Nano Research

, Volume 12, Issue 4, pp 719–732 | Cite as

Functionalization of AuMSS nanorods towards more effective cancer therapies

  • Carolina F. Rodrigues
  • Telma A. Jacinto
  • André F. Moreira
  • Elisabete C. Costa
  • Sónia P. Miguel
  • Ilídio J. CorreiaEmail author
Review Article


The application of nanoparticles as selective drug delivery platforms arises as one the most promising therapeutic strategies in the biomedical field. Such systems can encapsulate drugs, prevent its premature degradation, transport and promote the drugs specific delivery to the target site. Among the different nanostructures, gold-core mesoporous silica shell (AuMSS) nanorods have been one of the most explored due to their unique physical and chemical properties. The mesoporous silica biocompatibility, high surface area that can be easily functionalized, tubular pores that can store the drugs, conjugated with the intrinsic capacity of gold nanorod to absorb near-infrared radiation, allows the combination of hyperthermia (i.e., photothermal effect) with drug delivery, making them a nanoplatforms with a huge potential for cancer therapy. Nevertheless, the successful application of AuMSS nanoparticles as an effective cancer nanomedicine is hindered by the uncontrolled release of the therapeutic payloads, limited blood circulation time and unfavorable pharmacokinetics.

In this review, an overview of the modifications performed to improve the AuMSS nanorods application in nanomedicine is provided, highlighting the practical approaches that enhanced the AuMSS nanorods targeting, responsiveness to different stimuli, and blood circulation time. Further, the basics of AuMSS nanorods synthesis procedures, general properties, and its application in cancer therapy are also described.


gold nanorods silica surface modifications targeting cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This work was supported by FEDER funds through the POCI— COMPETE 2020—Operational Programme Competitiveness and Internationalisation in Axis I—Strengthening research, technological development and innovation (Project POCI-01—0145-FEDER-007491) and National Funds by FCT—Foundation for Science and Technology (Project UID/Multi/00709/2013). A. F. M., S. P. M., and E. C. C. acknowledges their Ph.D. fellowships from FCT (Nos. SFRH/BD/ 109482/2015, SFRH/BD/109563/2015, and SFRH/BD/103507/2014).


  1. [1]
    Pelaz B.; Alexiou C.; Alvarez-Puebla R. A.; Alves F.; Andrews A. M.; Ashraf S.; Balogh L. P.; Ballerini L.; Bestetti A.; Brendel C. et al. Diverse applications of nanomedicine. ACS Nano 2017, 11, 2313–2381.Google Scholar
  2. [2]
    Loureiro J. A.; Gomes B.; Fricker G.; Coelho M. A. N.; Rocha S.; Pereira M. C. Cellular uptake of PLGA nanoparticles targeted with antiamyloid and anti-transferrin receptor antibodies for Alzheimer’s disease treatment. Colloids Surf. B Biointerfaces 2016, 145, 8–13.Google Scholar
  3. [3]
    Wang N.; Jin X.; Guo D. B.; Tong G. S.; Zhu X. Y. Iron chelation nanoparticles with delayed saturation as an effective therapy for Parkinson disease. Biomacromolecules 2016, 18, 461–474.Google Scholar
  4. [4]
    Moreira A. F.; Gaspar V. M.; Costa E. C.; de Melo-Diogo D.; Machado P.; Paquete C. M.; Correia I. J. Preparation of end-capped pH-sensitive mesoporous silica nanocarriers for on-demand drug delivery. Eur. J. Pharm. Biopharm. 2014, 88, 1012–1025.Google Scholar
  5. [5]
    Moreira A. F.; Dias D. R.; Correia I. J. Stimuli-responsive mesoporous silica nanoparticles for cancer therapy: A review. Microporous Mesoporous Mater. 2016, 236, 141–157.Google Scholar
