SCIENCE CHINA Chemistry, Volume 60, Issue 9: 1219-1229(2017) https://doi.org/10.1007/s11426-017-9088-x

Synthesis of different-sized gold nanostars for Raman bioimaging and photothermal therapy in cancer nanotheranostics

More info
  • ReceivedApr 10, 2017
  • AcceptedMay 23, 2017
  • PublishedJul 28, 2017


Gold nanoparticles (AuNPs) have been attractive for nanomedicine because of their pronounced optical properties. Here, we customerized the methods to synthesize two types of gold nanostars, Au nanostars-1 and Au nanostars-2, which have different spire lengths and optical properties, and also spherical AuNPs. Compared to nanospheres, gold nanostars were less toxic to a variety of cells, including macrophages. Au nanostars-1 and Au nanostars-2 also manifested a similar pattern of tissue distribution upon in vivo administration in mice to that of nanospheres, and but reveled less liver retention than nanospheres. Due to their strong absorption in the near-infrared (NIR), Au nanostars-2 induced a strong hyperthermia effect in vitro upon excitation at 808 nm, and elicited a robust photothermal therapy (PTT) efficacy in ablating tumors in a mouse model of orthotopic breast cancer using 4T1 breast cancer cells. Meanwhile, Au nanostars-1 showed a great capability to enhance the Raman signal through surface-enhanced Raman spectroscopy (SERS) in 4T1 cells. Our combined results opened a new avenue to develop Au nanostars for cancer imaging and therapy.

Funded by

National Basic Research Program(2014CB932000)

Strategic Priority Research Program of the Chinese Academy of Sciences(XDB14000000)

National Natural Science Foundation of China(21425731,21637004)


This work was supported by the National Basic Research Program (2014CB932000), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB14000000) and the National Natural Science Foundation of China (21425731, 21637004).

Interest statement

The authors declare that they have no conflict of interest.


[1] Kim JE, Choi JH, Colas M, Kim DH, Lee H. Biosens Bioelectron, 2016, 80: 543-559 CrossRef PubMed Google Scholar

[2] Yang X, Yang M, Pang B, Vara M, Xia Y. Chem Rev, 2015, 115: 10410-10488 CrossRef PubMed Google Scholar

[3] Huang X, Jain PK, El-Sayed IH, El-Sayed MA. Lasers Med Sci, 2008, 23: 217-228 CrossRef PubMed Google Scholar

[4] Zhou H, Qiu C, Yu F, Yang H, Chen M, Hu L, Sun L. J Phys Chem C, 2011, 115: 11348-11354 CrossRef Google Scholar

[5] Tąta A, Szkudlarek A, Kim Y, Proniewicz E. Spectrochim Acta A-Mol Biomol Spectrosc, 2017, 173: 251-256 CrossRef PubMed ADS Google Scholar

[6] Liu XL, Liang S, Nan F, Yang ZJ, Yu XF, Zhou L, Hao ZH, Wang QQ. Nanoscale, 2013, 5: 5368-5374 CrossRef PubMed ADS Google Scholar

[7] Palonpon AF, Ando J, Yamakoshi H, Dodo K, Sodeoka M, Kawata S, Fujita K. Nat Protoc, 2013, 8: 677-692 CrossRef PubMed Google Scholar

[8] Weissleder R, Nahrendorf M, Pittet MJ. Nat Mater, 2014, 13: 125-138 CrossRef PubMed ADS Google Scholar

[9] Ju HX. Sci China Chem, 2011, 54: 1202-1217 CrossRef Google Scholar

[10] Wang P, Wan Y, Ali A, Deng S, Su Y, Fan C, Yang S. Sci China Chem, 2016, 59: 237-242 CrossRef Google Scholar

[11] Feng B, Zhou F, Wang D, Xu Z, Yu H, Li Y. Sci China Chem, 2016, 59: 984-990 CrossRef Google Scholar

[12] Alkilany AM, Nagaria PK, Hexel CR, Shaw TJ, Murphy CJ, Wyatt MD. Small, 2009, 5: 701-708 CrossRef PubMed Google Scholar

