Abstract
Graphene quantum dots capped in hollow mesoporous silica nanoparticles (GQDs@hMSN) exhibited great potential in medical applications due to its good optical properties and high drug loading capacity. Compared with antibodies, peptide has a better affinity with target proteins. Herein, we demonstrated efficient targeting of triple-negative breast cancer with GQDs@hMSN, which was conjugated to a peptide ligand, F3 against nucleolin, to form GQDs@hMSN-F3. The core/shell GQDs@hMSN and GQDs@hMSN-F3 had diameters of 100 nm and 130 nm, respectively, based on transmission electron microscope (TEM) and dynamic laser scattering (DLS) measurement. Doxorubicin (DOX) was loaded onto GQDs@hMSN with a relatively high loading capacity. Systematic in vitro and in vivo studies were performed to investigate the targeting specificity and tissue distribution of GQDs@hMSN conjugates. Fluorescence microscopy examination and flow cytometry confirmed the targeting specificity of F3-attached GQDs@hMSN conjugates against cell nucleolin. A more potent uptake of GQDs@hMSN-F3 in MDA-MB-231 nodules was witnessed when compared with that of non-targeted GQDs@hMSN. Based on the findings from cellular targeting and in vivo fluorescence imaging, F3-attached GQDs@hMSN conjugates had the potential to serve as an image-guidable, tumor-selective cargo delivery nanoplatform.
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References
Chen D, Yang D, Dougherty CA, Lu W, Wu H, He X, Cai T, Van Dort ME, Ross BD, Hong H (2017) In vivo targeting and positron emission tomography imaging of tumor with intrinsically radioactive metal-organic frameworks nanomaterials. ACS Nano 11(4):4315–4327
Cornelissen B, Waller A, Target C, Kersemans V, Smart S, Vallis KA (2012) 111In-BnDTPA-F3: an auger electron-emitting radiotherapeutic agent that targets nucleolin. EJNMMI Res 2:9
Dong J, Yao X, Sun S, Zhong Y, Qian C, Yang D (2019) In vivo targeting of breast cancer with a vasculature-specific GQDs/hMSN nanoplatform. RSC Adv 9:11576–11584
Fomo G, Achadu OJ, Nyokong T (2018) One-pot synthesis of graphene quantum dots-phthalocyanines supramolecular hybrid and the investigation of their photophysical properties. J Mater Sci 53(1):538–548
Flak D, Przysiecka Ł, Nowaczyk G, Scheibe B, Kościński M, Jesionowski T, Jurga S (2018) GQDs-MSNs nanocomposite nanoparticles for simultaneous intracellular drug delivery and fluorescent imaging. J Nanopart Res 20(11):306
Ge J, Lan M, Zhou B, Liu W, Guo L, Wang H, Jia Q, Niu G, Huang X, Zhou H, Meng X, Wang P, Lee CS, Zhang W, Han X (2014) A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation. Nat Commun 5:4596
Ham SH, Min KA, Shin MC (2017) Molecular tumor targeting of gelonin by fusion with F3 peptide. Acta Pharmacol Sin 38(6):897–906
Han LB, Zhou Y, He T, Song GS, Wu F, Jiang FR, Hu JQ (2013) One-pot morphology-controlled synthesis of various shaped mesoporous silica nanoparticles. J Mater Sci 48(17):5718–5726
Hu Q, Gu G, Liu Z, Jiang M, Kang T, Miao D, Tu Y, Pang Z, Song Q, Yao L, Xia H, Chen H, Jiang X, Gao X, Chen J (2013) F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery. Biomaterials 34(4):1135–1145
Jiang L, Duan H, Ji X, Wang T, Wang Y, Qiu J (2018) Application of a simple desolvation method to increase the formation yield, physical stability and hydrophobic drug encapsulation capacity of chitosan-based nanoparticles. Int J Pharm 545(1–2):117–127
Kalluri A, Debnath D, Dharmadhikari B, Patra P (2018) Graphene quantum dots: synthesis and applications. Methods Enzymol 609:335–354
Li K, Zhao X, Wei G, Su Z (2018) Recent advances in the cancer bioimaging with graphene quantum dots. Curr Med Chem 25(25):2876–2893
Lin CY, Yang CM (2019) Study on the dissolution of hollow mesoporous silica nanosphere-supported nanosized platinum oxide in biorelevant media for evaluating its potential as chemotherapeutics. J Colloid Interface Sci 558:137–144
Luo P, Guan X, Yu Y, Li X, Yan F (2019) Hydrothermal synthesis of graphene quantum dots supported on three-dimensional graphene for supercapacitors. Nanomaterials (Basel) 9(2):201
National Research Council, Guide for the care and use of laboratory animals, The National Academies Press, Washington, DC, 8th edn, 2011
Numata K, Reagan MR, Goldstein RH, Rosenblatt M, Kaplan DL (2011) Spider silk-based gene carriers for tumor cell-specific delivery. Bioconjug Chem 22(8):1605–1610
Ren J, Fang Z, Yao L, Dahmani FZ, Yin L, Zhou J, Yao J (2015) A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery. Int J Pharm 487(1–2):177–186
Wan X, Liu C, Lin Y, Fu J, Lu G, Lu Z (2019) pH sensitive peptide functionalized nanoparticles for co-delivery of erlotinib and DAPT to restrict the progress of triple negative breast cancer. Drug Deliv 26(1):470–480
Yan Y, Gong J, Chen J, Zeng Z, Huang W, Pu K, Liu J, Chen P (2019) Recent advances on graphene quantum dots: from chemistry and physics to applications. Adv Mater 31(21):e1808283
Yang D, Yao X, Dong J, Wang N, Du Y, Sun S, Gao L, Zhong Y, Qian C, Hong H (2018) Design and investigation of core/shell GQDs/hMSN nanoparticles as an enhanced drug delivery platform in triple-negative breast cancer. Bioconjug Chem 29(8):2776–2785
Zhao Z, Wang Y, Han J, Wang K, Yang D, Yang Y, Du Q, Song Y, Yin X (2014) Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery. Int J Nanomedicine 9:5849–5862
Zhang Y, Wang H, Li C, Sun B, Wang Y, Wang S, Gao C (2014) A novel three-dimensional large-pore mesoporous carbon matrix as a potential nanovehicle for the fast release of the poorly water-soluble drug, celecoxib. Pharm Res 31(4):1059–1070
Zhang Y, Zhu W, Zhang H, Han J, Zhang L, Lin Q, Ai F (2017) Carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanoparticles with pH-responsive and prolonged release properties for oral delivery of the antitumor drug, docetaxel. Int J Pharm 532(1):384–392
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This work is supported by Natural Science Foundation of Jiangsu Province, China (BK20161173), and Xuzhou Natural Science Foundation, China (KC18201, KC18108 and KC19066).
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Yao, X., Qian, C., Zhong, Y. et al. In vivo targeting of breast cancer with peptide functionalized GQDs/hMSN nanoplatform. J Nanopart Res 21, 263 (2019). https://doi.org/10.1007/s11051-019-4700-5
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DOI: https://doi.org/10.1007/s11051-019-4700-5