  6. [6]
    Brannon-Peppas L.; Blanchette J. O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Delivery Rev. 2012, 64, 206–212.Google Scholar
  7. [7]
    Abbas M.; Zou Q. L.; Li S. K.; Yan X. H. Self-assembled peptide- and protein-based nanomaterials for antitumor photodynamic and photothermal therapy. Adv. Mater. 2017, 29, 1605021.Google Scholar
  8. [8]
    Moreira A. F.; Rodrigues C. F.; Reis C. A.; Costa E. C.; Correia I. J. Gold-core silica shell nanoparticles application in imaging and therapy: A review. Microporous Mesoporous Mater. 2018, 270, 168–179.Google Scholar
  9. [9]
    Huff T. B.; Tong L.; Zhao Y.; Hansen M. N.; Cheng J. X.; Wei A. Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2007, 2, 125–132.Google Scholar
  10. [10]
    Hemmer E.; Benayas A.; Légaré F.; Vetrone F. Exploiting the biological windows: Current perspectives on fluorescent bioprobes emitting above 1,000 nm. Nanoscale Horiz. 2016, 1, 168–184.Google Scholar
  11. [11]
    Yao X. X.; Niu X. X.; Ma K. X.; Huang P.; Grothe J.; Kaskel S.; Zhu Y. F. Graphene quantum dots-capped magnetic mesoporous silica nanoparticles as a multifunctional platform for controlled drug delivery, magnetic hyperthermia, and photothermal therapy. Small 2017, 13, 1602225.Google Scholar
  12. [12]
    Li Y. T.; Jin J.; Wang D. W.; Lv J. W.; Hou K.; Liu Y. L.; Chen C. Y.; Tang Z. Y. Coordination-responsive drug release inside gold nanorod@metalorganic framework core–shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy. Nano Res. 2018, 11, 3294–3305.Google Scholar
  13. [13]
    Jiang Y. Y.; Cui D.; Fang Y.; Zhen X.; Upputuri P. K.; Pramanik M.; Ding D.; Pu K. Y. Amphiphilic semiconducting polymer as multifunctional nanocarrier for fluorescence/photoacoustic imaging guided chemophotothermal therapy. Biomaterials 2017, 145, 168–177.Google Scholar
  14. [14]
    Cheng X. J.; Sun R.; Yin L.; Chai Z. F.; Shi H. B.; Gao M. Y. Lighttriggered assembly of gold nanoparticles for photothermal therapy and photoacoustic imaging of tumors in vivo. Adv. Mater. 2017, 29, 1604894.Google Scholar
  15. [15]
    Kim H. S.; Lee D. Y. Photothermal therapy with gold nanoparticles as an anticancer medication. J. Pharm. Invest. 2017, 47, 19–26.Google Scholar
  16. [16]
    Dias D. R.; Moreira A. F.; Correia I. J. The effect of the shape of gold core–mesoporous silica shell nanoparticles on the cellular behavior and tumor spheroid penetration. J. Mater. Chem. B 2016, 4, 7630–7640.Google Scholar
  17. [17]
    Wang S. W.; Xi W.; Cai F. H.; Zhao X. Y.; Xu Z. P.; Qian J.; He S. L. Three-photon luminescence of gold nanorods and its applications for high contrast tissue and deep in vivo brain imaging. Theranostics 2015, 5, 251–266.Google Scholar
  18. [18]
    Chen J. Y.; Wang D. L.; Xi J. F.; Au L.; Siekkinen A.; Warsen A.; Li Z. Y.; Zhang H.; Xia Y. N.; Li X. D. Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. Nano Lett. 2007, 7, 1318–1322.Google Scholar
  19. [19]
    Yuan H.; Fales A. M.; Vo-Dinh T. TAT peptide-functionalized gold nanostars: Enhanced intracellular delivery and efficient NIR photothermal therapy using ultralow irradiance. J. Am. Chem. Soc. 2012, 134, 11358–11361.Google Scholar
  20. [20]
    Han L.; Zhang Y.; Zhang Y.; Shu Y.; Chen X. W.; Wang J. H. A magnetic polypyrrole/iron oxide core/gold shell nanocomposite for multimodal imaging and photothermal cancer therapy. Talanta 2017, 171, 32–38.Google Scholar
  21. [21]
    Yang X.; Yang M. X.; Pang B.; Vara M.; Xia Y. N. Gold nanomaterials at work in biomedicine. Chem. Rev. 2015, 115, 10410–10488.Google Scholar
