Fluorescent carbon dots as an efficient siRNA nanocarrier for its interference therapy in gastric cancer cells

Journal of Nanobiotechnology

Daxiang Cui¹  Hualin Fu¹  Huiyang Liu¹  Guangxia Shen¹  Chunlei Zhang¹  Qing Wang¹ 

[1] Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China

关键词: Nanocarriers;    Gastric cancer;    siRNA interference therapy;    Carbon dots;   

Others  :  1139181
DOI  :  10.1186/s12951-014-0058-0

 received in 2014-10-28, accepted in 2014-12-05,  发布年份 2014

【 摘 要 】

Background

Fluorescent carbon dots (Cdots) have attracted increasing attention due to their potential applications in sensing, catalysis, and biomedicine. Currently, intensive research has been concentrated on the synthesis and imaging-guided therapy of these benign photoluminescent materials. Meanwhile, Cdots have been explored as nonviral vector for nucleic acid or drug delivery by chemical modification on purpose.

Results

We have developed a microwave assisted one-step synthesis of Cdots with citric acid as carbon source and tryptophan (Trp) as both nitrogen source and passivation agent. The Cdots with uniform size show superior water solubility, excellent biocompatibility, and high quantum yield. Afterwards, the PEI (polyethylenimine)-adsorbed Cdots nanoparticles (Cdots@PEI) were applied to deliver Survivin siRNA into human gastric cancer cell line MGC-803. The results have confirmed the nanocarrier exhibited excellent biocompatibility and a significant increase in cellular delivery of siRNA, inducing efficient knockdown for Survivin protein to 6.1%. In addition, PEI@Cdots complexes mediated Survivin silencing, the arrested cell cycle progression in G₁ phase as well as cell apoptosis was observed.