[13] Kumar PS, Pastoriza-Santos I, Rodriguez-Gonzalez B, Garcia de Abajo FJ, Liz-Marzan LM. Nanotechnology, 2007, 19: 015606. Google Scholar

[14] Zhou CH, Gan LL, Zhang YY, Zhang FF, Wang GZ, Jin L, Geng RX. Sci China Ser B-Chem, 2009, 52: 415-458 CrossRef Google Scholar

[15] Song HM, Wei Q, Ong QK, Wei A. ACS Nano, 2010, 4: 5163-5173 CrossRef PubMed Google Scholar

[16] Fales AM, Yuan H, Vo-Dinh T. Langmuir, 2011, 27: 12186-12190 CrossRef PubMed Google Scholar

[17] Yu J, Guo WC, Yang M, Luan Y, Tao JZ, Zhang XW. Sci China Chem, 2014, 57: 1211-1217 CrossRef Google Scholar

[18] Rodríguez-Lorenzo L, Krpetic Z, Barbosa S, Alvarez-Puebla RA, Liz-Marzán LM, Prior IA, Brust M. Integr Biol, 2011, 3: 922-926 CrossRef PubMed Google Scholar

[19] Jimenez de Aberasturi D, Serrano-Montes AB, Langer J, Henriksen-Lacey M, Parak WJ, Liz-Marzán LM. Chem Mater, 2016, 28: 6779-6790 CrossRef Google Scholar

[20] Vendrell M, Maiti KK, Dhaliwal K, Chang YT. Trends Biotech, 2013, 31: 249-257 CrossRef PubMed Google Scholar

[21] Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, Chan WCW. Nat Rev Mater, 2016, 1: 16014 CrossRef ADS Google Scholar

[22] Khlebtsov N, Dykman L. Chem Soc Rev, 2011, 40: 1647-1671 CrossRef PubMed Google Scholar

[23] Yen HJ, Hsu SH, Tsai CL. Small, 2009, 5: 1553-1561 CrossRef PubMed Google Scholar

[24] Sun YN, Wang CD, Zhang XM, Ren L, Tian XH. J Nanosci Nanotech, 2011, 11: 1210-1216 CrossRef Google Scholar

[25] Kah JCY, Grabinski C, Untener E, Garrett C, Chen J, Zhu D, Hussain SM, Hamad-Schifferli K. ACS Nano, 2014, 8: 4608-4620 CrossRef PubMed Google Scholar

[26] Chen Y, Wang Z, Xu M, Wang X, Liu R, Liu Q, Zhang Z, Xia T, Zhao J, Jiang G, Xu Y, Liu S. ACS Nano, 2014, 8: 5813-5825 CrossRef PubMed Google Scholar

[27] Guo W, Zhang S, Chen Y, Zhang D, Yuan L, Cong H, Liu S. Acta Biochim Biophys Sin, 2015, 47: 703-715 CrossRef PubMed Google Scholar

[28] Guo W, Zhang S, Liu S. Oncol Rep, 2015, 33: 2992-2998 CrossRef PubMed Google Scholar

[29] de Puig H, Tam JO, Yen CW, Gehrke L, Hamad-Schifferli K. J Phys Chem C, 2015, 119: 17408-17415 CrossRef PubMed Google Scholar

[30] Ma J, Li R, Qu G, Liu H, Yan B, Xia T, Liu Y, Liu S. Nanoscale, 2016, 8: 18070-18086 CrossRef PubMed Google Scholar

[31] Ma J, Liu R, Wang X, Liu Q, Chen Y, Valle RP, Zuo YY, Xia T, Liu S. ACS Nano, 2015, 9: 10498-10515 CrossRef Google Scholar

[32] Mosmann T. J Immunol Methods, 1983, 65: 55-63 CrossRef Google Scholar

[33] Su YH, Ke YF, Cai SL, Yao QY. Light Sci Appl, 2012, 1: e14 CrossRef Google Scholar

[34] Adair JH, Parette MP, Altınoğlu EI, Kester M. ACS Nano, 2010, 4: 4967-4970 CrossRef PubMed Google Scholar