  22. [22]
    Boisselier E.; Astruc D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem. Soc. Rev. 2009, 38, 1759–1782.Google Scholar
  23. [23]
    Li Z. T.; Zhu Z. M.; Liu W. J.; Zhou Y. L.; Han B.; Gao Y.; Tang Z. Y. Reversible plasmonic circular dichroism of Au nanorod and DNA assemblies. J. Am. Chem. Soc. 2012, 134, 3322–3325.Google Scholar
  24. [24]
    Love J. C.; Estroff L. A.; Kriebel J. K.; Nuzzo R. G.; Whitesides G. M. Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem. Rev. 2005, 105, 1103–1170.Google Scholar
  25. [25]
    Liu J. Y.; Peng Q. Protein-gold nanoparticle interactions and their possible impact on biomedical applications. Acta Biomater. 2017, 55, 13–27.Google Scholar
  26. [26]
    Aggarwal P.; Hall J. B.; McLeland C. B.; Dobrovolskaia M. A.; McNeil S. E. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv. Drug Delivery Rev. 2009, 61, 428–437.Google Scholar
  27. [27]
    Lynch I.; Dawson K. A. Protein-nanoparticle interactions. Nano Today 2008, 3, 40–47.Google Scholar
  28. [28]
    Chen Y. S.; Frey W.; Kim S.; Homan K.; Kruizinga P.; Sokolov K.; Emelianov S. Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. Opt. Express 2010, 18, 8867–8878.Google Scholar
  29. [29]
    Tang F. Q.; Li L. L.; Chen D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.Google Scholar
  30. [30]
    Pan L. M.; He Q. J.; Liu J. N.; Chen Y.; Ma M.; Zhang L. L.; Shi J. L. Nuclear-targeted drug delivery of TAT peptide-conjugated monodisperse mesoporous silica nanoparticles. J. Am. Chem. Soc. 2012, 134, 5722–5725.Google Scholar
  31. [31]
    Song J. T.; Yang X. Q.; Zhang X. S.; Yan D. M.; Wang Z. Y.; Zhao Y. D. Facile synthesis of gold nanospheres modified by positively charged mesoporous silica, loaded with near-infrared fluorescent dye, for in vivo X-ray computed tomography and fluorescence dual mode imaging. ACS Appl. Mater. Interfaces 2015, 7, 17287–17297.Google Scholar
  32. [32]
    Liu S. H.; Han M. Y. Synthesis, functionalization, and bioconjugation of monodisperse, silica-coated gold nanoparticles: Robust bioprobes. Adv. Funct. Mater. 2005, 15, 961–967.Google Scholar
  33. [33]
    Wu W. C.; Tracy J. B. Large-scale silica overcoating of gold nanorods with tunable shell thicknesses. Chem. Mater. 2015, 27, 2888–2894.Google Scholar
  34. [34]
    Tran A. V.; Shim K.; Thi T. T. V.; Kook J. K.; An S. S. A.; Lee S. W. Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers. Acta Biomater. 2018, 74, 397–413.Google Scholar
  35. [35]
    Zhao P. Q.; Li L. F.; Zhou S. Y.; Qiu L. H.; Qian Z. Z.; Liu X. M.; Cao X. C.; Zhang H. L. TPGS functionalized mesoporous silica nanoparticles for anticancer drug delivery to overcome multidrug resistance. Mater. Sci. Eng. C 2018, 84, 108–117.Google Scholar
  36. [36]
    Xu C.; Chen F.; Valdovinos H. F.; Jiang D. W.; Goel S.; Yu B.; Sun H. Y.; Barnhart T. E.; Moon J. J.; Cai W. B. Bacteria-like mesoporous silicacoated gold nanorods for positron emission tomography and photoacoustic imaging-guided chemo-photothermal combined therapy. Biomaterials 2018, 165, 56–65.Google Scholar
  37. [37]
    Liu Y.; Xu M.; Chen Q.; Guan G. N.; Hu W.; Zhao X. L.; Qiao M. X.; Hu H. Y.; Liang Y.; Zhu H. Y. et al. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser. Int. J. Nanomedicine 2015, 10, 4747–4761.Google Scholar
  38. [38]
    Qin J. B.; Peng Z. Y.; Li B.; Ye K. C.; Zhang Y. X.; Yuan F. K.; Yang X. R.; Huang L. J.; Hu J. Q.; Lu X. W. Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages. Nanoscale 2015, 7, 13991–14001.Google Scholar
  39. [39]
    Dreaden E. C.; Alkilany A. M.; Huang X. H.; Murphy C. J.; El-Sayed M. A. The golden age: Gold nanoparticles for biomedicine. Chem. Soc. Rev. 2012, 41, 2740–2779.Google Scholar
  40. [40]
    Nikoobakht B.; El-Sayed M. A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem. Mater. 2003, 15, 1957–1962.Google Scholar
  41. [41]
    Johnson C. J.; Dujardin E.; Davis S. A.; Murphy C. J.; Mann S. Growth and form of gold nanorods prepared by seed-mediated, surfactant-directed synthesis. J. Mater. Chem. 2002, 12, 1765–1770.Google Scholar
  42. [42]
    Gole A.; Murphy C. J. Seed-mediated synthesis of gold nanorods: Role of the size and nature of the seed. Chem. Mater. 2004, 16, 3633–3640.Google Scholar
  43. [43]
    Zhao P. X.; Li N.; Astruc D. State of the art in gold nanoparticle synthesis. Coord. Chem. Rev. 2013, 257, 638–665.Google Scholar
  44. [44]
    Liu M. Z.; Guyot-Sionnest P. Mechanism of silver(I)-assisted growth of gold nanorods and bipyramids. J. Phys. Chem. B 2005, 109, 22192–22200.Google Scholar
  45. [45]
    Pérez-Juste J.; Correa-Duarte M. A.; Liz-Marzán L. M. Silica gels with tailored, gold nanorod-driven optical functionalities. Appl. Surf. Sci. 2004, 226, 137–143.Google Scholar
  46. [46]
    Kobayashi Y.; Correa-Duarte M. A.; Liz-Marzán L. M. Sol-gel processing of silica-coated gold nanoparticles. Langmuir 2001, 17, 6375–6379.Google Scholar
  47. [47]
    Mine E.; Yamada A.; Kobayashi Y.; Konno M.; Liz-Marzán L. M. Direct coating of gold nanoparticles with silica by a seeded polymerization technique. J. Colloid Interface Sci. 2003, 264, 385–390.Google Scholar
  48. [48]
    Zhao N.; Yang Z. R.; Li B. X.; Meng J.; Shi Z. L.; Li P.; Fu S. RGDconjugated mesoporous silica-encapsulated gold nanorods enhance the sensitization of triple-negative breast cancer to megavoltage radiation therapy. Int. J. Nanomedicine 2016, 11, 5595–5610.Google Scholar
  49. [49]
    Hainfeld J. F.; Slatkin D. N.; Focella T. M.; Smilowitz H. M. Gold nanoparticles: A new X-ray contrast agent. Br. J. Radiol. 2006, 79, 248–253.Google Scholar
  50. [50]
    Hou K.; Fixler D.; Han B.; Shi L.; Feder I.; Duadi H.; Wang X. L.; Tang Z. Y. Towards in vivo tumor detection using polarization and wavelength characteristics of self-assembled gold nanorods. ChemNanoMat 2017, 3, 736–739.Google Scholar
  51. [51]
    Ashton J. R.; Castle K. D.; Qi Y.; Kirsch D. G.; West J. L.; Badea C. T. Dual-energy CT imaging of tumor liposome delivery after gold nanoparticleaugmented radiation therapy. Theranostics 2018, 8, 1782–1797.Google Scholar
  52. [52]
    Chen Q.; Wang H.; Liu H.; Wen S. H.; Peng C.; Shen M. W.; Zhang G. X.; Shi X. Y. Multifunctional dendrimer-entrapped gold nanoparticles modified with RGD peptide for targeted computed tomography/magnetic resonance dual-modal imaging of tumors. Anal. Chem. 2015, 87, 3949–3956.Google Scholar
  53. [53]
    Amendola V.; Pilot R.; Frasconi M.; Marago O. M.; Iati M. A. Surface plasmon resonance in gold nanoparticles: A review. J. Phys. Condens. Matter 2017, 29, 203002.Google Scholar
  54. [54]
    Shajari D.; Bahari A.; Gill P.; Mohseni M. Synthesis and tuning of gold nanorods with surface plasmon resonance. Opt. Mater. 2017, 64, 376–383.Google Scholar
  55. [55]
    Alkilany A. M.; Thompson L. B.; Boulos S. P.; Sisco P. N.; Murphy C. J. Gold nanorods: Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Adv. Drug Delivery Rev. 2012, 64, 190–199.Google Scholar
  56. [56]