Conclusion

The Cdots-based and PEI-adsorbed complexes both as imaging agents and siRNA nanocarriers have been developed for Survivin siRNA delivery. And the results indicate that Cdots-based nanocarriers could be utilized in a broad range of siRNA delivery systems for cancer therapy.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Peer D, Karp JM, Hong S, FaroKhzad OC, Margalit R, Langer R: Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007, 2:751-760.
• [2]Wang M, Thanou M: Targeting nanoparticles to cancer. Pharmacol Res 2010, 62:90-99.
• [3]Zhang C, Zhou Z, Qian Q, Gao G, Li C, Feng L, Wang Q, Cui D: Glutathione-capped fluorescent gold nanoclusters for dual-modal fluorescence/X-ray computed tomography imaging. J Mater Chem B 2013, 1:5045-5053.
• [4]Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S: Quantum dots for live cells, in vivo imaging, and diagnostics. Science 2005, 307:538-544.
• [5]Disney MD, Zheng J, Swager TM, Seeberger PH: Detection of bacteria with carbohydrate-functionalized fluorescent polymers. J Am Chem Soc 2004, 126:13343-13346.
• [6]Baker SN, Baker GA: Luminescent carbon nanodots: emergent Nanolights. Angew Chem Int Ed 2010, 49:6726-6744.
• [7]Li H, Kang Z, Liu Y, Lee S-T: Carbon nanodots: synthesis, properties and applications. J Mater Chem 2012, 22:24230-24253.
• [8]Derfus AM, Chan WCW, Bhatia SN: Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 2003, 4:11-18.
• [9]Song Y, Shi W, Chen W, Li X, Ma H: Fluorescent carbon nanodots conjugated with folic acid for distinguishing folate-receptor-positive cancer cells from normal cells. J Mater Chem 2012, 22:12568-12573.
• [10]Ruan S, Qian J, Shen S, Zhu J, Jiang X, He Q, Gao H: A simple one-step method to prepare fluorescent carbon dots and their potential application in non-invasive glioma imaging. Nanoscale 2014, 6:10040-10047.
• [11]Liu J-M, Lin L-p, Wang X-X, Lin S-Q, Cai W-L, Zhang L-H, Zheng Z-Y: Highly selective and sensitive detection of Cu2+with lysine enhancing bovine serum albumin modified-carbon dots fluorescent probe.Analyst 2012, 137:2637–2642.
• [12]Wang Q, Liu X, Zhang L, Lv Y: Microwave-assisted synthesis of carbon nanodots through an eggshell membrane and their fluorescent application. Analyst 2012, 137:5392-5397.
• [13]Du F, Zhang M, Li X, Li J, Jiang X, Li Z, Hua Y, Shao G, Jin J, Shao Q, Zhou M, Gong A: Economical and green synthesis of bagasse-derived fluorescent carbon dots for biomedical applications.Nanotechnology 2014, 25(31):315702–315712.
• [14]Peng J, Gao W, Gupta BK, Liu Z, Romero-Aburto R, Ge L, Song L, Alemany L, Zhan X, Gao G, Vithayathil S, Kaipparettu B, Marti A, Hayashi T, Zhu J, Ajayan P: Graphene quantum dots derived from carbon fibers. Nano Lett 2012, 12(2):844-849.
• [15]Lu J, Yeo PSE, Gan CK, Wu P, Loh KP: Transforming C60molecules into graphene quantum dots.Nat Nanotechnol 2011, 6:247–252.
• [16]Wu ZL, Zhang P, Gao MX, Liu CF, Wang W, Leng F, Huang CZ: One-pot hydrothermal synthesis of highly luminescent nitrogen-doped amphoteric carbon dots for bioimaging from Bombyx mori silk - natural proteins. J Mater Chem B 2013, 1:2868-2873.
• [17]Sun Y-P, Wang X, Lu F, Cao L, Meziani MJ, Luo PG, Gu L, Veca L: Doped carbon nanoparticles as a new platform for highly photoluminescent dots. J Phys Chem C 2008, 112(47):18295-18298.
• [18]Liu H, Wang Q, Shen G, Zhang C, Li C, Ji W, Wang C, Cui D: A multifunctional ribonuclease A-conjugated carbon dot cluster nanosystem for synchronous cancer imaging and therapy. Nanoscale Res Lett 2014, 9:397. BioMed Central Full Text
• [19]Huang P, Lin J, Wang X, Wang Z, Zhang C, He M, Wang K, Chen F, Li Z, Shen G, Cui D, Chen X: Light-triggered theranostics based on photosensitizer-conjugated carbon dots for simultaneous enhanced-fluorescence imaging and photodynamic therapy. Adv Mater 2012, 24(37):5104-5110.
• [20]Hannon GJ: RNA interference. Nature 2002, 418:244-251.
• [21]Fellmann C, Lowe SW: Stable RNA interference rules for silencing. Nat Cell Biol 2014, 16:10-18.
• [22]Maillard PV, Ciaudo C, Marchais A, Li Y, Jay F, Ding SW, Voinnet O: Antiviral RNA interference in mammalian cells. Science 2013, 342:235-238.
• [23]Wang L, Wang X, Bhirde A, Cao J, Zeng Y, Huang X, Sun Y, Liu G, Chen X: Carbon-Dot-based Two-photon visible nanocarriers for safe and highly efficient delivery of siRNA and DNA. Adv Healthcare Mater 2014, 3:1203-1209.
• [24]Liu C, Zhang P, Zhai X, Tian F, Li W, Yang J, Liu Y, Wang H, Wang W, Liu W: Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence. Biomaterials 2012, 33:3604-3613.
• [25]Qi L, Shao W, Shi D: JAM-2 siRNA intracellular delivery and real-time imaging by proton-sponge coated quantum dots. J Mater Chem B 2013, 1:654-660.
• [26]Yang D, Welm A, Bishop JM: Cell division and cell survival in the absence of survivin. Proc Natl Acad Sci 2004, 101:15100-15105.
• [27]Suzuki A, Hayashida M, Ito T, Kawano H, Nakano T, Miura M, Akahane K, Shiraki K: Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/Cyclin E complex activation. Oncogene 2000, 19:3225-3234.
• [28]Lu CD, Altieri DC, Tanigawa N: Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 1998, 58:1808-1812.
• [29]Parhamifar L, Larsen AK, Hunter AC, Andresen TL, Moghimi SM: Polycation cytotoxicity: a delicate matter for nucleic acid therapy-focus on polyethylenimine. Soft Matter 2010, 6:4001-4009.
• [30]Montazeri Aliabadi H, Landry B, Mahdipoor P, Uludağ H: Induction of apoptosis by survivin silencing through siRNA delivery in a human breast cancer cell line. Mol Pharmaceutics 2011, 8:1821-1830.