Gao C, Kuang M, et al. Nanoparticles as drug delivery systems of RNAi in cancer therapy. Molecules 2021; 26(8): 2380.
[http://dx.doi.org/10.3390/molecules26082380] [PMID: 33921892]
[12]
Duan Y, Guan X, Ge J, et al. Cationic nano-copolymers mediated IKKbeta targeting siRNA inhibit the proliferation of human Tenon’s capsule fibroblasts in vitro. Mol Vis 2008; 14: 2616-28.
[PMID: 19137061]
[13]
Sánchez-Moreno P, de Vicente J, Nardecchia S, Marchal J, Boulaiz H. Thermo-sensitive nanomaterials: Recent advance in synthesis and biomedical applications. Nanomaterials 2018; 8(11): 935.
[http://dx.doi.org/10.3390/nano8110935] [PMID: 30428608]
[14]
Mellott AJ, Shinogle HE, Moore DS, Detamore MS. Fluorescent Photo-conversion: A second chance to label unique cells. Cell Mol Bioeng 2015; 8(1): 187-96.
[http://dx.doi.org/10.1007/s12195-014-0365-4] [PMID: 25914756]
[15]
Chen Z, Krishnamachary B, Bhujwalla Z. Degradable dextran nanopolymer as a carrier for Choline Kinase (ChoK) siRNA cancer therapy. Nanomaterials 2016; 6(2): 34.
[http://dx.doi.org/10.3390/nano6020034] [PMID: 28344291]
[16]
Sun W, Wang Y, Cai M, et al. Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy. Biomater Sci 2017; 5(12): 2468-79.
[http://dx.doi.org/10.1039/C7BM00866J] [PMID: 29106433]
[17]
Zhang L, Chan JM, Gu FX, et al. Self-assembled lipid-polymer hybrid nanoparticles: A robust drug delivery platform. ACS Nano 2008; 2(8): 1696-702.
[http://dx.doi.org/10.1021/nn800275r] [PMID: 19206374]
[18]
García L, Buñuales M, Düzgüneş N, Tros de Ilarduya C. Serum-resistant lipopolyplexes for gene delivery to liver tumour cells. Eur J Pharm Biopharm 2007; 67(1): 58-66.
[http://dx.doi.org/10.1016/j.ejpb.2007.01.005] [PMID: 17321729]
[19]
Wang J, Ye X, Ni H, Zhang J, Ju S, Ding W. Transfection efficiency evaluation and endocytosis exploration of different polymer condensed agents. DNA Cell Biol 2019; 38(10): 1048-55.
[http://dx.doi.org/10.1089/dna.2018.4464] [PMID: 31433200]
[20]
Ewe A, Panchal O, Pinnapireddy SR, et al. Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo. Nanomedicine 2017; 13(1): 209-18.
[http://dx.doi.org/10.1016/j.nano.2016.08.005] [PMID: 27553077]
[21]
Lungwitz U, Breunig M, Blunk T, Göpferich A. Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm 2005; 60(2): 247-66.
[http://dx.doi.org/10.1016/j.ejpb.2004.11.011] [PMID: 15939236]
[22]
Shih TC, Wang L, Wang HC, Wan YJY. Glypican-3: A molecular marker for the detection and treatment of hepatocellular carcinoma. Liver Res 2020; 4(4): 168-72.
[http://dx.doi.org/10.1016/j.livres.2020.11.003] [PMID: 33384879]
[23]
An S, Zhang D, Zhang Y, et al. GPC3-targeted immunoPET imaging of hepatocellular carcinomas. Eur J Nucl Med Mol Imaging 2022; 49(8): 2682-92.
[http://dx.doi.org/10.1007/s00259-022-05723-x] [PMID: 35147737]
[24]
Montalbano M, Georgiadis J, Masterson AL, et al. Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma. Oncol Rep 2017; 37(3): 1291-300.
[http://dx.doi.org/10.3892/or.2017.5387] [PMID: 28098909]
[25]
Lai JP, Oseini AM, Moser CD, et al. The oncogenic effect of sulfatase 2 in human hepatocellular carcinoma is mediated in part by glypican 3-dependent Wnt activation. Hepatology 2010; 52(5): 1680-9.
[http://dx.doi.org/10.1002/hep.23848] [PMID: 20725905]
[26]
Liu S, Li Y, Chen W, et al. Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 2012; 419(4): 656-61.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.069] [PMID: 22382024]
[27]
Xing M, Wang X, Kirken R, He L, Zhang JY. Immunodiagnostic biomarkers for Hepatocellular Carcinoma (HCC): The first step in detection and treatment. Int J Mol Sci 2021; 22(11): 6139.
