Surface Bioengineering of Diatom by Amine and Phosphate Groups for Efficient Drug Delivery

  • R. Sasirekha
  • P. Santhanam


The self-assembled existent biomaterials have been synthesized naturally with enormous three-dimensional structured porous with multifunctional properties (Sarikaya 1999). Diatoms are benthic photosynthetic brown algae, which is the most terrific living thing that can produce their exoskeleton with amorphous silica particles organically (Morse 1999; Sumper and Brunner 2006). Those outer shells arrayed with porous biosilica with distinctive 3D architecture, called frustules, with extremely organized pore structures, patterns of species and hierarchical arrangements with peculiar mechanical, molecular transport, ocular and bioluminescence properties (Parkinson and Gordon 1999; Lopez et al. 2005; Losic et al. 2009). Their biocompatibility and mechanical potency with humans and other species are highly prominent (Kröger and Poulsen 2008). The pores are displaying more dominancy on diatoms; hence the diatoms become smaller at each generation, even though the pore size remains same on diatom’s surface (Kröger and Poulsen 2008), so the identical pore size on diatom shell become a prospective biomaterial for the application of drug delivery. These features may well eradicate the low bioavailability of hydrophilic drugs and replace synthetic mesoporous silica materials as drug cargo loading (Lauritis 1968). Diatom frustules are available mainly as of two resources, including live diatom cultures with tiny amount of biomass and in the form of fossils diatomaceous earth (DE), in huge quantities. Owing to the silica chemistry of the diatom is having some limitations on those applications. Accordingly, to modify the biosilica material derived from diatoms, the significant efforts have recently been underwent technologically to convert it to be more suitable functional materials without disrupting the frustules morphologies and shapes. The conversion of biosilica into inorganic (MgO, TiO2, zeolites), semiconducting (Si–Ge), metal (Ag, Au) or organic (polyaniline) scaffolds has been demonstrated through several approaches including gas/solid displacement, chemical deposition, sol–gel synthesis and polymerization (Losic et al. 2007). The possible surface modification will generate new properties like localized surface plasmon (LSPR) and surface-enhanced Raman scattering (SERS) on diatom explored via simple mechanisms, which will have been generated from diatoms, functionalization with Au nanoparticles (Bao et al. 2009). The potency of drug cargo delivery from diatom biosilica through their nanoporous is proven by controlled drug releases. Diatom biosilica can also be modified with antibodies and enzymes (Gordon et al. 2009; Singh and Singh 2009; Downs Jr. et al. 2005). The impact of drug loading and release on surface functionalized diatom’s silica material, particularly investigating the properties of diatom surface and functionalization materials for both hydrophobic and hydrophilic drugs. The organosilanes and phosphonic acid such as 3-aminopropyltriethoxysilane [APTES] based self-assembled organic monolayers (SAM), N-(3-(trimethoxysilyl) propyl) ethylene diamine [AEAPTMS], 2-carboxyethyl-phosphonic acid [2-phos] were used for hydrophilic and 16-phosphono-hexadecanoic acid [16-phos] for hydrophobic drugs are used as chemical modifiers (Bariana et al. 2013a and Bariana et al. 2013b). Organosilanes APTES and AEAPTMS are amino functional groups containing amine modification agents and were mostly used for enhancing steady adsorption in numerous applications between organic compounds and silica substrates (Xu et al. 2003).



Authors thank the authorities of Bharathidasan University for providing the necessary facilities. Authors are thankful to the Department of Biotechnology, Govt. of India, New Delhi, for the provided microalgae culture facility through extramural project (BT/PR 5856/AAQ/3/598/2012). The first author thanks the DBT, Govt. of India, New Delhi, for fellowship provided.


