Advertisement

Tunable Collagen Microfluidic Platform to Study Nanoparticle Transport in the Tumor Microenvironment

  • Matthew R. DeWittEmail author
  • M. Nichole Rylander
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1831)

Abstract

This chapter describes the motivation and protocol for creating a perfused 3D microfluidic in vitro platform representative of the tumor microenvironment to study nanoparticle transport. The cylindrical vascularized tumor platform described consists of a central endothelialized microchannel surrounded by a collagen hydrogel matrix containing cancer cells. This system can be employed to investigate key nanoparticle transport events in the tumor such as extravasation, diffusion within the extracellular matrix, and nanoparticle uptake. This easily manufactured tumor platform can be used for novel nanoparticle refinement focused on optimizing nanoparticle features such as size, shape, and functionalization method. This can yield ideal nanoparticles with properties that facilitate increased transport within the tumor microenvironment, leading to more effective nanoparticle-based treatments for cancer including nanoparticle-based drug delivery systems.

Key words

Tumor engineering Microfluidics Nanoparticle transport Tumor microenvironment Drug delivery 

Notes

Acknowledgments

Funding for this work was provided by the National Science Foundation Early CAREER Award CBET 0955072 and 0933571, the National Institutes of Health Grant R211R21CA158454-01A1. A special thanks to Rhys J Michna for his help in solidworks depictions of the 3D platform.

References

  1. 1.
    Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316CrossRefPubMedGoogle Scholar
  2. 2.
    Singh R, Lillard JW Jr (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Stover TC, Kim YS, Lowe TL, Kester M (2008) Thermoresponsive and biodegradable linear-dendritic nanoparticles for targeted and sustained release of a pro-apoptotic drug. Biomaterials 29:359–369CrossRefPubMedGoogle Scholar
  4. 4.
    Whitney J, DeWitt M, Whited BM, Carswell W, Simon A et al (2013) 3D viability imaging of tumor phantoms treated with single-walled carbon nanohorns and photothermal therapy. Nanotechnology 24:275102CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Carpin LB, Bickford LR, Agollah G, Yu TK, Schiff R et al (2011) Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells. Breast Cancer Res Treat 125:27–34CrossRefPubMedGoogle Scholar
  6. 6.
    Burke A, Ding X, Singh R, Kraft RA, Levi-Polyachenko N et al (2009) Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation. Proc Natl Acad Sci U S A 106:12897–12902CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hood RL, Carswell WF, Rodgers A, Kosoglu MA, Rylander MN et al (2013) Spatially controlled photothermal heating of bladder tissue through single-walled carbon nanohorns delivered with a fiberoptic microneedle device. Lasers Med Sci 28:1143–1150CrossRefPubMedGoogle Scholar
  8. 8.
    Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces 75:1–18CrossRefPubMedGoogle Scholar
  9. 9.
    Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102CrossRefPubMedGoogle Scholar
  10. 10.
    McBain SC, Yiu HH, Dobson J (2008) Magnetic nanoparticles for gene and drug delivery. Int J Nanomedicine 3:169–180PubMedPubMedCentralGoogle Scholar
  11. 11.
    Giustini AJ, Petryk AA, Cassim SM, Tate JA, Baker I et al (2010) Magnetic nanoparticle hyperthermia in Cancer treatment. Nano Life 1:01n02CrossRefGoogle Scholar
  12. 12.
    Kennedy LC, Bickford LR, Lewinski NA, Coughlin AJ, Hu Y et al (2011) A new era for cancer treatment: gold-nanoparticle-mediated thermal therapies. Small 7:169–183CrossRefPubMedGoogle Scholar
  13. 13.
    O'Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL (2004) Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett 209:171–176CrossRefPubMedGoogle Scholar
  14. 14.
    Loo C, Lowery A, Halas N, West J, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711CrossRefPubMedGoogle Scholar
  15. 15.
    Qin Z, Bischof JC (2012) Thermophysical and biological responses of gold nanoparticle laser heating. Chem Soc Rev 41:1191–1217CrossRefPubMedGoogle Scholar
  16. 16.
    Pekkanen AM, DeWitt MR, Rylander MN (2014) Nanoparticle enhanced optical imaging and phototherapy of cancer. J Biomed Nanotechnol 10:1677–1712CrossRefPubMedGoogle Scholar
  17. 17.
    Whitney JR, Sarkar S, Zhang J, Do T, Young T et al (2011) Single walled carbon nanohorns as photothermal cancer agents. Lasers Surg Med 43:43–51CrossRefPubMedGoogle Scholar
  18. 18.
    DeWitt MR, Pekkanen AM, Robertson J, Rylander CG, Nichole Rylander M (2014) Influence of hyperthermia on efficacy and uptake of carbon nanohorn-cisplatin conjugates. J Biomech Eng 136:021003CrossRefPubMedGoogle Scholar
  19. 19.
    Jain RK (1987) Transport of molecules across tumor vasculature. Cancer Metastasis Rev 6:559–593CrossRefPubMedGoogle Scholar
  20. 20.
    Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF (2010) Heterogeneity of the tumor vasculature. Semin Thromb Hemost 36:321–331CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284CrossRefPubMedGoogle Scholar
  22. 22.
    Hansen AE, Petersen AL, Henriksen JR, Boerresen B, Rasmussen P et al (2015) Positron emission tomography based elucidation of the enhanced permeability and retention effect in dogs with Cancer using Copper-64 liposomes. ACS Nano 9:6985–6995CrossRefPubMedGoogle Scholar
  23. 23.
    Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L et al (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A 95:4607–4612CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G et al (2000) Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 156:1363–1380CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA et al (1995) Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res 55:3752–3756PubMedGoogle Scholar
  26. 26.
    Kedem O, Katchalsky A (1958) Thermodynamic analysis of the permeability of biological membranes to non-electrolytes. Biochim Biophys Acta 27:229–246CrossRefPubMedGoogle Scholar
  27. 27.
    Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7:653–664CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Jain RK (1987) Transport of molecules in the tumor interstitium: a review. Cancer Res 47:3039–3051PubMedGoogle Scholar
  29. 29.
    Goel S, Duda DG, Xu L, Munn LL, Boucher Y et al (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91:1071–1121CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Baxter LT, Jain RK (1991) Transport of fluid and macromolecules in tumors. III. Role of binding and metabolism. Microvasc Res 41:5–23CrossRefPubMedGoogle Scholar
  31. 31.
    Baxter LT, Jain RK (1989) Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection. Microvasc Res 37:77–104CrossRefPubMedGoogle Scholar
  32. 32.
