Chemotherapy with Porous Silicon

  • Hélder A. SantosEmail author
Living reference work entry


The current cancer chemotherapy offered to patients still suffers from severe side effects to off-target cells. In the recent years, a plethora of studies using porous silicon (PSi) as a micro-/nanovector for specific drug delivery and imaging diagnostic tool have opened potential new avenues for the treatment of cancer diseases. In this context, PSi delivery systems that can specifically target cancer cells/tissues, precisely release the cargos, and even inducing immunostimulatory response for cancer immunotherapy, have also been demonstrated. PSi-based multifunctional systems encompassing both therapeutic and diagnostic functions have shown in real time the delivery of multi-payloads to the tumor site. In this chapter, the most recent selected PSi-based micro-/nanovectors for chemotherapy are reviewed and described. Relevant PSi formulations for chemotherapy are briefly summarized and the main results presented and discussed.


Drug Delivery Anticancer Drug Porous Silicon Endosomal Escape Blood Volume Fraction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Financial support from the Academy of Finland (decisions no. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013, grant no. 310892) are acknowledged.


  1. Alhmoud H, Delalat B, Elnathan R, Cifuentes-Rius A, Chaix A, Rogers M-L, Durand J-O, Voelcker NH (2015) Porous silicon nanodiscs for targeted drug delivery. Adv Funct Mater 25(7):1137–1145CrossRefGoogle Scholar
  2. Almeida PV, Shahbazi MA, Mäkilä E, Kaasalainen M, Salonen J, Hirvonen J, Santos HA (2014) Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors. Nanoscale 6(17):10377–10387CrossRefGoogle Scholar
  3. Bachelder EM, Beaudette TT, Broaders KE, Dashe J, Frechet JM (2008) Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications. J Am Chem Soc 130(32):10494–10495CrossRefGoogle Scholar
  4. Broaders KE, Cohen JA, Beaudette TT, Bachelder EM, Frechet JMJ (2009) Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy. Proc Natl Acad Sci U S A 106(14):5497–5502CrossRefGoogle Scholar
  5. Canham L, Santos HA, Palestino G (2015) Mesoporous biomaterials – multifunctional materials for future medical therapies and bioanalysis. Mesoporous Biomater 2(1):1–2CrossRefGoogle Scholar
  6. Edwards BK, Noone A-M, Mariotto AB, Simard EP, Boscoe FP, Henley SJ, Jemal A, Cho H, Anderson RN, Kohler BA, Eheman CR, Ward EM (2014) Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120(9):1290–1314CrossRefGoogle Scholar
  7. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D, Bray F (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6):1374–1403CrossRefGoogle Scholar
  8. Herranz-Blanco B, Arriaga LR, Mäkilä E, Correia A, Shrestha N, Mirza S, Weitz DA, Salonen J, Hirvonen J, Santos HA (2014) Microfluidic assembly of multistage porous silicon-lipid vesicles for controlled drug release. Lab Chip 14(6):1083–1086CrossRefGoogle Scholar
  9. Herranz-Blanco B, Liu D, Mäkilä E, Shahbazi M-A, Ginestar E, Zhang H, Aseyev V, Balasubramanian V, Salonen J, Hirvonen J, Santos HA (2015) On-chip self-assembly of a smart hybrid nanocomposite for antitumoral applications. Adv Funct Mater 25(10):1488–1497CrossRefGoogle Scholar
  10. Hong C, Lee J, Son M, Hong SS, Lee C (2011) In-vivo cancer cell destruction using porous silicon nanoparticles. Anticancer Drugs 22(10):971–977Google Scholar