  1. Aliabadi, H.S., M. Minaiyan, and A. Dabestan. 2010. Cytotoxic evaluation of doxorubicin in combination with simvastatin against human cancer cells. Research in Pharmaceutical Sciences 5 (2): 127–133.Google Scholar
  2. Aw, M.S., S. Simovic, Y. Yu, J. Addai-Mensah, and D. Losic. 2011. Silica microcapsules from diatoms as new carrier for delivery of therapeutics. Nanomedicine 6 (7): 1159–1173.CrossRefGoogle Scholar
  3. Aw, M.S., S. Simovic, Y. Yu, J. Addai-Mensah, and D. Losic. 2012. Porous silica microshells from diatoms as biocarrier for drug delivery applications. Powder Technology 223: 52–58.CrossRefGoogle Scholar
  4. Bae, M.K., S.H. Kim, J.W. Jeong, Y.M. Lee, H.S. Kim, S.R. Kim, I. Yun, S.K. Bae, and K.W. Kim. 2006. Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncology Reports 15: 1557–1562.Google Scholar
  5. Bao, Z., E.M. Ernst, S. Yoo, and K.H. Sandhage. 2009. Syntheses of porous self-supporting metal-nanoparticle assemblies with 3D morphologies inherited from biosilica templates (diatom frustules). Advanced Materials 21 (4): 474–478.CrossRefGoogle Scholar
  6. Bariana, M., M.S. Aw, and D. Losic. 2013a. Tailoring morphological and interfacial properties of diatom silica microparticles for drug delivery applications. Advanced Powder Technology 24: 757–763.CrossRefGoogle Scholar
  7. Bariana, M., M.S. Aw, M. Kurkuri, and D. Losic. 2013b. Tuning drug loading and release properties of diatom silica microparticles by surface modifications. International Journal of Pharmaceutics 443: 230–241.CrossRefGoogle Scholar
  8. Downs, L.S., Jr., L.M. Rogers, Y. Yokoyama, and S. Ramakrishnan. 2005. Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer. Gynecologic Oncology 98: 203–210.CrossRefGoogle Scholar
  9. Gordon, R., D. Losic, M.A. Tiffany, S.S. Nagy, and F.A.S. Sterrenburg. 2009. The glass menagerie: Diatoms for novel applications in nanotechnology. Trends in Biotechnology 27: 116–127.CrossRefGoogle Scholar
  10. Guillard, R.R.L., and J.H. Ryther. 1962. Studies of marine planktonic diatoms. I. Cyclotella nana Hustedt, and Detonulaconfervaceae (Cleve) Gran. Canadian Journal of Microbiology 8: 229–239.CrossRefGoogle Scholar
  11. Hansen, M.B., S.E. Nielsen, and K. Berg. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods 119: 203–210.CrossRefGoogle Scholar
  12. Hong, C.Y., Y. Yamauchi, and K.C.W. Wu. 2011. In vitro cytotoxicity and intracellular bioimaging of dendritic platinum nanoparticles by differential interference contrast. Chemisty Letters 40: 408–409.CrossRefGoogle Scholar
  13. Jani, A.M., E. Anglin, and S.J. McInnes. 2009. Fabrication of nanoporous anodic alumina membranes with layered surface chemistry. Chemical Communications 21: 3062–3064.Google Scholar
  14. Kröger, N., and N. Poulsen. 2008. Diatoms—From cell wall biogenesis to nanotechnology. Annual Review of Genetics 42: 83–107.CrossRefGoogle Scholar
  15. Lauritis, J.A. 1968. Studies on the biochemistry and fine structure of silicashell formation in diatoms IV. Fine structure of the apochloroticdiatom Nitzschiaalba Lewin and Lewin. Archives of Microbiology 62: 1–16.Google Scholar
  16. Lopez, P.J., J. Descles, and A.E. Allen. 2005. Prospects in diatom research. Current Opinion in Biotechnology 16: 180–186.CrossRefGoogle Scholar
  17. Losic, D., K. Short, J.G. Mitchell, R. Lal, and N.H. Voelcker. 2007. AFM nanoindentations of diatom biosilica surfaces. Langmuir 23 (9): 5014–5021.CrossRefGoogle Scholar
  18. Losic, D., J.G. Mitchell, and N.H. Voelcker. 2009. Diatomaceous lessons in nanotechnology and advanced materials. Advanced Materials 21: 2947–2958.CrossRefGoogle Scholar
