Synthesis of novel galactose functionalized gold nanoparticles and its radiosensitizing mechanism

Journal of Nanobiotechnology

Jian-qing Wu³  Yuan Wan²  Quan-an Zhang¹  Jin-long Tong¹  Han-Feng Xu¹  Li-xue Wang¹  Qin Zheng¹  Chuan-dong Zhu¹ 

[1] Department of Oncology, The Second Hospital Affiliated of Southeast University, Nanjing, 210003, Jiangsu, People’s Republic of China;PerMed Biomedical Co. Ltd., 575 Bibo Road, Shanghai, 201203, People’s Republic of China;Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210019, Jiangsu, People’s Republic of China

关键词: Hepatocellular carcinoma;    Radiosensitization;    γ-H2AX;    Polyethylene glycol;    Galactose;    Gold nanoparticles;   

Others  :  1231735
DOI  :  10.1186/s12951-015-0129-x

 received in 2015-04-28, accepted in 2015-09-25,  发布年份 2015

【 摘 要 】

Background

Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability.

Results

This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing.

Conclusion

GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.

【 授权许可】

   
2015 Zhu et al.

【 图 表 】

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【 参考文献 】

• [1]Zeng ZC, Jiang GL. DNA-PKcs subunits in radiosensitization by hyperthermia on hepatocellular carcinoma hepG2 cell line. World J Gastroenterol. 2002; 8(5):797-803.
• [2]Tai A, Erickson B, Khater KA, Li XA. Estimate of radiobiologic parameters from clinical data for biologically based treatment planning for liver irradiation. Int J Radiat Oncol Biol Phys. 2008; 70(3):900-907.
• [3]Ursino S, Greco C, Cartei F, Colosimo C, Stefanelli A, Cacopardo B et al.. Radiotherapy and hepatocellular carcinoma: update and review of the literature. Eur Rev Med Pharmacol Sci. 2012; 16(11):1599-1604.
• [4]Feng M, Ben-Josef E. Radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol. 2011; 21(4):271-277.
• [5]Gil-Alzugaray B, Chopitea A, Iñarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J et al.. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. 2013; 57(3):1078-1087.
• [6]Wiersma RD, Mao W, Xing L. Combined kV and MV imaging for real-time tracking of implanted fiducial markers. Med Phys. 2008; 35(4):1191-1198.
• [7]Nairi CK, Parida DK, Nomura T. Radioprotectors in Radiotherapy. J Radiat Res. 2001; 42(1):21-37.
• [8]Lee IJ, Seong J. Radiosensitizers in hepatocellular carcinoma. Semin Radiat Oncol. 2011; 21(4):303-311.
• [9]Wardman P. Chemical radiosensitizers for use in radiotherapy. Clin Oncol. 2007; 19(6):397-417.
• [10]Zhua AX, Willetta CG. Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer. Semin Radiat Oncol. 2003; 13(4):454-468.
• [11]Urick ME, Chung EJ, Shield WP, Gerber N, White A, Sowers A et al.. Enhancement of 5-fluorouracil induced in vitro and in vivo radiosensitization with MEK inhibition. Clin Cancer Res. 2011; 17(15):5038-5047.
• [12]Toulany M, Mihatsch J, Holler M, Chaachouay H, Rodemann HP. Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is stimulated by ATM inhibition. Radiother Oncol. 2014; 111(2):228-236.
• [13]Daniel MC, Astruc D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications to-ward biology, catalysis and nanotechnology. Chem Rev. 2004; 104(1):293-346.
• [14]Zheng Q, Yang H, Wei J, Tong JL, Shu YQ. The role and mechanisms of nanoparticles to enhance radiosensitivity in hepatocellular cell. Biomed Pharmacother. 2013; 67(7):569-575.
• [15]Jain S, Coulter JA, Hounsell AR, Butterworth KT, McMahon SJ, Hyland WB et al.. Cell-specific radiosensitization by gold nanoparticles at megavoltage radiation energies. Int J Radiat Oncol Biol Phys. 2011; 79(2):531-539.
• [16]Chattopadhyay N, Cai Z, Kwon YL, Lechtman E, Pignol JP, Reilly RM. Molecularly targeted gold nanoparticles enhance the radiation response of breast cancer cells and tumor xenografts to X-radiation. Breast Cancer Res Treat. 2013; 137(1):81-91.
• [17]Chithrani DB, Jelveh S, Jalali F, van Prooijen M, Allen C, Bristow RG et al.. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat Res. 2010; 173(6):719-728.