  11. Kallinen AM, Sarparanta MP, Liu D, Mäkilä EM, Salonen JJ, Hirvonen JT, Santos HA, Airaksinen AJ (2014) In vivo evaluation of porous silicon and porous silicon solid lipid nanocomposites for passive targeting and imaging. Mol Pharm aceutics 11(8):2876–2886Google Scholar
  12. Kinnari PJ, Hyvönen ML, Mäkilä EM, Kaasalainen MH, Rivinoja A, Salonen JJ, Hirvonen JT, Laakkonen PM, Santos HA (2013) Tumour homing peptide-functionalized porous silicon nanovectors for cancer therapy. Biomaterials 34(36):9134–9141CrossRefGoogle Scholar
  13. Kong F, Zhang X, Zhang H, Qu X, Chen D, Servos M, Mäkilä E, Salonen J, Santos HA, Hai M, Weitz DA (2015) Inhibition of multidrug resistance of cancer cells by co-delivery of dna nanostructures and drugs using porous silicon nanoparticles@giant liposomes. Adv Funct Mater 25(22):3330–3340CrossRefGoogle Scholar
  14. Li X, Coffer JL, Chen Y, Pinizzotto RF, Newey J, Canham LT (1998) Transition metal complex-doped hydroxyapatite layers on porous silicon. J Am Chem Soc 120(45):11706–11709CrossRefGoogle Scholar
  15. Li X, St. John J, Coffer JL, Chen Y, Pinizzotto RF, Newey J, Reeves C, Canham LT (2000) Porosified silicon wafer structures impregnated with platinum anti-tumor compounds: fabrication, characterization, and diffusion studies. Biomed Microdevices 2(4):265–272CrossRefGoogle Scholar
  16. Liu D, Herranz-Blanco B, Mäkilä E, Arriaga LR, Mirza S, Weitz DA, Sandler N, Salonen J, Hirvonen J, Santos HA (2013a) Microfluidic templated mesoporous silicon-solid lipid microcomposites for sustained drug delivery. ACS Appl Mater Interfaces 5(22):12127–12134CrossRefGoogle Scholar
  17. Liu D, Mäkilä E, Zhang H, Herranz B, Kaasalainen M, Kinnari P, Salonen J, Hirvonen J, Santos HA (2013b) Nanostructured porous silicon-solid lipid nanocomposite: towards enhanced cytocompatibility and stability, reduced cellular association, and prolonged drug release. Adv Funct Mater 23(15):1893–1902CrossRefGoogle Scholar
  18. Liu D, Zhang H, Herranz-Blanco B, Mäkilä E, Lehto V-P, Salonen J, Hirvonen J, Santos HA (2014) Microfluidic assembly of monodisperse multistage ph-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery. Small 10(10):2029–2038CrossRefGoogle Scholar
  19. Liu D, Zhang H, Mäkilä E, Fan J, Herranz-Blanco B, Wang CF, Rosa R, Ribeiro AJ, Salonen J, Hirvonen J, Santos HA (2015) Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy. Biomaterials 39:249–259CrossRefGoogle Scholar
  20. Mäkilä E, Bimbo LM, Kaasalainen M, Herranz B, Airaksinen AJ, Heinonen M, Kukk E, Hirvonen J, Santos HA, Salonen J (2012) Amine modification of thermally carbonized porous silicon with silane coupling chemistry. Langmuir 28(39):14045–14054CrossRefGoogle Scholar
  21. Mi Y, Mu C, Wolfram J, Deng Z, Hu TY, Liu X, Blanco E, Shen H, Ferrari M (2016) A micro/nano composite for combination treatment of melanoma lung metastasis. Adv Healthc Mater 5(8):936–946CrossRefGoogle Scholar
  22. Mody HR (2011) Cancer nanotechnology: recent trends and developments. Int J Med Update – EJOURNAL 6(1).Google Scholar
  23. Neradil J, Pavlasova G, Veselska R (2012) New mechanisms for an old drug; DHFR- and non-DHFR-mediated effects of methotrexate in cancer cells. Klin Onkol 25(2):2S87–2S92Google Scholar
  24. Nie S (2010) Understanding and overcoming major barriers in cancer nanomedicine. Nanomedicine (Lond) 5(4):523–528CrossRefGoogle Scholar
  25. Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ (2011) Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small 7(14):2061–2069CrossRefGoogle Scholar