[http://dx.doi.org/10.3390/ijms22116139] [PMID: 34200243]
[28]
Zheng X, Liu X, Lei Y, Wang G, Liu M. Glypican-3: A novel and promising target for the treatment of hepatocellular carcinoma. Front Oncol 2022; 12: 824208.
[http://dx.doi.org/10.3389/fonc.2022.824208] [PMID: 35251989]
[29]
Sun J, Zhou Y, Jin G, Jin Y, Quan J. Preparation and preliminary evaluation of dual-functional nanoparticles for MRI and siRNA delivery. Iran J Pharm Res 2021; 20(4): 265-77.
[PMID: 35194445]
[30]
Yoo MK, Park IK, Lim HT, et al. Folate-PEG-superparamagnetic iron oxide nanoparticles for lung cancer imaging. Acta Biomater 2012; 8(8): 3005-13.
[http://dx.doi.org/10.1016/j.actbio.2012.04.029] [PMID: 22543005]
[31]
Ghaffari M, Dehghan G, Abedi-Gaballu F, et al. Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting. Eur J Pharm Sci 2018; 122: 311-30.
[http://dx.doi.org/10.1016/j.ejps.2018.07.020] [PMID: 30003954]
[32]
Bhatt H, Kiran Rompicharla SV, Ghosh B, Torchilin V, Biswas S. Transferrin/α-tocopherol modified poly(amidoamine) dendrimers for improved tumor targeting and anticancer activity of paclitaxel. Nanomedicine 2019; 14(24): 3159-76.
[http://dx.doi.org/10.2217/nnm-2019-0128] [PMID: 31855118]
[33]
Chouly C, Pouliquen D, Lucet I, Jeune JJ, Jallet P. Development of superparamagnetic nanoparticles for MRI: Effect of particle size, charge and surface nature on biodistribution. J Microencapsul 1996; 13(3): 245-55.
[http://dx.doi.org/10.3109/02652049609026013] [PMID: 8860681]
[34]
Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2003; 2(3): 214-21.
[http://dx.doi.org/10.1038/nrd1033] [PMID: 12612647]
[35]
Yamazaki Y, Nango M, Matsuura M, Hasegawa Y, Hasegawa M, Oku N. Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine. Gene Ther 2000; 7(13): 1148-55.
[http://dx.doi.org/10.1038/sj.gt.3301217] [PMID: 10918482]
[36]
Nieto González N, Obinu A, Rassu G, Giunchedi P, Gavini E. Polymeric and lipid nanoparticles: Which applications in pediatrics? Pharmaceutics 2021; 13(5): 670.
[http://dx.doi.org/10.3390/pharmaceutics13050670] [PMID: 34066953]
[37]
Liu X, Gao F, Jiang L, et al. 32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma. J Transl Med 2020; 18(1): 295.
[http://dx.doi.org/10.1186/s12967-020-02462-1] [PMID: 32746924]
[38]
Kostevšek N, Cheung CCL, Serša I, et al. Magneto-liposomes as MRI contrast agents: A systematic study of different liposomal formulations. Nanomaterials 2020; 10(5): 889.
[http://dx.doi.org/10.3390/nano10050889] [PMID: 32384645]
[39]
Wang B, Wu W, Lu H, Wang Z, Xin H. Enhanced anti-tumor of pep-1 modified superparamagnetic iron oxide/ptx loaded polymer nanoparticles. Front Pharmacol 2019; 9: 1556.
[http://dx.doi.org/10.3389/fphar.2018.01556] [PMID: 30723412]
[40]
Amin K, Dannenfelser RM. In vitro hemolysis: Guidance for the pharmaceutical scientist. J Pharm Sci 2006; 95(6): 1173-6.
[http://dx.doi.org/10.1002/jps.20627] [PMID: 16639718]
[41]
Zhang H. Preparation and Preliminary Evaluation of Glycosaminoglycans Modified Superparamagnetic Iron Oxide Nanoparticles as MRI Negative Contrast Agents. Shandong China: Shandong University 2020.
[42]
Singh N, Sahoo SK, Kumar R. Hemolysis tendency of anticancer nanoparticles changes with type of blood group antigen: An insight into blood nanoparticle interactions. Mater Sci Eng C 2020; 109: 110645.
[http://dx.doi.org/10.1016/j.msec.2020.110645] [PMID: 32228982]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy