|
|
|
| The Preparation and Biological Study of Amphiphilic Glycopolypeptides as Liver-Targeted Theranostic Nanoparticles |
| Lai Shengsheng1#, Liu Qiancheng1, Jin Haoyu1, Liu Wenping1, Zhu Huier2* |
1(School of Medical Instruments, Guangdong Food and Drug Vocational College, Guangzhou 510520, China)
2(Department of Emergency, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China) |
|
|
|
|
Abstract In this work, amphiphilic glycopolypeptides were synthesized by a sequential ring opening polymerization of ε-carbobenzyloxy-L-lysine N-carboxyanhydride and glutamic acid based N-carboxyanhydride monomer. Galactosyl sugar units as targeting ligands were conjugated to the polypeptides block via an efficient click reaction. The chemical structures of the obtained glycopolypeptides were characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis. Glycopolypeptides base nanoparticles were prepared by dialysis method in aqueous solution, followed by characterized with fluorometry, transmission electron microscopy and dynamic light scattering. The biological activity was demonstrated by selective lectin binding experiments. The cytotoxicity of the glycopolypeptides was investigated by MTT test. Furthermore, liver targeted theranostic nanoparticles were prepared by using glycopolypeptides acted as nano-cargo to load near infrared dyes IR780. The cellular uptake, photothermal therapy effect and in vivo tumor imaging were investigated by using fluorescence imaging, quantitative flow cytometry and in vivo imaging system. Results indicated that the amphiphilic glycopolypeptides were obtained via the combination of ring open polymerization and “click” reaction. Own to their amphiphilic property, glycopolypeptides self-assembled into spherical nanoparticles with about 85 nm in diameter in an aqueous medium once the concentration was over 0.015 μg/mL. MTT results revealed that the glycopolypeptides nanoparticles was nontoxic to HepG2 cells and HUVECs even the concentration was up to 500 μg/mL. Fluorescence microscope revealed the specific recognition between glycopolypeptides and ricin agglutinin. According to the flow cytometry results, glycopolypeptides nanoparticles could deliver IR780 into the HepG2 cells effectively. Photothermal therapy study revealed that higher doses of IR-780 killed more tumor cells after laser irradiation at 808 nm. In vivo NIRF imaging shown that the theranostics nanoparticles were mainly accumulated in the tumor mass, even after 24 h, strong flourescence signals were still detected from the tumor mass. The glycopolypeptides were demonstrated promising tumor targeting theranostic nanocarriers.
|
|
Received: 08 May 2018
|
|
|
|
|
|
[1] 张志伟.我国开展肝癌多学科团队诊疗模式的困难与对策 [J]. 肝胆外科杂志, 2014, 22(4): 243-244.
[2] Yu MK, Park J, Jon S. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy [J]. Theranostics, 2012, 2(1): 3-44.
[3] Wang Zhao, Sheng Ruilong, Luo Ting, et al. Synthesis and self-assembly of diblock glycopolypeptide analogues PMAgala-b-PBLG as multifunctional biomaterials for protein recognition, drug delivery and hepatoma cell targeting [J]. Polymer Chemistry, 2017, 8(2): 472-484.
[4] Wang Xiaoyan, Sun Huanli, Meng Fenghua, et al. Galactose-decorated reduction-sensitive degradable chimaeric polymersomes as a multifunctional nanocarrier to efficiently chaperone apoptotic proteins into hepatoma cells [J]. Biomacromolecules, 2013, 14(8): 2873-2882.
[5] Yi Xiaomin, Wang Fuli, Qin Weijun, et al. Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field [J]. International Journal of Nanomedicine, 2014, 9(1), 1347-1365.
[6] Yang Huikang, Qi Meng, Mo Lei, et al. Reduction-sensitive amphiphilic dextran derivatives as theranostic nanocarriers for chemotherapy and MR imaging [J]. RSC Advances, 2016, 6(115): 114519-114531.