  26. Peng F, Cao Z, Ji X, Chu B, Su Y, He Y (2015) Silicon nanostructures for cancer diagnosis and therapy. Nanomedicine (Lond) 10(13):2109–2123CrossRefGoogle Scholar
  27. Perry MC, Doll DC, Freter CE (2012) Perry’s the chemotherapy source book, 5th edn. Wolters Kluwer, PhiladelphiaGoogle Scholar
  28. Riikonen J, Correia A, Kovalainen M, Näkki S, Lehtonen M, Leppanen J, Rantanen J, Xu W, Araújo F, Hirvonen J, Jarvinen K, Santos HA, Lehto VP (2015) Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib. Biomaterials 52:44–55CrossRefGoogle Scholar
  29. Ruoslahti E (2012) Peptides as targeting elements and tissue penetration devices for nanoparticles. Adv Mater 24(28):3747–3756CrossRefGoogle Scholar
  30. Saggar JK, Yu M, Tan Q, Tannock IF (2013) The tumor microenvironment and strategies to improve drug distribution. Front Oncol 3(154)Google Scholar
  31. Santos HA, Hirvonen J (2012) Nanostructured porous silicon materials: potential candidates for improving drug delivery. Nanomedicine (Lond) 7(9):1281–1284CrossRefGoogle Scholar
  32. Santos HA, Bimbo LM, Lehto VP, Airaksinen AJ, Salonen J, Hirvonen J (2011) Multifunctional porous silicon for therapeutic drug delivery and imaging. Curr Drug Discov Technol 8(3):228–249CrossRefGoogle Scholar
  33. Santos HA, Mäkilä E, Airaksinen AJ, Bimbo LM, Hirvonen J (2014) Porous silicon nanoparticles for nanomedicine: preparation and biomedical applications. Nanomedicine (Lond) 9(4):535–554CrossRefGoogle Scholar
  34. Savage DJ, Liu X, Curley SA, Ferrari M, Serda RE (2013) Porous silicon advances in drug delivery and immunotherapy. Curr Opin Pharmacol 13(5):834–841CrossRefGoogle Scholar
  35. Shahbazi MA, Herranz B, Santos HA (2012) Nanostructured porous Si-based nanoparticles for targeted drug delivery. Biomatter 2(4):296–312CrossRefGoogle Scholar
  36. Shahbazi M-A, Shrestha N, Mäkilä E, Araújo F, Correia A, Ramos T, Sarmento B, Salonen J, Hirvonen J, Santos HA (2014a) A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors. Nano Res 8(5):1505–1521CrossRefGoogle Scholar
  37. Shahbazi MA, Almeida PV, Mäkilä E, Correia A, Ferreira MP, Kaasalainen M, Salonen J, Hirvonen J, Santos HA (2014b) Poly(methyl vinyl ether-alt-maleic acid)-functionalized porous silicon nanoparticles for enhanced stability and cellular internalization. Macromol Rapid Commun 35(6):624–629CrossRefGoogle Scholar
  38. Shahbazi MA, Almeida PV, Mäkilä EM, Kaasalainen MH, Salonen JJ, Hirvonen JT, Santos HA (2014c) Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering. Biomaterials 35(26):7488–7500CrossRefGoogle Scholar
  39. Shen H, Rodriguez-Aguayo C, Xu R, Gonzalez-Villasana V, Mai J, Huang Y, Zhang G, Guo X, Bai L, Qin G, Deng X, Li Q, Erm DR, Aslan B, Liu X, Sakamoto J, Chavez-Reyes A, Han HD, Sood AK, Ferrari M, Lopez-Berestein G (2013) Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery. Clin Cancer Res 19(7):1806–1815CrossRefGoogle Scholar
  40. Skeel RT, Khlief SN (2011) Handbook of cancer chemotherapy, 8th edn. Lippincott Williams & Wilkins Handbook Series, PhiladelphiaGoogle Scholar
  41. Sutradhar KB, Amin ML (2014) Nanotechnology in cancer drug delivery and selective targeting. ISRN Nanotechnol 2014:12CrossRefGoogle Scholar
  42. Torchilin V (2011) Tumor delivery of macromolecular drugs based on the EPR effect. Adv Drug Deliv Rev 63(3):131–135CrossRefGoogle Scholar
  43. Varkouhi AK, Scholte M, Storm G, Haisma HJ (2011) Endosomal escape pathways for delivery of biologicals. J Control Release 151(3):220–228CrossRefGoogle Scholar