    Nel A. E.; Mädler L.; Velegol D.; Xia T.; Hoek E. M. V.; Somasundaran P.; Klaessig F.; Castranova V.; Thompson M. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater. 2009, 8, 543–557.Google Scholar
  57. [57]
    Walkey C. D.; Olsen J. B.; Guo H. B.; Emili A.; Chan W. C. W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 2012, 134, 2139–2147.Google Scholar
  58. [58]
    Lee Y. K.; Choi E. J.; Webster T. J.; Kim S. H.; Khang D. Effect of the protein corona on nanoparticles for modulating cytotoxicity and immunotoxicity. Int. J. Nanomedicine 2015, 10, 97–113.Google Scholar
  59. [59]
    Kharazian B.; Hadipour N. L.; Ejtehadi M. R. Understanding the nanoparticle–protein corona complexes using computational and experimental methods. Int. J. Biochem. Cell Biol. 2016, 75, 162–174.Google Scholar
  60. [60]
    Bertrand N.; Grenier P.; Mahmoudi M.; Lima E. M.; Appel E. A.; Dormont F.; Lim J. M.; Karnik R.; Langer R.; Farokhzad O. C. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nat. Commun. 2017, 8, 777.Google Scholar
  61. [61]
    Steichen S. D.; Caldorera-Moore M.; Peppas N. A. A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur. J. Pharm. Sci. 2013, 48, 416–427.Google Scholar
  62. [62]
    Otsuka H.; Nagasaki Y.; Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Adv. Drug Delivery Rev. 2012, 64, 246–255.Google Scholar
  63. [63]
    Knop K.; Hoogenboom R.; Fischer D.; Schubert U. S. Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives. Angew. Chem., Int. Ed. 2010, 49, 6288–6308.Google Scholar
  64. [64]
    Kolate A.; Baradia D.; Patil S.; Vhora I.; Kore G.; Misra A. PEG—A versatile conjugating ligand for drugs and drug delivery systems. J. Control. Release 2014, 192, 67–81.Google Scholar
  65. [65]
    Delgado C.; Francis G. E.; Fisher D. The uses and properties of PEGlinked proteins. Crit. Rev. Ther. Drug Carrier Syst. 1992, 9, 249–304.Google Scholar
  66. [66]
    Fang C.; Bhattarai N.; Sun C.; Zhang M. Q. Functionalized nanoparticles with long-term stability in biological media. Small 2009, 5, 1637–1641.Google Scholar
  67. [67]
    Pozzi D.; Colapicchioni V.; Caracciolo G.; Piovesana S.; Capriotti A. L.; Palchetti S.; De Grossi S.; Riccioli A.; Amenitsch H.; Laganà A. Effect of polyethyleneglycol (PEG) chain length on the bio-nano-interactions between PEGylated lipid nanoparticles and biological fluids: From nanostructure to uptake in cancer cells. Nanoscale 2014, 6, 2782–2792.Google Scholar
  68. [68]
    Owens III D. E.; Peppas N. A. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int. J. Pharm. 2006, 307, 93–102.Google Scholar
  69. [69]
    Suk J. S.; Xu Q. G.; Kim N.; Hanes J.; Ensign L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Delivery Rev. 2016, 99, 28–51.Google Scholar
  70. [70]
    DeRouchey J.; Walker G. F.; Wagner E.; Rädler J. O. Decorated rods: A “bottom-up” self-assembly of monomolecular DNA complexes. J. Phys. Chem. B 2006, 110, 4548–4554.Google Scholar
  71. [71]
    Yang Q.; Jones S. W.; Parker C. L.; Zamboni W. C.; Bear J. E.; Lai S. K. Evading immune cell uptake and clearance requires PEG grafting at densities substantially exceeding the minimum for brush conformation. Mol. Pharm. 2014, 11, 1250–1258.Google Scholar
  72. [72]
    Shen S.; Tang H. Y.; Zhang X. T.; Ren J. F.; Pang Z. Q.; Wang D. G.; Gao H. L.; Qian Y.; Jiang X. G.; Yang W. L. Targeting mesoporous silica-encapsulated gold nanorods for chemo-photothermal therapy with near-infrared radiation. Biomaterials 2013, 34, 3150–3158.Google Scholar
  73. [73]