[7] 武莉, 陈静, 刘天军. 磷脂酰聚乙二醇单甲醚的合成及其自组装纳米胶束的研究[J].中国生物医学工程学报, 2012, 31(6): 910-917.
[8] Xiao Chunsheng, Zhao Changwen, He Pan, et al. Facile synthesis of glycopolypeptides by combination of ring-opening polymerization of an alkyne-substituted N-carboxyanhydride and click “glycosylation”[J]. Macromolecular Rapid Communications, 2010, 31(11): 991-997.
[9] Kim EH, Misek DE. Glycoproteomics-based identification of cancer biomarkers. international journal of proteomics [J]. International Journal of Proteomics, 2011, 2011: 601937.
[10] Rudd PM, Elliott T, Cresswell P, et al. Glycosylation and the immune system [J]. Science, 2001, 291(5512): 2370-2376.
[11] Deming TJ. Synthesis of side-chain modified polypeptides [J]. Chemical Reviews, 2016, 116(3): 786-808.
[12] Bonduelle C, Huang Jin, Ibarboure E, et al. Synthesis and self-assembly of "tree-like" amphiphilic glycopolypeptides [J]. Chemical Communications, 2012, 48(67): 8353-8355.
[13] Bonduelle C, Lecommandoux S. Glycopolypeptides as biomimetic analogues of natural glycoproteins [J]. Biomacromolecules, 2013, 14 (9): 2973-2983.
[14] Upadhyay KK, Meins JFL, Misra A, et al. Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(γ-benzyl glutamate) copolymers [J]. Biomacromolecules, 2009, 10(10): 2802-2808.
[15] Pati D, Shaikh AY, Das S, et al. Controlled synthesis of o-glycopolypeptide polymers and their molecular recognition by lectins [J]. Biomacromolecules, 2012, 13(5): 1287-1295.
[16] Kramer JR, Deming TJ. Preparation of multifunctional and multireactive polypeptides via methionine alkylation [J]. Biomacromolecules, 2012, 13(6): 1719-1723.
[17] Mildner R, Menzel H. Hydrophobic spacers enhance the helicity and lectin binding of synthetic, pH-responsive glycopolypeptides [J]. Biomacromolecules, 2014, 15(12): 4528-4533.
[18] Pati D, Shaikh AY, Hotha S, et al. Synthesis of glycopolypeptides by the ring opening polymerization of O-glycosylated-α-amino acid N-carboxyanhydride (NCA) [J]. Polymer Chemistry, 2011, 2(4): 805-811.
[19] Shaikh AY, Das S, Pati D, et al. Cationic charged helical glycopolypeptide using ring opening polymerization of 6-Deoxy-6-azido-glyco-N-carboxyanhydride [J]. Biomacromolecules, 2014, 15(10): 3679-3686.
[20] Gauche C, Lecommandoux S. Versatile design of amphiphilic glycopolypeptides nanoparticles for lectin recognition [J]. Polymer, 2016, 107: 474-484.
[21] Yang Huikang, Bao Junfang, Mo Lei, et al. Bioreducible amphiphilic block copolymers based on PCL and glycopolypeptide as multifunctional theranostic nanocarriers for drug delivery and MR imaging [J]. RSC Advances, 2017, 7(34): 21093-21106. |
| [1] |
Li Baoming, Hu Jiarui, Xu Haijun, Wang Cong, Jiang Yanni, Zhang Zhihong, Xu Jun. Deep Cascaded Network for Automated Detection of Cancer MetastasisRegion from Whole Slide Image of Breast Lymph Node[J]. Chinese Journal of Biomedical Engineering, 2020, 39(3): 257-264. |
| [2] |
Xie Sudan, Fan Ming, Xu Maosheng, Wang Shiwei, Li Lihua. Prediction of Histological Grade in Invasive Breast Cancer Based on T2-Weighted MRI[J]. Chinese Journal of Biomedical Engineering, 2020, 39(3): 280-287. |
|
|
|
|