  44. Wang CF, Mäkilä EM, Kaasalainen MH, Liu D, Sarparanta MP, Airaksinen AJ, Salonen JJ, Hirvonen JT, Santos HA (2014) Copper-free azide-alkyne cycloaddition of targeting peptides to porous silicon nanoparticles for intracellular drug uptake. Biomaterials 35(4):1257–1266CrossRefGoogle Scholar
  45. Wang CF, Mäkilä EM, Bonduelle C, Rytkönen J, Raula J, Almeida S, Narvanen A, Salonen JJ, Lecommandoux S, Hirvonen JT, Santos HA (2015a) Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption. ACS Appl Mater Interfaces 7(3):2006–2015CrossRefGoogle Scholar
  46. Wang CF, Mäkilä EM, Kaasalainen MH, Hagström MV, Salonen JJ, Hirvonen JT, Santos HA (2015b) Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy. Acta Biomater 16:206–214CrossRefGoogle Scholar
  47. Wang CF, Sarparanta MP, Mäkilä EM, Hyvönen ML, Laakkonen PM, Salonen JJ, Hirvonen JT, Airaksinen AJ, Santos HA (2015c) Multifunctional porous silicon nanoparticles for cancer theranostics. Biomaterials 48:108–118CrossRefGoogle Scholar
  48. Wang Z, Kerketta R, Chuang YL, Dogra P, Butner JD, Brocato TA, Day A, Xu R, Shen H, Simbawa E, Al-Fhaid AS, Mahmoud SR, Curley SA, Ferrari M, Koay EJ, Cristini V (2016) Theory and experimental validation of a spatio-temporal model of chemotherapy transport to enhance tumor cell kill. PLoS Comput Biol 12(6):e1004969CrossRefGoogle Scholar
  49. WHO (2014) Cancer. Accessed 27th Oct 2014
  50. Wolfram J, Shen H, Ferrari M (2015) Multistage vector (MSV) therapeutics. J Control Release 219:406–415CrossRefGoogle Scholar
  51. Wu EC, Andrew JS, Cheng L, Freeman WR, Pearson L, Sailor MJ (2011) Real-time monitoring of sustained drug release using the optical properties of porous silicon photonic crystal particles. Biomaterials 32(7):1957–1966CrossRefGoogle Scholar
  52. Xia X, Mai J, Xu R, Perez JE, Guevara ML, Shen Q, Mu C, Tung HY, Corry DB, Evans SE, Liu X, Ferrari M, Zhang Z, Li XC, Wang RF, Shen H (2015) Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep 11(6):957–966CrossRefGoogle Scholar
  53. Xu R, Zhang G, Mai J, Deng X, Segura-Ibarra V, Wu S, Shen J, Liu H, Hu Z, Chen L, Huang Y, Koay E, Liu J, Ensor JE, Blanco E, Liu X, Ferrari M, Shen H (2016) An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat Biotechnol 34(4):414–418CrossRefGoogle Scholar
  54. Yokoi K, Godin B, Oborn CJ, Alexander JF, Liu X, Fidler IJ, Ferrari M (2013) Porous silicon nanocarriers for dual targeting tumor associated endothelial cells and macrophages in stroma of orthotopic human pancreatic cancers. Cancer Lett 334(2):319–327CrossRefGoogle Scholar
  55. Zhang H, Liu D, Shahbazi MA, Mäkilä E, Herranz-Blanco B, Salonen J, Hirvonen J, Santos HA (2014a) Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix. Adv Mater 26(26):4497–4503CrossRefGoogle Scholar
  56. Zhang M, Xu R, Xia X, Yang Y, Gu J, Qin G, Liu X, Ferrari M, Shen H (2014b) Polycation-functionalized nanoporous silicon particles for gene silencing on breast cancer cells. Biomaterials 35(1):423–431CrossRefGoogle Scholar
  57. Zhu J, Zheng L, Wen S, Tang Y, Shen M, Zhang G, Shi X (2014) Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles. Biomaterials 35(26):7635–7646CrossRefGoogle Scholar
  58. Zilony N, Tzur-Balter A, Segal E, Shefi O (2013) Bombarding cancer: biolistic delivery of therapeutics using porous Si carriers. Sci Rep 3:2499CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Division of Pharmaceutical Chemistry and Technology, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinland

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