    Wang J.; Bai R.; Yang R.; Liu J.; Tang J. L.; Liu Y.; Li J. Y.; Chai Z. F.; Chen C. Y. Size- and surface chemistry-dependent pharmacokinetics and tumor accumulation of engineered gold nanoparticles after intravenous administration. Metallomics 2015, 7, 516–524.Google Scholar
  74. [74]
    Liu J. J.; Liang H. N.; Li M. H.; Luo Z.; Zhang J. X.; Guo X. M.; Cai K. Y. Tumor acidity activating multifunctional nanoplatform for NIRmediated multiple enhanced photodynamic and photothermal tumor therapy. Biomaterials 2018, 157, 107–124.Google Scholar
  75. [75]
    Ishida T.; Atobe K.; Wang X. Y.; Kiwada H. Accelerated blood clearance of PEGylated liposomes upon repeated injections: Effect of doxorubicinencapsulation and high-dose first injection. J. Control. Release 2006, 115, 251–258.Google Scholar
  76. [76]
    Lila A. S. A.; Kiwada H.; Ishida T. The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage. J. Control. Release 2013, 172, 38–47.Google Scholar
  77. [77]
    Konradi R.; Pidhatika B.; Mühlebach A.; Textor M. Poly-2-methyl-2- oxazoline: A peptide-like polymer for protein-repellent surfaces. Langmuir 2008, 24, 613–616.Google Scholar
  78. [78]
    Mero A.; Pasut G.; Dalla Via L.; Fijten M. W. M.; Schubert U. S.; Hoogenboom R.; Veronese F. M. Synthesis and characterization of poly(2-ethyl-2-oxazoline)-conjugates with proteins and drugs: Suitable alternatives to PEG-conjugates? J. Control. Release 2008, 125, 87–95.Google Scholar
  79. [79]
    Koshkina O.; Westmeier D.; Lang T.; Bantz C.; Hahlbrock A.; Würth C.; Resch-Genger U.; Braun U.; Thiermann R.; Weise C. et al. Tuning the surface of nanoparticles: Impact of poly(2-ethyl-2-oxazoline) on protein adsorption in serum and cellular uptake. Macromol. Biosci. 2016, 16, 1287–1300.Google Scholar
  80. [80]
    Moreira A. F.; Rodrigues C. F.; Reis C. A.; Costa E. C.; Ferreira P.; Correia I. J. Development of poly-2-ethyl-2-oxazoline coated gold-core silica shell nanorods for cancer chemo-photothermal therapy. Nanomedicine 2018, 13, 3147–3166.Google Scholar
  81. [81]
    Moreira A. F.; Dias D. R.; Costa E. C.; Correia I. J. Thermo- and pH-responsive nano-in-micro particles for combinatorial drug delivery to cancer cells. Eur. J. Pharm. Sci. 2017, 104, 42–51.Google Scholar
  82. [82]
    Li Y. H.; Hu H.; Zhou Q.; Ao Y. X.; Xiao C.; Wan J. L.; Wan Y.; Xu H. B.; Li Z. F.; Yang X. L. α-Amylase-and redox-responsive nanoparticles for tumor-targeted drug delivery. ACS Appl. Mater. Interfaces 2017, 9, 19215–19230.Google Scholar
  83. [83]
    Zhang C. Y.; Pan D. Y.; Li J.; Hu J. N.; Bains A.; Guys N.; Zhu H. Y.; Li X. H.; Luo K.; Gong Q. Y. et al. Enzyme-responsive peptide dendrimergemcitabine conjugate as a controlled-release drug delivery vehicle with enhanced antitumor efficacy. Acta Biomater. 2017, 55, 153–162.Google Scholar
  84. [84]
    Li H.; Tan L. L.; Jia P.; Li Q. L.; Sun Y. L.; Zhang J.; Ning Y. Q.; Yu J. H.; Yang Y. W. Near-infrared light-responsive supramolecular nanovalve based on mesoporous silica-coated gold nanorods. Chem. Sci. 2014, 5, 2804–2808.Google Scholar
  85. [85]
    Liu J.; Detrembleur C.; De Pauw-Gillet M. C.; Mornet S.; Jérôme C.; Duguet E. Gold nanorods coated with mesoporous silica shell as drug delivery system for remote near infrared light-activated release and potential phototherapy. Small 2015, 11, 2323–2332.Google Scholar
  86. [86]
    Tang H. Y.; Shen S.; Guo J.; Chang B. S.; Jiang X. G.; Yang W. L. Gold nanorods@mSiO2 with a smart polymer shell responsive to heat/near-infrared light for chemo-photothermal therapy. J. Mater. Chem. 2012, 22, 16095–16103.Google Scholar
  87. [87]