[35] Chithrani BD, Ghazani AA, Chan WCW. Nano Lett, 2006, 6: 662-668 CrossRef PubMed ADS Google Scholar

[36] Vácha R, Martinez-Veracoechea FJ, Frenkel D. Nano Lett, 2011, 11: 5391-5395 CrossRef PubMed Google Scholar

[37] Ferrari M. Nat Rev Cancer, 2005, 5: 161-171 CrossRef PubMed Google Scholar

[38] Lacerda SHDP, Park JJ, Meuse C, Pristinski D, Becker ML, Karim A, Douglas JF. ACS Nano, 2010, 4: 365-379 CrossRef PubMed Google Scholar

[39] Cigler P, Lytton-Jean AKR, Anderson DG, Finn MG, Park SY. Nat Mater, 2010, 9: 918-922 CrossRef PubMed ADS Google Scholar

[40] Tian M, Ogawa K, Wendt R, Mukhopadhyay U, Balatoni J, Fukumitsu N, Uthamanthil R, Borne A, Brammer D, Jackson J, Mawlawi O, Yang B, Alauddin MM, Gelovani JG. J Nucl Med, 2011, 52: 934-941 CrossRef PubMed Google Scholar

[41] Kreyling WG, Abdelmonem AM, Ali Z, Alves F, Geiser M, Haberl N, Hartmann R, Hirn S, de Aberasturi DJ, Kantner K, Khadem-Saba G, Montenegro JM, Rejman J, Rojo T, de Larramendi IR, Ufartes R, Wenk A, Parak WJ. Nat Nanotech, 2015, 10: 619-623 CrossRef PubMed ADS Google Scholar

[42] Liang S, Li C, Zhang C, Chen Y, Xu L, Bao C, Wang X, Liu G, Zhang F, Cui D. Theranostics, 2015, 5: 970-984 CrossRef PubMed Google Scholar

[43] Liu J, Zheng X, Gu Z, Chen C, Zhao Y. Nanomed-Nanotechnol Biol Med, 2016, 12: 486-487 CrossRef Google Scholar

[44] Liu J, Zheng X, Yan L, Zhou L, Tian G, Yin W, Wang L, Liu Y, Hu Z, Gu Z, Chen C, Zhao Y. ACS Nano, 2015, 9: 696-707 CrossRef PubMed Google Scholar

[45] Wang S, Shang L, Li L, Yu Y, Chi C, Wang K, Zhang J, Shi R, Shen H, Waterhouse GIN, Liu S, Tian J, Zhang T, Liu H. Adv Mater, 2016, 28: 8379-8387 CrossRef PubMed Google Scholar

[46] Liu Y, Ai K, Liu J, Deng M, He Y, Lu L. Adv Mater, 2013, 25: 1353-1359 CrossRef PubMed Google Scholar

[47] Liu H, Liu T, Wu X, Li L, Tan L, Chen D, Tang F. Adv Mater, 2012, 24: 755-761 CrossRef PubMed Google Scholar

[48] Liu J, Wang P, Zhang X, Wang L, Wang D, Gu Z, Tang J, Guo M, Cao M, Zhou H, Liu Y, Chen C. ACS Nano, 2016, 10: 4587-4598 CrossRef Google Scholar

[49] Ren W, Liu JY, Guo SJ, Wang EK. Sci China Chem, 2011, 54: 1334-1341 CrossRef Google Scholar

[50] Tong LM, Zhu T, Liu ZF. Sci China Ser B, 2007, 50: 520-525 CrossRef Google Scholar

[51] Indrasekara ASDS, Meyers S, Shubeita S, Feldman LC, Gustafsson T, Fabris L. Nanoscale, 2014, 6: 8891-8899 CrossRef PubMed ADS Google Scholar

[52] Tian F, Bonnier F, Casey A, Shanahan AE, Byrne HJ. Anal Methods, 2014, 6: 9116-9123 CrossRef Google Scholar

[53] Song C, Yang B, Yang Y, Wang L. Sci China Chem, 2016, 59: 16-29 CrossRef Google Scholar

[54] Michota A, Bukowska J. J Raman Spectrosc, 2003, 34: 21-25 CrossRef ADS Google Scholar

  • Figure 1

    Physical characterization of AuNPs. (a) TEM images of Au nanostars-1, Au nanostars-2 and Au nanospheres; (b) hydrodynamic diameters of AuNPs measured by DLS; (c) zeta-potentials of AuNPs solutions; (d) UV-Vis spectra of Au nanostars-1, Au nanostars-2 and Au nanospheres in water (color online).