  19. Malinauskas, R.A. 1997. Plasma hemoglobin measurement techniques for the in vitro evaluation of blood damage called by medical devices. Artificial Organs 21: 1255–1267.CrossRefGoogle Scholar
  20. Moradi, I., M. Behjati, and M. Kazemi. 2012. Application of anodized titanium for enhanced recruitment of endothelial progenitor cells. Nanoscale Research Letters 7: 298.CrossRefGoogle Scholar
  21. Morse, D.E. 1999. Silicon biotechnology: Harnessing biological silica production to construct new materials. Trends in Biotechnology 17: 230–232.CrossRefGoogle Scholar
  22. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65: 55–63.CrossRefGoogle Scholar
  23. Parkinson, J., and R. Gordon. 1999. Beyond micromachining: The potential of diatoms. Trends in Biotechnology 17: 190–196.CrossRefGoogle Scholar
  24. Perumal, P., P.B. Balaji, P. Santhanam, S. Ananth, A. Shenbaga Devi, and S. Dinesh Kumar. 2012. Isolation and culture of microalgae. In Manual on advances in aquaculture technology, ed. P. Santhanam, 166–181. Tiruchirappalli: Bharathidasan University.Google Scholar
  25. Rajiu, V., P. Balaji, T.S. Sheena, M.A. Akbarsha, and K. Jeganathan. 2015. Doxorubicin-anchored curcumin nanoparticles for multimode cancer treatment against human liver carcinoma cells. Particle and Particle Systems Characterization 32: 1028–1042.CrossRefGoogle Scholar
  26. Rosi, N.L., C.S. Thaxton, and C.A. Mirkin. 2004. Control of nanoparticle assembly by using DNA-modified diatom templates. Angewandte Chemie, International Edition 43: 5500–5503.CrossRefGoogle Scholar
  27. Sarikaya, M. 1999. Biomimetics: Materials fabrication through biology. Proceedings of the National Academy of Sciences of the United States of America 96: 14183–14185.CrossRefGoogle Scholar
  28. Singh, M., and N. Singh. 2009. Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells. Molecular and Cellular Biochemistry 325: 107–119.CrossRefGoogle Scholar
  29. Sumper, M., and E. Brunner. 2006. Learning from diatoms: Nature’s tools for the production of nanostructured silica. Advanced Functional Materials 16: 17–26.CrossRefGoogle Scholar
  30. Vallet-Regí, M., F. Balas, and D. Arcos. 2007. Mesoporous materials for drug delivery. Angewandte Chemie International Edition 46: 7548–7558.CrossRefGoogle Scholar
  31. Vrancken, K.C., K.P. Possemiers, and V.D. Voort. 1995. Surface modification of silica gels with aminoorganosilanes. Colloids and Surfaces: A 98 (3): 235–241.CrossRefGoogle Scholar
  32. Wang, F., H. Hui, T.J. Barnes, C. Barnett, and C.A. Prestidge. 2010. Oxidized mesoporous silicon microparticles for improved oral delivery of poorly soluble drugs. Molecular Pharmaceutics 7 (1): 227–236.CrossRefGoogle Scholar
  33. Xu, F., Y. Wang, and X. Wang. 2003. A novel hierarchical nanozeolite composite as sorbent for protein separation in immobilized metal-ion affinity chromatography. Advanced Materials 15 (20): 1751–1753.CrossRefGoogle Scholar
  34. Yoysungnoen, P., P. Wirachwong, C. Changtam, A. Suksamram, and S. Patumraj. 2008. Anticancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice. World Journal of Gastroenterology 14: 2003–2009.CrossRefGoogle Scholar
  35. Zhang, H., M.A. Shahbazi, and E.M. Mkila. 2013. Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine. Biomaterials 34: 9210–9219.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • R. Sasirekha
    • 1
  • P. Santhanam
    • 1
  1. 1.Marine Planktonology & Aquaculture Laboratory, Department of Marine Science, School of Marine SciencesBharathidasan UniversityTiruchirappalliIndia

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