    Lee E. S.; Gao Z. G.; Bae Y. H. Recent progress in tumor pH targeting nanotechnology. J. Control. Release 2008, 132, 164–170.Google Scholar
  88. [88]
    Du J. Z.; Lane L. A.; Nie S. M. Stimuli-responsive nanoparticles for targeting the tumor microenvironment. J. Control. Release 2015, 219, 205–214.Google Scholar
  89. [89]
    Vander Heiden M. G.; Cantley L. C.; Thompson C. B. Understanding the warburg effect: The metabolic requirements of cell proliferation. Science 2009, 324, 1029–1033.Google Scholar
  90. [90]
    Zhang T.; Ding Z. Y.; Lin H. M.; Cui L. R.; Yang C. Y.; Li X.; Niu H.; An N.; Tong R. H.; Qu F. Y. pH-sensitive gold nanorods with a mesoporous silica shell for drug release and photothermal therapy. Eur. J. Inorg. Chem. 2015, 2015, 2277–2284.Google Scholar
  91. [91]
    Zeiderman M. R.; Morgan D. E.; Christein J. D.; Grizzle W. E.; McMasters K. M.; McNally L. R. Acidic pH-targeted chitosan-capped mesoporous silica coated gold nanorods facilitate detection of pancreatic tumors via multispectral optoacoustic tomography. ACS Biomater. Sci. Eng. 2016, 2, 1108–1120.Google Scholar
  92. [92]
    Zhang Z. H.; Liu C. H.; Bai J. H.; Wu C. C.; Xiao Y.; Li Y. H.; Zheng J.; Yang R. H.; Tan W. H. Silver nanoparticle gated, mesoporous silica coated gold nanorods (AuNR@MS@AgNPs): Low premature release and multifunctional cancer theranostic platform. ACS Appl. Mater. Interfaces 2015, 7, 6211–6219.Google Scholar
  93. [93]
    Zhang Z. J.; Wang J.; Nie X.; Wen T.; Ji Y. L.; Wu X. C.; Zhao Y. L.; Chen C. Y. Near infrared laser-induced targeted cancer therapy using thermoresponsive polymer encapsulated gold nanorods. J. Am. Chem. Soc. 2014, 136, 7317–7326.Google Scholar
  94. [94]
    Baek S.; Singh R. K.; Kim T. H.; Seo J. W.; Shin U. S.; Chrzanowski W.; Kim H. W. Triple hit with drug carriers: pH- and temperature-responsive theranostics for multimodal chemo- and photothermal therapy and diagnostic applications. ACS Appl. Mater. Interfaces 2016, 8, 8967–8979.Google Scholar
  95. [95]
    An N.; Lin H. M.; Qu F. Y. Synthesis of a GNRs@mSiO2-ICGDOX@ Se-Se-FA nanocomposite for controlled chemo-/photothermal/photodynamic therapy. Eur. J. Inorg. Chem. 2018, 2018, 4375–4384.Google Scholar
  96. [96]
    Fang J.; Nakamura H.; Maeda H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv. Drug Delivery Rev. 2011, 63, 136–151.Google Scholar
  97. [97]
    Matsumoto Y.; Nichols J. W.; Toh K.; Nomoto T.; Cabral H.; Miura Y.; Christie R. J.; Yamada N.; Ogura T.; Kano M. R. et al. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery. Nat. Nanotechnol. 2016, 11, 533–538.Google Scholar
  98. [98]
    Shi J. J.; Kantoff P. W.; Wooster R.; Farokhzad O. C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2017, 17, 20–37.Google Scholar
  99. [99]
    Maeda H.; Wu J.; Sawa T.; Matsumura Y.; Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J. Control. Release 2000, 65, 271–284.Google Scholar
  100. [100]
    Danhier F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? J. Control. Release 2016, 244, 108–121.Google Scholar
  101. [101]
    Wilhelm S.; Tavares A. J.; Dai Q.; Ohta S.; Audet J.; Dvorak H. F.; Chan W. C. W. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 2016, 1, 16014.Google Scholar
  102. [102]
    Blanco E.; Shen H. F.; Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33, 941–951.Google Scholar
  103. [103]
    Huang P.; Bao L.; Zhang C. L.; Lin J.; Luo T.; Yang D. P.; He M.; Li Z. M.; Gao G.; Gao B. et al. Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photothermal therapy. Biomaterials 2011, 32, 9796–9809.Google Scholar
  104. [104]