• [18]Ma H, Liu J, Ali MM, Mahmood MA, Labanieh L, Lu M et al.. Nucleic acid aptamers in cancer research, diagnosis and therapy. Chem Soc Rev. 2015; 44(5):1240-1256.
• [19]Yik JH, Saxena A, Weigel JA, Weigel PH. Palmitoylation-defective asialoglycoprotein receptors are normal in their cellular distribution and ability to bind ligand, but are defective in ligand uptake and degradation. Biochem Biophys Res Commun. 2002; 297(4):980-986.
• [20]Park E, Manzella SM, Baenziger JU. Rapid clearance of sialylated glycoproteins by the asialoglycoprotein receptor. J Biol Chem. 2003; 278(7):4597-4602.
• [21]Jeong YI, Seo SJ, Park IK, Lee HC, Kang IC, Akaike T et al.. Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(gamma-benzyl-l-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety. Int J Pharm. 2005; 296(1–2):151-161.
• [22]Liu ZX, Wu YC, Guo ZR, Liu Y, Shen Y, Zhou P et al.. Effects of internalized gold nanoparticles with respect to cytotoxicity and invasion activity in lung cancer cells. PLoS One. 2014; 9(6):e99175.
• [23]Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007; 2(12):751-760.
• [24]Jain S, Hirst DG, O’Sullivan JM. Gold nanoparticles as novel agents for cancer therapy. Br J Radiol. 1010; 2012(85):101-113.
• [25]Choi Y, Kang T, Lee LP. Plasmon resonance energy transfer (PRET)-based molecular imaging of cytochrome C in living cells. Nano Lett. 2009; 9(1):80-90.
• [26]Yeh YC, Creran B, Rotello VM. Gold nanoparticles: preparation, properties, and applications in bionanotechnology. Nanoscale. 2012; 4(6):1871-1880.
• [27]Kang B, Afifi MM, Austin LA, El-Sayed MA. Exploiting the nanoparticle plasmon effect: observing drug delivery dynamics in single cells via Raman/fluorescence imaging spectroscopy. ACS Nano. 2013; 7(8):7420-7427.
• [28]Rahman WN, Bishara N, Ackerly T, He CF, Jackson P, Wong C et al.. Enhancement of radiation effects by gold nanoparticles for superficial radiation therapy. Nanomedicine. 2009; 5(2):136-142.
• [29]Liu CJ, Wang CH, Chien CC, Yang TY, Chen ST, Leng WH et al.. Enhanced X-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a Flew synthesis method of polyethylene glycol modification. Nanotechnology. 2008; 19(99):95-104.
• [30]Kong T, Zeng J, Wang XP, Yang X, Yang J, McQuarrie S et al.. Enhancement of radiation eytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles. Small. 2008; 4(9):1537-1543.
• [31]Hainfeld JF, Slatkin DN, Smilowitz HM. The use of gold nanoparticles to enhance radiotherapy in mice. Phys Med Biol. 2004; 49(18):309-315.
• [32]Brun E, Sanche L, Sicard-Roselli C. Parameters governing gold nanoparticle X-ray radiosensitization of DNA in solution. Colloids Surf B: Biointerfaces. 2009; 72(1):128-134.
• [33]Leung MK, Chow JC, Chithrani BD, Lee MJ, Oms B, Jaffray DA. Irradiation of gold nanoparticles by X-rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production. Med Phys. 2011; 38(2):624-631.
• [34]Mesbahi A, Jamali F, Garehaghaji N. Effect of photon beam energy, gold nanoparticle size and concentration on the dose enhancement in radiation therapy. Bioimpacts. 2013; 3(1):29-35.
• [35]Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev. 2011; 40(3):1647-1671.
• [36]Geng F, Song K, Xing JZ, Yuan C, Yan S, Yang Q et al.. Thio-glucose bound gold nanoparticles enhance radiocytotoxic targeting of ovarian cancer. Nanotechnology. 2011; 22(28):285101.
• [37]Zhang X, Xing JZ, Chen J, Ko L, Amanie J, Gulavita S et al.. Enhanced radiation sensitivity in prostate cancer by goldnanoparticles. Clin Invest Med. 2008; 31(3):e160-e167.
• [38]Turner J, Koumenis C, Kute TE, Planalp RP, Brechbiel MW, Beardsley D et al.. Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation. Blood. 2005; 106(9):3191-3199.
• [39]Zoler F, Jagetia G, Streffer C. G2-block after irradiation of cells with different p53 status. Strahlenther Onkol. 2014; 190(11):1075-1079.
• [40]Butterworth KT, McMahon SJ, Currell FJ, Prise KM. Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale. 2012; 4(16):4830-4838.