  • Figure 2

    Cytotoxicity evaluation upon AuNPs in J774A.1 cells. (a) Cell viability determined by the MTT assay in J774A.1 cells upon exposure to AuNPs at 1, 10 and 20 μg/mL for 24 h (n=6); (b) relative LDH release in J774A.1 cells treated with AuNPs for 24 h (n=6); (c) cellular energy metabolism in J774A.1 cells, as characterized by ATP production, in response to AuNPs for 24 h. Cellular ATP mass was assayed by the bioluminescent intensity on a microplate reader and relative ATP levels were quantified by normalizing to the untreated control (n=6) (color online).

  • Figure 3

    Cytotoxicity determination in 4T1 cells responded to AuNPs. (a) Cytotoxicity determined by the MTT assay in 4T1 cells treated with AuNPs at concentrations of 1, 10 and 20 μg/mL for 24 h (n=6); (b) ATP production in 4T1 cells upon AuNPs for 24 h (n=6); (c) ATP production levels quantified after cells were treated with AuNPs at various concentrations for 24 h (n=6). Arrows represent the drop, compared to untreated control: one arrow, 20% reduction; two arrows, ~40% reduction; three arrows, ~60% reduction (color online).

  • Figure 4

    Cellular uptake and the localization of AuNPs. (a) Quantification of the amount of elemental Au in cells by ICP-MS in J774.1A cells after 24-h incubation with 10 μg/mL AuNPs (n=6); (b) TEM images of J774.1A cells post treatment with AuNPs. After incubation with 10 μg/mL Au nanostars-1 and Au nanospheres for 24 h, cells were collected for TEM analysis of intracellular AuNPs. Blue arrows denote nanoparticles, and red arrows indicate phagosomes (color online).

  • Figure 5

    Biodistrbution and histological examinations of tissues upon AuNPs in vivo. (a) Biodistribution of AuNPs in various organs in mice after AuNPs administration at 10 μg/mouse for 24 h. (b) H&E staining of various tissues from mice administrated with AuNPs at 10 μg/mice for 24 h. Original magnification, ×100 (color online).

  • Figure 6

    The photothermal effect of Au nanostars-1 in vitro. (a) The photothermal effect curve of the temperature of an Au nanostars-1 solution in water under NIR irradiation for 10 min; (b) cytotoxicity of 4T1 cells at the different concentrations of Au nanostars-1 with or without NIR determined by the MTT assay (n=6) (color online).

  • Figure 7

    Hyperthermia effect and photothermal ablation of tumors in mice. (a) Laser irradiation temperature elevation in 4T1 tumors implanted in mice after injection of nanostars-1. The temperature was recorded at different time intervals after material injection. (b) The tumor growth curves in mice upon PTT with nanostars-1 over the time course (n=3). (c) The alterations of body weight of mice upon PTT with nanostars-1 over time (n=3). (d) The representative images of tumors post PTT at different time times post injection (color online).

  • Figure 8

    Raman spectra of nanostars-1 in 4T1 cells. (a) Raman spectra of Au nanostars-1 and Au nanospheres incubated with 4-MBA overnight; (b, c) a representative Raman bright-field image of a 4T1 cell after exposure to with nanostars-1-MBA for 24 h was selected for streamline mapping and the corresponding Raman spectra. Points 1‒4 indicated different locations inside or outside of the selected cell (color online).

Copyright 2020 Science China Press Co., Ltd. 《中国科学》杂志社有限责任公司 版权所有