    Luo G. F.; Chen W. H.; Lei Q.; Qiu W. X.; Liu Y. X.; Cheng Y. J.; Zhang X. Z. A triple-collaborative strategy for high-performance tumor therapy by multifunctional mesoporous silica-coated gold nanorods. Adv. Funct. Mater. 2016, 26, 4339–4350.Google Scholar
  105. [105]
    Andreev O. A.; Engelman D. M.; Reshetnyak Y. K. Targeting acidic diseased tissue: New technology based on use of the pH (Low) Insertion Peptide (pHLIP). Chim. Oggi 2009, 27, 34–37.Google Scholar
  106. [106]
    Xia H. X.; Yang X. Q.; Song J. T.; Chen J.; Zhang M. Z.; Yan D. M.; Zhang L.; Qin M. Y.; Bai L. Y.; Zhao Y. D. et al. Folic acid-conjugated silica-coated gold nanorods and quantum dots for dual-modality CT and fluorescence imaging and photothermal therapy. J. Mater. Chem. B 2014, 2, 1945–1953.Google Scholar
  107. [107]
    Lee C.; Hwang H. S.; Lee S.; Kim B.; Kim J. O.; Oh K. T.; Lee E. S.; Choi H. G.; Youn Y. S. Rabies virus-inspired silica-coated gold nanorods as a photothermal therapeutic platform for treating brain tumors. Adv. Mater. 2017, 29, 1605563.Google Scholar
  108. [108]
    Terentyuk G.; Panfilova E.; Khanadeev V.; Chumakov D.; Genina E.; Bashkatov A.; Tuchin V.; Bucharskaya A.; Maslyakova G.; Khlebtsov N. et al. Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo. Nano Res. 2014, 7, 325–337.Google Scholar
  109. [109]
    Monem A. S.; Elbialy N.; Mohamed N. Mesoporous silica coated gold nanorods loaded doxorubicin for combined chemo–photothermal therapy. Int. J. Pharm. 2014, 470, 1–7.Google Scholar
  110. [110]
    Wani A.; Savithra G. H. L.; Abyad A.; Kanvinde S.; Li J.; Brock S.; Oupický D. Surface PEGylation of mesoporous silica nanorods (MSNR): Effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells. Sci. Rep. 2017, 7, 2274.Google Scholar
  111. [111]
    Lee J.; Jeong C.; Kim W. J. Facile fabrication and application of near-IR light-responsive drug release system based on gold nanorods and phase change material. J. Mater. Chem. B 2014, 2, 8338–8345.Google Scholar
  112. [112]
    Song Z. X.; Liu Y.; Shi J.; Ma T.; Zhang Z.; Ma H.; Cao S. K. Hydroxyapatite/mesoporous silica coated gold nanorods with improved degradability as a multi-responsive drug delivery platform. Mater. Sci. Eng. C 2018, 83, 90–98.Google Scholar
  113. [113]
    Zhou H. M.; Xu H. X.; Li X.; Lv Y. H.; Ma T.; Guo S. Y.; Huang Z. J.; Wang X. B.; Xu P. H. Dual targeting hyaluronic acid-RGD mesoporous silica coated gold nanorods for chemo-photothermal cancer therapy. Mater. Sci. Eng. C 2017, 81, 261–270.Google Scholar
  114. [114]
    Khanal A.; Ullum C.; Kimbrough C. W.; Garbett N. C.; Burlison J. A.; McNally M. W.; Chuong P.; El-Baz A. S.; Jasinski J. B.; McNally L. R. Tumor targeted mesoporous silica-coated gold nanorods facilitate detection of pancreatic tumors using multispectral optoacoustic tomography. Nano Res. 2015, 8, 3864–3877.Google Scholar
  115. [115]
    Xu B. Y.; Ju Y.; Cui Y. B.; Song G. B.; Iwase Y.; Hosoi A.; Morita Y. tLyP-1–conjugated Au-nanorod@SiO2 core–shell nanoparticles for tumor-targeted drug delivery and photothermal therapy. Langmuir 2014, 30, 7789–7797.Google Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Carolina F. Rodrigues
    • 1
  • Telma A. Jacinto
    • 1
  • André F. Moreira
    • 1
  • Elisabete C. Costa
    • 1
  • Sónia P. Miguel
    • 1
  • Ilídio J. Correia
    • 1
    • 2
    Email author
  1. 1.CICS-UBI — Centro de Investigação em Ciências da SaúdeUniversidade da Beira InteriorCovilhãPortugal
  2. 2.CIEPQF — Departamento de Engenharia QuímicaUniversidade de CoimbraCoimbraPortugal

Personalised recommendations