    Flessner MF, Choi J, Credit K, Deverkadra R, Henderson K (2005) Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors. Clin Cancer Res 11:3117–3125CrossRefPubMedGoogle Scholar
  33. 33.
    Adriani G, de Tullio MD, Ferrari M, Hussain F, Pascazio G et al (2012) The preferential targeting of the diseased microvasculature by disk-like particles. Biomaterials 33:5504–5513CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Decuzzi P, Godin B, Tanaka T, Lee SY, Chiappini C et al (2010) Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release 141:320–327CrossRefPubMedGoogle Scholar
  35. 35.
    Barua S, Mitragotri S (2014) Challenges associated with penetration of nanoparticles across cell and tissue barriers: a review of current status and future prospects. Nano Today 9:223–243CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Chithrani BD, Ghazani AA, Chan WC (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668CrossRefPubMedGoogle Scholar
  37. 37.
    Iversen TG, Skotland T, Sandvig K (2011) Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6:176–185CrossRefGoogle Scholar
  38. 38.
    Lazarovits J, Chen YY, Sykes EA, Chan WC (2015) Nanoparticle-blood interactions: the implications on solid tumour targeting. Chem Commun (Camb) 51:2756–2767CrossRefGoogle Scholar
  39. 39.
    Stirland DL, Nichols JW, Miura S, Bae YH (2013) Mind the gap: a survey of how cancer drug carriers are susceptible to the gap between research and practice. J Control Release 172:1045–1064CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Gao Y, Li M, Chen B, Shen Z, Guo P et al (2013) Predictive models of diffusive nanoparticle transport in 3-dimensional tumor cell spheroids. AAPS J 15:816–831CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Buchanan C, Rylander MN (2013) Microfluidic culture models to study the hydrodynamics of tumor progression and therapeutic response. Biotechnol Bioeng 110:2063–2072CrossRefPubMedGoogle Scholar
  42. 42.
    Szot CS, Buchanan CF, Freeman JW, Rylander MN (2011) 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials 32:7905–7912CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7:211–224CrossRefGoogle Scholar
  44. 44.
    Ghajar CM, Bissell MJ (2010) Tumor engineering: the other face of tissue engineering. Tissue Eng Part A 16:2153–2156CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Cross VL, Zheng Y, Won Choi N, Verbridge SS, Sutermaster BA et al (2010) Dense type I collagen matrices that support cellular remodeling and microfabrication for studies of tumor angiogenesis and vasculogenesis in vitro. Biomaterials 31:8596–8607CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Esch MB, King TL, Shuler ML (2011) The role of body-on-a-chip devices in drug and toxicity studies. Annu Rev Biomed Eng 13:55–72CrossRefPubMedGoogle Scholar
  47. 47.
    Verbridge SS, Chandler EM, Fischbach C (2010) Tissue-engineered three-dimensional tumor models to study tumor angiogenesis. Tissue Eng Part A 16:2147–2152CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sano MB, Arena CB, Bittleman KR, DeWitt MR, Cho HJ et al (2015) Bursts of bipolar microsecond pulses inhibit tumor growth. Sci Rep 5:14999CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Farahat WA, Wood LB, Zervantonakis IK, Schor A, Ong S et al (2012) Ensemble analysis of angiogenic growth in three-dimensional microfluidic cell cultures. PLoS One 7:e37333CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Sung KE, Yang N, Pehlke C, Keely PJ, Eliceiri KW et al (2011) Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects. Integr Biol (Camb) 3:439–450CrossRefGoogle Scholar
  51. 51.
    DelNero P, Song YH, Fischbach C (2013) Microengineered tumor models: insights & opportunities from a physical sciences-oncology perspective. Biomed Microdevices 15:583–593CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ng CP, Pun SH (2008) A perfusable 3D cell-matrix tissue culture chamber for in situ evaluation of nanoparticle vehicle penetration and transport. Biotechnol Bioeng 99:1490–1501CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kwak B, Ozcelikkale A, Shin CS, Park K, Han B (2014) Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip. J Control Release 194:157–167CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Buchanan CF, Voigt EE, Szot CS, Freeman JW, Vlachos PP et al (2014) Three-dimensional microfluidic collagen hydrogels for investigating flow-mediated tumor-endothelial signaling and vascular organization. Tissue Eng Part C Methods 20:64–75CrossRefPubMedGoogle Scholar
  55. 55.
    Buchanan CF, Verbridge SS, Vlachos PP, Rylander MN (2014) Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. Cell Adhes Migr 8:517–524CrossRefGoogle Scholar
  56. 56.
    Antoine EE, Vlachos PP, Rylander MN (2015) Tunable collagen I hydrogels for engineered physiological tissue micro-environments. PLoS One 10:e0122500CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Virginia Tech- Wake Forest School of Biomedical Engineering and SciencesBlacksburgUSA
  2. 2.Department of Mechanical EngineeringUniversity of Texas at AustinAustinUSA
  3. 3.Department of Biomedical EngineeringUniversity of Texas at AustinAustinUSA

Personalised recommendations